Report title

THE TREATMENT OF SYMPTOMATIC
OSTEOPOROTIC SPINAL COMPRESSION
FRACTURES
GUIDELINE AND EVIDENCE REPORT
Adopted by the American Academy of Orthopaedic Surgeons
Board of Directors
September 24, 2010
AAOS Clinical Practice Guidelines Unit Disclaimer
This Clinical Practice Guideline was developed by an AAOS physician volunteer Work
Group based on a systematic review of the current scientific and clinical information and
accepted approaches to treatment and/or diagnosis. This Clinical Practice Guideline is not
intended to be a fixed protocol, as some patients may require more or less treatment or
different means of diagnosis. Clinical patients may not necessarily be the same as those
found in a clinical trial. Patient care and treatment should always be based on a
clinician's independent medical judgment, given the individual patient's clinical
circumstances.
Disclosure Requirement
In accordance with AAOS policy, all individuals whose names appear as authors or
contributors to Clinical Practice Guideline filed a disclosure statement as part of the
submission process. All panel members provided full disclosure of potential conflicts of
interest prior to voting on the recommendations contained within this Clinical Practice
Guidelines.
Funding Source
This Clinical Practice Guideline was funded exclusively by the American Academy of
Orthopaedic Surgeons who received no funding from outside commercial sources to
support the development of this document.
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Some drugs or medical devices referenced or described in this Clinical Practice Guideline
may not have been cleared by the Food and Drug Administration (FDA) or may have
been cleared for a specific use only. The FDA has stated that it is the responsibility of the
physician to determine the FDA clearance status of each drug or device he or she wishes
to use in clinical practice.
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from the AAOS.
Published 2010 by the American Academy of Orthopaedic Surgeons 6300 North River Road Rosemont, IL 60018 First Edition Copyright 2010 by the American Academy of Orthopaedic Surgeons AAOS Clinical Practice Guidelines Unit Summary of Recommendations
The following is a summary of the recommendations in the AAOS' clinical practice guideline, The Treatment of Symptomatic Osteoporotic Spinal Compression fractures. This summary does not contain rationales that explain how and why these recommendations were developed nor does it contain the evidence supporting these recommendations. All readers of this summary are strongly urged to consult the full guideline and evidence report for this information. We are confident that those who read the full guideline and evidence report will see that the recommendations were developed using systematic evidence-based processes designed to combat bias, enhance transparency, and promote reproducibility. This summary of recommendations is not intended to stand alone. Treatment decisions should be made in light of all circumstances presented by the patient. Treatments and procedures applicable to the individual patient rely on mutual communication between patient, physician, and other healthcare practitioners. 1. We suggest patients who present with an osteoporotic spinal compression fracture on imaging with correlating clinical signs and symptoms suggesting an acute injury (0-5 days after identifiable event or onset of symptoms) and who are neurologically intact be treated with calcitonin for 4 weeks. Strength of Recommendation: Moderate Description: Evidence from two or more "Moderate" strength studies with consistent findings, or evidence
from a single "High" quality study for recommending for or against the intervention. A Moderate
recommendation means that the benefits exceed the potential harm (or that the potential harm clearly exceeds
the benefits in the case of a negative recommendation), but the strength of the supporting evidence is not as
strong.
Implications: Practitioners should generally follow a Moderate recommendation but remain alert to new
information and be sensitive to patient preferences.
2. Ibandronate and strontium ranelate are options to prevent additional symptomatic fractures in patients who present with an osteoporotic spinal compression fracture on imaging with correlating clinical signs and symptoms. Strength of Recommendation: Limited Description: Evidence from two or more "Low" strength studies with consistent findings, or evidence from a
single "Moderate" quality study recommending for or against the intervention or diagnostic. A Limited
recommendation means the quality of the supporting evidence that exists is unconvincing, or that well-
conducted studies show little clear advantage to one approach versus another.
Implications: Practitioners should exercise clinical judgment when following a recommendation classified as
Limited, and should be alert to emerging evidence that might negate the current findings. Patient preference
should have a substantial influencing role.
AAOS Clinical Practice Guidelines Unit 3. We are unable to recommend for or against bed rest, complementary and alternative medicine, or opioids/analgesics for patients who present with an osteoporotic spinal compression fracture on imaging with correlating clinical signs and symptoms and who are neurologically intact. Strength of Recommendation: Inconclusive Description: Evidence from a single low quality study or conflicting findings that do not allow a
recommendation for or against the intervention. An Inconclusive recommendation means that there is a lack
of compelling evidence resulting in an unclear balance between benefits and potential harm.
Implications: Practitioners should feel little constraint in following a recommendation labeled as
Inconclusive, exercise clinical judgment, and be alert for emerging evidence that clarifies or helps to
determine the balance between benefits and potential harm. Patient preference should have a substantial
influencing role.
4. It is an option to treat patients who present with an osteoporotic spinal compression fracture at L3 or L4 on imaging with correlating clinical signs and symptoms suggesting an acute injury and who are neurologically intact with an L2 nerve root block. Strength of Recommendation: Limited Description: Evidence from two or more "Low" strength studies with consistent findings, or evidence from a
single "Moderate" quality study recommending for or against the intervention or diagnostic. A Limited
recommendation means the quality of the supporting evidence that exists is unconvincing, or that well-
conducted studies show little clear advantage to one approach versus another.
Implications: Practitioners should exercise clinical judgment when following a recommendation classified as
Limited, and should be alert to emerging evidence that might negate the current findings. Patient preference
should have a substantial influencing role.
5. We are unable to recommend for or against treatment with a brace for patients who present with an osteoporotic spinal compression fracture on imaging with correlating clinical signs and symptoms and who are neurologically intact. Strength of Recommendation: Inconclusive Description: Evidence from a single low quality study or conflicting findings that do not allow a
recommendation for or against the intervention. An Inconclusive recommendation means that there is a lack
of compelling evidence resulting in an unclear balance between benefits and potential harm.
Implications: Practitioners should feel little constraint in following a recommendation labeled as
Inconclusive, exercise clinical judgment, and be alert for emerging evidence that clarifies or helps to
determine the balance between benefits and potential harm. Patient preference should have a substantial
influencing role.
AAOS Clinical Practice Guidelines Unit 6. We are unable to recommend for or against a supervised or unsupervised exercise program for patients who present with an osteoporotic spinal compression fracture on imaging with correlating clinical signs and symptoms and who are neurologically intact. Strength of Recommendation: Inconclusive Description: Evidence from a single low quality study or conflicting findings that do not allow a
recommendation for or against the intervention. An Inconclusive recommendation means that there is a lack
of compelling evidence resulting in an unclear balance between benefits and potential harm.
Implications: Practitioners should feel little constraint in following a recommendation labeled as
Inconclusive, exercise clinical judgment, and be alert for emerging evidence that clarifies or helps to
determine the balance between benefits and potential harm. Patient preference should have a substantial
influencing role.
7. We are unable to recommend for or against electrical stimulation for patients who present with an osteoporotic spinal compression fracture on imaging with correlating clinical signs and symptoms and who are neurologically intact. Strength of Recommendation: Inconclusive Description: Evidence from a single low quality study or conflicting findings that do not allow a
recommendation for or against the intervention. An Inconclusive recommendation means that there is a lack
of compelling evidence resulting in an unclear balance between benefits and potential harm.
Implications: Practitioners should feel little constraint in following a recommendation labeled as
Inconclusive, exercise clinical judgment, and be alert for emerging evidence that clarifies or helps to
determine the balance between benefits and potential harm. Patient preference should have a substantial
influencing role.
8. We recommend against vertebroplasty for patients who present with an osteoporotic spinal compression fracture on imaging with correlating clinical signs and symptoms and who are neurologically intact. Strength of Recommendation: Strong Description: Evidence is based on two or more "High" strength studies with consistent findings for
recommending for or against the intervention. A Strong recommendation means that the benefits of the
recommended approach clearly exceed the potential harm (or that the potential harm clearly exceeds the
benefits in the case of a strong negative recommendation), and that the strength of the supporting evidence is
high.
Implications: Practitioners should follow a Strong recommendation unless a clear and compelling rationale
for an alternative approach is present.
AAOS Clinical Practice Guidelines Unit 9. Kyphoplasty is an option for patients who present with an osteoporotic spinal compression fracture on imaging with correlating clinical signs and symptoms and who are neurologically intact. Strength of Recommendation: Limited Description: Evidence from two or more "Low" strength studies with consistent findings, or evidence from a
single "Moderate" quality study recommending for or against the intervention or diagnostic. A Limited
recommendation means the quality of the supporting evidence that exists is unconvincing, or that well-
conducted studies show little clear advantage to one approach versus another.
Implications: Practitioners should exercise clinical judgment when following a recommendation classified as
Limited, and should be alert to emerging evidence that might negate the current findings. Patient preference
should have a substantial influencing role.
10. We are unable to recommend for or against improvement of kyphosis angle in the treatment of patients who present with an osteoporotic spinal compression fracture on imaging with correlating clinical signs and symptoms. Strength of Recommendation: Inconclusive Description: Evidence from a single low quality study or conflicting findings that do not allow a
recommendation for or against the intervention. An Inconclusive recommendation means that there is a lack
of compelling evidence resulting in an unclear balance between benefits and potential harm.
Implications: Practitioners should feel little constraint in following a recommendation labeled as
Inconclusive, exercise clinical judgment, and be alert for emerging evidence that clarifies or helps to
determine the balance between benefits and potential harm. Patient preference should have a substantial
influencing role.
11. We are unable to recommend for or against any specific treatment for patients who present with an osteoporotic spinal compression fracture on imaging with correlating clinical signs and symptoms and who are not neurologically intact. Strength of Recommendation: Inconclusive Description: Evidence from a single low quality study or conflicting findings that do not allow a
recommendation for or against the intervention. An Inconclusive recommendation means that there is a lack
of compelling evidence resulting in an unclear balance between benefits and potential harm.
Implications: Practitioners should feel little constraint in following a recommendation labeled as
Inconclusive, exercise clinical judgment, and be alert for emerging evidence that clarifies or helps to
determine the balance between benefits and potential harm. Patient preference should have a substantial
influencing role.
AAOS Clinical Practice Guidelines Unit Work Group

Stephen I Esses, MD, Chair
Seattle, WA 98105 Southwest Orthopedic Group 6560 Fannin St Ste 1016 Evidence Based Practice Committee Chair Houston TX 77030-2761 Michael Keith, MD
2500 Metro Health Drive Robert McGuire, MD, Vice-Chair
Cleveland, OH 44109-1900 University of Mississippi Medical Center Department of Orthopedic Surgery AAOS Staff: Charles M. Turkelson, PhD
Jackson MS 39216-4500 Director of Research and Scientific Affairs 6300 N. River Rd, Suite 503 John Jenkins, MD
Rosemont, IL 60018 University of Mississippi Medical Center Division of Rheumatology, Dept of Janet L. Wies, MPH
AAOS Clinical Practice Guideline Manager Jackson MS 39216-4500 Patrick Sluka, MPH
AAOS Research Analyst Joel Finkelstein, MD
2075 Bayview Ave MG361 Kevin M. Boyer
Toronto ON M4N3M AAOS Research Analyst Eric Woodard, MD
Kristin Hitchcock, MLS
New England Baptist Hospital AAOS Medical Librarian 125 Parker Hill Ave. Special Acknowledgements Sara Anderson, MPH Guidelines and Technology Oversight Chair Laura Raymond, MA William C. Watters III MD
6624 Fannin #2600 Houston, TX 77030 Guidelines and Technology Oversight Vice-Chair Michael J. Goldberg, MD
Department of Orthopaedics Seattle Children's Hospital 4800 Sand Point Way NE AAOS Clinical Practice Guidelines Unit Peer Review
Participation in the AAOS peer review process does not constitute an endorsement
of this guideline by the participating organization.
The following seven organizations participated in peer review of this clinical practice guideline and gave their explicit consent to have their names listed in this document: American Academy of Physical Medicine and Rehabilitation (AAPMR)
American Association of Neurological Surgeons/Congress of Neurological Surgeons
(AANS/CNS Joint Section)
American College of Radiology (ACR)
AO Spine International
International Spine Intervention Society (ISIS)
National Osteoporosis Foundation (NOF)
North American Spine Association (NASS)
Participation in the AAOS peer review process does not constitute an endorsement
of this guideline by the participating organization.
AAOS Clinical Practice Guidelines Unit Table of Contents
AAOS Clinical Practice Guidelines Unit AAOS Clinical Practice Guidelines Unit AAOS Clinical Practice Guidelines Unit AAOS Clinical Practice Guidelines Unit List of Figures
AAOS Clinical Practice Guidelines Unit List of Tables
AAOS Clinical Practice Guidelines Unit AAOS Clinical Practice Guidelines Unit AAOS Clinical Practice Guidelines Unit I. INTRODUCTION
OVERVIEW
This clinical practice guideline is based on a systematic review of published studies on
the treatment of symptomatic osteoporotic spinal compression fractures in adults. In
addition to providing practice recommendations, this guideline also highlights gaps in the
literature and areas that require future research.
This guideline is intended to be used by all appropriately trained surgeons and all qualified physicians managing the treatment of symptomatic osteoporotic spinal compression fractures. It is also intended to serve as an information resource for decision makers and developers of practice guidelines and recommendations. GOALS AND RATIONALE
The purpose of this clinical practice guideline is to help improve treatment based on the
current best evidence. Current evidence-based medicine (EBM) standards demand that
physicians use the best available evidence in their clinical decision making. To assist in
this, this clinical practice guideline consists of a systematic review of the available
literature regarding the treatment of symptomatic osteoporotic spinal compression
fractures. The systematic review detailed herein was conducted between March 2009 and
February 2010 and demonstrates where there is good evidence, where evidence is
lacking, and what topics future research must target in order to improve the treatment of
patients with symptomatic osteoporotic spinal compression fractures. AAOS staff and the
physician work group systematically reviewed the available literature and subsequently
wrote the following recommendations based on a rigorous, standardized process.
Musculoskeletal care is provided in many different settings by many different providers. We created this guideline as an educational tool to guide qualified physicians through a series of treatment decisions in an effort to improve the quality and efficiency of care. This guideline should not be construed as including all proper methods of care or excluding methods of care reasonably directed to obtaining the same results. The ultimate judgment regarding any specific procedure or treatment must be made in light of all circumstances presented by the patient and the needs and resources particular to the locality or institution. INTENDED USERS
This guideline is intended to be used by orthopaedic surgeons and all qualified physicians
managing patients with symptomatic osteoporotic spinal compression fractures.
Typically, orthopaedic surgeons will have completed medical training, a qualified
residency in orthopaedic surgery, and some may have completed additional sub-specialty
training. Insurance payers, governmental bodies, and health-policy decision-makers may
also find this guideline useful as an evolving standard of evidence regarding treatment of
symptomatic osteoporotic spinal compression fractures.
AAOS Clinical Practice Guidelines Unit Treatment for symptomatic osteoporotic spinal compression fractures is based on the assumption that decisions are predicated on patient and physician mutual communication with discussion of available treatments and procedures applicable to the individual patient. Once the patient has been informed of available therapies and has discussed these options with his/her physician, an informed decision can be made. Clinician input based on experience with conservative management and the clinician's surgical experience and skills increases the probability of identifying patients who will benefit from specific treatment options. PATIENT POPULATION
This document addresses the treatment of symptomatic osteoporotic spinal compression
fractures in adults (defined as patients 18 years of age and older).
ETIOLOGY
Symptomatic osteoporotic spinal compression fractures are a result of osteoporosis.
INCIDENCE
Symptomatic osteoporotic spinal compression fractures are a common occurrence. About
750,000 new vertebral fractures occur each year in the United States.1
BURDEN OF DISEASE
The economic burden of treating incident osteoporotic fractures was estimated at $17
billion in 2005.2
EMOTIONAL AND PHYSICAL IMPACT
Symptomatic osteoporotic spinal compression fractures cause pain, loss of physical
function, and are associated with increased mortality.
POTENTIAL BENEFITS, HARMS, AND CONTRAINDICATIONS
The aim of treatment is pain relief and recovery of mobility. Most treatments are
associated with some known risks, especially invasive and operative treatments. In
addition, contraindications vary widely based on the treatment administered. Therefore,
discussion of available treatments and procedures applicable to the individual patient rely
on mutual communication between the patient and physician, weighing the potential risks
and benefits for that patient.
AAOS Clinical Practice Guidelines Unit II. METHODS
This clinical practice guideline and the systematic review upon which it is based evaluate the effectiveness of treatments for symptomatic osteoporotic spinal compression fractures. This section describes the methods used to prepare this guideline and systematic review, including search strategies used to identify literature, criteria for selecting eligible articles, determining the strength of the evidence, data extraction, methods of statistical analysis, and the review and approval of the guideline. The methods used to perform this systematic review were employed to minimize bias in the selection, appraisal, and analysis of the available evidence.3, 4 These processes are vital to the development of reliable, transparent, and accurate clinical recommendations for treating symptomatic osteoporotic spinal compression fractures. This guideline and systematic review were prepared by the AAOS Treatment of Symptomatic Osteoporotic Spinal Compression Fractures guideline work group with the assistance of the AAOS Clinical Practice Guidelines Unit in the Department of Research and Scientific Affairs at the AAOS . To develop this guideline, the work group held an introductory meeting to develop the scope of the guideline on March 28, 2009. Upon completion of the systematic review, the work group met again on February 27 and 28, 2010 to write and vote on the final recommendations and rationales for each recommendation. The resulting draft guidelines were then peer-reviewed, subsequently sent for public commentary, and then sequentially approved by the AAOS Evidence Based Practice Committee, AAOS Guidelines and Technology Oversight Committee, AAOS Council on Research, Quality Assessment, and Technology, and the AAOS Board of Directors (seefor a description of the AAOS bodies involved in the approval process) FORMULATING PRELIMINARY RECOMMENDATIONS
The work group began work on this guideline by constructing a set of preliminary
recommendations. These recommendations specify [what] should be done in [whom],
[when], [where], and [how often or how long]. They function as questions for the
systematic review, not as final recommendations or conclusions. Preliminary
recommendations are almost always modified on the basis of the results of the systematic
review. Once established, these a priori preliminary recommendations cannot be
modified until the final work group meeting, they must be addressed by the systematic
review, and the relevant review results must be presented in the final guideline.
STUDY SELECTION CRITERIA
We developed a priori article inclusion criteria for our review. These criteria are our
"rules of evidence" and articles that do not meet them are, for the purposes of this
guideline, not evidence.
To be included in our systematic reviews (and hence, in this guideline) an article had to be a report of a study that: AAOS Clinical Practice Guidelines Unit Investigates osteoporotic spinal compression fracture patients • is a full article report of a clinical study (i.e., retrospective case series, medical records review, meeting abstracts, historical articles, editorials, letters, and commentaries are excluded) • was published in English • was published in or after 1966 • appeared in a peer-reviewed publication • enrolled 10 or more patients per group • presented results quantitatively • enrolled patients 18 years of age or older (100% of study population) • is not an in vitro, biomechanical, or cadaver study • excluded the following patients (unless results were reported separately): osteogenesis imperfecta (OI) solid metastatic tumors of the spine • for any given follow-up time point in any included study, there must be ≥ 50% patient follow-up (if the follow-up is >50% but <80%, the study quality will be downgraded by one Level) • results reported as "post-hoc subgroup analyses" will be excluded 5 When a study's "duration of symptoms" is not the same as those examined by the work group (i.e. 0-2 weeks, 2-6 weeks, etc.) the study will be assigned to the appropriate "duration of symptoms" group based upon the mean duration of symptoms. If a range rather than mean is provided, the higher end of the range will dictate which "duration of symptoms" group the study will be assigned to. For example, a study reporting patient symptoms of 0-4 weeks would be included in the time frame "2-6 weeks" created by the work group. When considering studies for inclusion, we included only the best available evidence. Accordingly, we first included Level I evidence. In the absence of two or more studies of this Level, we sequentially searched for and included Level II through Level IV evidence, and did not proceed to a lower level if there were two or more studies of a higher level. For example, if there were two Level II studies that addressed a recommendation, we did not include Level III or IV studies. AAOS Clinical Practice Guidelines Unit OUTCOMES CONSIDERED
Clinical studies often report many different outcomes. For this guideline, patient-oriented
outcomes are included wherever possible. If patient-oriented outcomes were not available
surrogate/intermediate outcomes were considered. Surrogate outcome measures are
laboratory measurements or another physical sign used as substitutes for a clinically
meaningful end point that measures directly how a patient feels, functions, or survives.6
Radiographic results are an example of a surrogate outcome.
For outcomes measured using "paper and pencil" instruments (e.g. the visual analogue scale), the results using validated instruments are considered the best available evidence. In the absence of results using validated instruments, results using non-validated instruments are considered as the best available evidence and the strength of the recommendation is lowered. For this guideline, all outcomes we reported were validated in a spine patient population. MINIMAL CLINICALLY IMPORTANT IMPROVEMENT
Wherever possible, we considered the effects of treatments in terms of the minimal
clinically important improvement (MCII) in addition to whether their effects were
statistically significant. The MCII is the smallest clinical change that is important to
patients, and recognizes the fact that there are some treatment-induced statistically
significant improvements that are too small to matter to patients. The values we used for
MCIIs are derived from a published study investigating the Visual Analogue Scale, the
Numerical Rating Scale, the Oswestry Disability Index, and the Roland Disability
Questionnaire;7 a study investigating the Physical Component Summary of the SF-36;8 a
study investigating the Assessment of Quality of Life instrument (AQoL);9 and a study
investigating the EQ-5D instrument.10
Table 1 MCII of outcomes
Outcome Measure
(points)
Pain – VAS (0-100) Pain – NRS (0-10) Oswestry Disability Index Roland-Morris Disability SF-36 Physical Component AAOS Clinical Practice Guidelines Unit When possible we describe the results of studies using terminology based on that of Armitage, et al.11 The associated descriptive terms in this guideline and the conditions for using each of these terms, are outlined in Table 2 Descriptive terms for results with MCII
Descriptive Term
Condition for Use
Statistically significant and Clinically Important lower confidence limit > MCII Statistically significant and Possibly Clinically Important confidence intervals contain the MCII Statistically significant and Not Clinically Important upper confidence limit < MCII Not statistically significant and upper confidence limit < MCII Not statistically significant but confidence intervals contain the MCII When MCII values from the specific guideline patient population was not available, we used values from the most closely related population that has published data available. We acknowledge that there can be variance in the MCII from disease to disease as well as what individual patients consider improvement. For this guideline, we included MCII values for pain and disability from studies including patients with low back pain, the MCII values cited for the SF-36 PCS are derived from patients who were treated with lumbar spine surgery and the MCII for the quality of life values are from studies that included a variety of conditions.7,8,9,10 LITERATURE SEARCHES
We attempted to make our searches for articles comprehensive. Using comprehensive
literature searches ensures that the evidence we considered for this guideline is not biased
for (or against) any particular point of view.
We searched for articles published from January 1966 to December 31, 2009. We searched four electronic databases; PubMed, EMBASE, CINAHL, and The Cochrane Central Register of Controlled Trials. Strategies for searching electronic databases were constructed by a Medical Librarian using previously published search strategies to identify relevant studies.12-18 We supplemented searches of electronic databases with manual screening of the bibliographies of all retrieved publications. We also searched the bibliographies of recent systematic reviews and other review articles for potentially relevant citations. Finally, work group members provided a list of potentially relevant studies that were not identified by our searches. All articles identified were subject to the study selection criteria listed above. AAOS Clinical Practice Guidelines Unit The study attrition diagram inprovides details about the inclusion and exclusion of the studies considered for this guideline. The search strategies used to identify these studies are provided i DATA EXTRACTION
Data elements extracted from studies were defined in consultation with the physician
work group. The elements extracted are shown i Evidence tables were
constructed to summarize the best evidence pertaining to each preliminary
recommendation. Disagreements about the accuracy of extracted data were resolved by
consensus and consulting the work group.
JUDGING THE QUALITY OF EVIDENCE
Determining the quality of the included evidence is vitally important when preparing any
evidence-based work product. Doing so conveys the amount of confidence one can have
in any study's results. One has more confidence in high quality evidence than in low
quality evidence.
Assigning a level of evidence on the basis of study design plus other quality characteristics ties the levels of evidence we report more closely to quality than levels of evidence based only on study design. Because we tie quality to levels of evidence, we are able to characterize the confidence one can have in their results. Accordingly, we characterize the confidence one can have in Level I evidence as high, the confidence one can have in Level II and III evidence as moderate, and the confidence one can have in Level IV and V evidence as low. Similarly, throughout the guideline we refer to Level I evidence as reliable, Level II and III evidence as moderately reliable, and Level IV and V evidence as not reliable. TREATMENT STUDIES
In studies investigating the result of treatment, we assessed the quality of the evidence for each outcome at each time point reported in a study. We did not simply assess the overall quality of a study. Our approach follows the recommendations of the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) working group19 as well as others.20 We evaluated quality on a per outcome basis rather than a per study basis because quality is not necessarily the same for all outcomes and all follow-up times reported in a study. For example, a study might report results immediately after patients received a given treatment and after some period of time has passed. Often, nearly all enrolled patients contribute data at early follow-up times but, at much later follow-up times, only a few patients may contribute data. One has more confidence in the earlier data than in the later data. The fact that we would assign a higher quality score to the earlier results reflects this difference in confidence. We assessed the quality of treatment studies using a two step process. First, we assigned a level of evidence to all results reported in a study based solely on that study's design. Accordingly, all data presented in randomized controlled trials were initially categorized as Level I evidence, all results presented in non-randomized controlled trials and other AAOS Clinical Practice Guidelines Unit prospective comparative studies were initially categorized as Level II, all results presented in retrospective comparative and case-control studies were initially categorized as Level III, and all results presented in prospective case-series reports were initially categorized as Level IV. We next assessed each outcome at each reported time point using a quality questionnaire and, when quality standards were not met, downgraded the level of evidence (for this outcome at this time point) by one level (see DEFINING THE STRENGTH OF THE RECOMMENDATIONS
Judging the quality of evidence is only a stepping stone towards arriving at the strength
of a guideline recommendation. Unlike Levels of Evidence (which apply only to a given
result at a given follow-up time in a given study) strength of recommendation takes into
account the quality, quantity, and applicability of the available evidence. Strength also
takes into account the trade-off between the benefits and harms of a treatment or
diagnostic procedure, and the magnitude of a treatment's effect.
Strength of recommendation expresses the degree of confidence one can have in a recommendation. As such, the strength expresses how possible it is that a recommendation will be overturned by future evidence. It is very difficult for future evidence to overturn a recommendation that is based on many high quality randomized controlled trials that show a large effect. It is much more likely that future evidence will overturn recommendations derived from a few small case series. Consequently, recommendations based on the former kind of evidence are given a high strength of recommendation and recommendations based on the latter kind of evidence are given a low strength. To develop the strength of a recommendation, AAOS staff first assigned a preliminary strength for each recommendation that took only the quality and quantity of the available evidence into account (see. Work group members then modified the preliminary strength using the ‘Form for Assigning Strength of Recommendation (Interventions)' shown in AAOS Clinical Practice Guidelines Unit Table 3 Strength of Recommendation Descriptions
Statement
Description of Evidence Strength
Implication for Practice
Evidence is based on two or more "High" strength studies Practitioners should follow a Strong
with consistent findings for recommending for or against the recommendation unless a clear and compelling rationale for an alternative approach is present.
A Strong recommendation means that the benefits of the
recommended approach clearly exceed the potential harm (or
that the potential harm clearly exceeds the benefits in the case
of a strong negative recommendation), and that the strength
of the supporting evidence is high.
Moderate
Evidence from two or more "Moderate" strength studies with Practitioners should generally follow a consistent findings, or evidence from a single "High" quality Moderate recommendation but remain alert to
study for recommending for or against the intervention. new information and be sensitive to patient A Moderate recommendation means that the benefits exceed
the potential harm (or that the potential harm clearly exceeds
the benefits in the case of a negative recommendation), but
the strength of the supporting evidence is not as strong.
Evidence from two or more "Low" strength studies with Practitioners should be cautious in deciding consistent findings, or evidence from a single Moderate whether to follow a recommendation classified quality study recommending for or against the intervention or as Limited, and should exercise judgment and
be alert to emerging publications that report evidence. Patient preference should have a A Limited recommendation means the quality of the
substantial influencing role. supporting evidence that exists is unconvincing, or that well-conducted studies show little clear advantage to one approach versus another. Evidence from a single low quality study or conflicting Practitioners should feel little constraint in findings that do not allow a recommendation for or against deciding whether to follow a recommendation the intervention. labeled as Inconclusive and should exercise
judgment and be alert to future publications that An Inconclusive recommendation means that there is a lack
clarify existing evidence for determining balance of compelling evidence resulting in an unclear balance of benefits versus potential harm. Patient between benefits and potential harm. preference should have a substantial influencing Consensus
The supporting evidence is lacking and requires the work Practitioners should be flexible in deciding group to make a recommendation based on expert opinion by whether to follow a recommendation classified considering the known potential harm and benefits associated as Consensus, although they may set boundaries
with the treatment. on alternatives. Patient preference should have a substantial influencing role. A Consensus recommendation means that expert opinion
supports the guideline recommendation even though there is
no available empirical evidence that meets the inclusion
criteria.
1 The AAOS will issue a consensus-based recommendation only when the service in question has virtually no associated harm and is of low cost (e.g. a history and physical) or when not establishing a recommendation could have catastrophic consequences. AAOS Clinical Practice Guidelines Unit Each recommendation was written using language that accounts for the final strength of the recommendation. This language, and the corresponding strength, is shown i Table 4 AAOS guideline language
Strength of
Guideline Language
We recommend
We suggest
We are unable to recommend for or against
In the absence of reliable evidence, it is the opinion of this work group*
* *Consensus based recommendations are made according to specific criteria. These criteria can be found in Appendix VI. CONSENSUS DEVELOPMENT
The recommendations and their strength were voted on using a structured voting
technique known as the nominal group technique.21 We present details of this technique
inVoting on guideline recommendations was conducted using a secret
ballot and work group members were blinded to the responses of other members. If
disagreement between work group members was significant, there was further discussion
to see whether the disagreement(s) could be resolved. Up to three rounds of voting were
held to attempt to resolve disagreements. If disagreements were not resolved following
three voting rounds, no recommendation was adopted. Lack of agreement is a reason that
the strength for some recommendations is labeled "Inconclusive."
STATISTICAL METHODS
When possible the results of statistical analysis conducted by the AAOS Clinical Practice
Guidelines Unit using STATA 10.0 (StataCorp LP, College Station, Texas) are reported.
The program was used to determine the magnitude of the treatment effect. For data
reported as means (and associated measures of dispersion) the mean difference between
groups was calculated. For proportions, the odds ratio was calculated as a measure of
treatment effect. When no events occur ("zero event") in a proportion, the variance of the
arcsine difference was used to determine statistical significance (p < 0.05).22
To compare recurrent and adjacent fracture rates we report the proportion of patients that experienced a fracture and percentage of patients that experienced a fracture. The variance of the arcsine difference was used to determine statistical significance (p < 0.05) of fracture rates.22 We performed meta-analyses using the random effects method of DerSimonian and Laird.23 Heterogeneity was assessed with the I-squared statistic.24 All meta-analyses were performed using STATA 10.0 (StataCorp LP, College Station, Texas) and the "metan" command. AAOS Clinical Practice Guidelines Unit To assess the power of an outcome to detect a statistically significant difference we determined whether the number of patients in the study was sufficient to detect a small, medium, or large effect, while assuming an alpha of 0.05 as the significance level, 80% power, and Cohen's definitions of small, medium, and large effects (a small effect is d = 0.2, a medium effect is d = 0.5, and a large effect is d = 0.8).25 When a study with a non-significant difference that was unable to detect a large effect it was categorized as low power. Studies able to detect medium effects or with statistically significant differences were categorized as high power. When published studies report measures of dispersion other than the standard deviation the value was estimated to facilitate calculation of the treatment effect. In studies that report standard errors or confidence intervals the standard deviation was back-calculated. In studies that only report the median, range, and size of the trial, we estimated the means and variances according to a published method.26 Studies that report results in graphical form were analyzed with TechDig 2.0 (Ronald B. Jones, Mundelein, Illinois) to estimate the mean and variance. In some circumstances statistical testing was conducted by the authors and measures of dispersion were not reported. In the absence of measures of dispersion, the results of the statistical analyses conducted by the authors are included in the analysis and are identified as those of the study authors. PEER REVIEW
The draft of the guideline and evidence report was peer reviewed by an external, outside
specialty panel that was nominated a priori by the physician work group prior to the
development of the guideline. The physician members of the AAOS Guidelines and
Technology Oversight Committee and the Evidence Based Practice Committee also
provided peer review of the draft document. Peer review was accomplished using a
structured peer review form (see. The draft guideline was sent to a total of
32 reviewers and 11 returned reviews (see The disposition of all non-
editorial peer review comments was documented and accompanied this guideline through
the public commentary and the AAOS guideline approval process.
PUBLIC COMMENTARY
After modifying the draft in response to peer review, the guideline was subjected to a
thirty day period of "Public Commentary." Commentators consist of members of the
AAOS Board of Directors (BOD), members of the Council on Research, Quality
Assessment, and Technology (CORQAT), members of the Board of Councilors (BOC),
and members of the Board of Specialty Societies (BOS). Based on these bodies, over 200
commentators had the opportunity to provide input into this guideline development
process. Of these, forty-nine members received the document for review and one member
returned public comments (see.
THE AAOS GUIDELINE APPROVAL PROCESS
Following public commentary, the draft was again modified by the AAOS Clinical
Practice Guidelines Unit and work group members. This final guideline draft was
approved by the AAOS Guidelines Oversight Committee, the AAOS Evidence Based
AAOS Clinical Practice Guidelines Unit Practice Committee, the AAOS Council on Research, Quality Assessment, and Technology, and the AAOS Board of Directors. Descriptions of these bodies are provided in REVISION PLANS
This guideline represents a cross-sectional view of current treatment and/or diagnosis and
may become outdated as new evidence becomes available. This guideline will be revised
in accordance with new evidence, changing practice, rapidly emerging treatment options,
new technology. This guideline will be updated or withdrawn in five years in accordance
with the standards of the National Guideline Clearinghouse.
GUIDELINE DISSEMINATION PLANS
The primary purpose of the present document is to provide interested readers with full
documentation about not only our recommendations, but also about how we arrived at
those recommendations. This document is also posted on the AAOS website at

Shorter versions of the guideline are available in other venues. Publication of most guidelines is announced by an Academy press release, articles authored by the work group and published in the Journal of the American Academy of Orthopaedic Surgeons, and articles published in AAOS Now. Most guidelines are also distributed at the AAOS Annual Meeting in various venues such as on Academy Row and at Committee Scientific Exhibits. Selected guidelines are disseminated by webinar, an Online Module for the Orthopaedic Knowledge Online website, Radio Media Tours, Media Briefings, and by distributing them at relevant Continuing Medical Education (CME) courses and at the AAOS Resource Center. Other dissemination efforts outside of the AAOS will include submitting the guideline to the National Guideline Clearinghouse and distributing the guideline at other medical specialty societies' meetings. AAOS Clinical Practice Guidelines Unit III. RECOMMENDATIONS AND SUPPORTING DATA
RECOMMENDATION 1
We suggest patients who present with an osteoporotic spinal compression fracture on
imaging with correlating clinical signs and symptoms suggesting an acute injury (0-5
days after identifiable event or onset of symptoms) and who are neurologically intact be
treated with calcitonin for 4 weeks.
Quality of
Quantity of
Critical
Evidence
Evidence
Downgrade
Outcome(s)
Strength of Recommendation: Moderate
Description: Evidence from two or more "Moderate" strength studies with consistent
findings, or evidence from a single "High" quality study for recommending for or against
the intervention. A Moderate recommendation means that the benefits exceed the
potential harm (or that the potential harm clearly exceeds the benefits in the case of a
negative recommendation), but the strength of the supporting evidence is not as strong.
Implications: Practitioners should generally follow a Moderate recommendation but
remain alert to new information and be sensitive to patient preferences.
Rationale
This recommendation is based on two Level II studies which showed benefit in reducing pain at 4 weeks using salmon calcitonin administered within 5 days of a fracture event.27, 28 In one study, 100 patients were treated with 200 IU nasal calcitonin or placebo. Calcitonin reduced pain in 4 positions (bedrest, sitting, standing, and walking) and the number of bedridden patients at 1, 2, 3, and 4 weeks in a clinically important manner. In a second study with 36 patients, similar results were found with calcitonin suppositories 200 IU. Side effects of calcitonin include mild dizziness.28 Two additional Level II studies with calcitonin showed benefit at longer periods of time (3-12) months but were not as well designed.29, 30 In one, possibly clinically important benefit was shown in pain reduction using nasal calcitonin in a two-month on and two month off fashion for 12 months compared to calcium 500 mg with vitamin D 200 IU.29 In another study, 200 IU nasal calcitonin led to possibly clinically important improvement in pain at 3 months when compared to 1000 mg calcium.30 The effect of subcutaneous administration of calcitonin is undetermined in a rigorous scientific manner. AAOS Clinical Practice Guidelines Unit Supporting Evidence
Two studies with moderately reliable data enrolling a total of 136 patients compared calcitonin against placebo among patients with an acute injury (0-5 days after injury).27, 28 In each study, only paracetamol was permitted as a rescue analgesic. Calcitonin reduced pain more than placebo at clinically important or possibly clinically important levels in both studies from 1-4 weeks (results presented i- Two additional studies with moderately reliable data enrolling a total of 82 patients compared calcitonin to non-placebo control.29, 30 As opposed to the two calcitonin vs. placebo studies, the time since injury was greater than 3 months in one study30 and not specified in the other.29 In each study, the calcitonin group also received calcium. The control group was calcium in the first study and calcium and vitamin D in the second study. A possibly clinically important improvement in pain occurred in the calcitonin group at 3 and 12 months, respectively, but there was no difference in function at 3 months AAOS Clinical Practice Guidelines Unit SUMMARY OF EVIDENCE
Table 5 Summary of Calcitonin Outcomes
2 weeks 3 weeks 4 weeks months
Mild enteric disturbances Oswestry Disability Pain bedridden - VAS Pain sitting - VAS Pain standing - VAS Pain walking - VAS Patients Bedridden circle-calcitonin compared to plac ebo; squar d to no calci tonin green-clinically important in favor of calcitonin; blue-possibly clinically important in favor of
Calcitonin; red-statistically significant in favor of placebo
grey-statistically significant; open-not statistically significant, X-underpowered study
Pain –VAS =Pain measured using the visual analog scale. Pain-NRS = Pain measured with the numerical rating scale. Please see Appendix XI for a list of all abbreviations used in this report. AAOS Clinical Practice Guidelines Unit STUDY QUALITY
Table 6 Quality of Included Studies for Recommendation 1 - Randomized Trials
× = Not Reported Duration
Treatments
Evidence
AAOS Clinical Practice Guidelines Unit Table 6 Quality of Included Studies for Recommendation 1 - Randomized Trials
× = Not Reported Duration
Treatments
Evidence
AAOS Clinical Practice Guidelines Unit
CALCITONIN VS. PLACEBO
Figure 1 Calcitonin vs. Placebo – Difference in Pain
Interpreting the Graphs Throughout the guideline we use line graphs to illustrate the differences in efficacy between the experimental and control groups of a study. Each point represents the difference between the two study groups for the designated outcome at that particular time point. A positive value indicates a better outcome (e.g., less pain) in the experimental group. The error bars represent the 95% Confidence Interval. The dotted line represents the Minimally Clinically Important Improvement (MCII) for the outcome. In the figure above, the difference in pain between the calcitonin and placebo groups is compared at 4 time points in two separate studies (Lyritis 1997 and Lyritis 1999). For instance, at 4 weeks the pain on VAS in the calcitonin group is about 7 units less than the pain in the placebo group in both studies. The difference is statistically significant because the confidence intervals do not cross 0, and the difference is clinically important because the lower confidence interval is greater than the MCII value. AAOS Clinical Practice Guidelines Unit Table 7 Calcitonin vs. Placebo - Pain
Difference
Clinically
Duration
between groups
Evidence
Important?
AAOS Clinical Practice Guidelines Unit Table 7 Calcitonin vs. Placebo - Pain
Difference
Clinically
Duration
between groups
Evidence
Important?
*95% Confidence Intervals estimated from medians and p-value (from Mann-Whitney test) Table 8 Calcitonin vs. Placebo – Bedridden Patients
Time After
Calcitonin
Duration
Evidence
Patients Bedridden Shaded cell indicates favored treatment Table 9 Calcitonin vs. Placebo – Adverse Events
Time After
Calcitonin
Duration
Evidence
Mild enteric disturbances Study lacked sufficient power to detect large effect for mild enteric disturbances; shaded cell indicates favored treatment AAOS Clinical Practice Guidelines Unit CALCITONIN VS. NO CALCITONIN
Table 10 Calcitonin vs. No Calcitonin – Pain and Function
Difference
Clinically
Time After
Important?
Duration
Evidence
groups (95%
3.2 (-7.1, 13.5) Papadokostakis study lacked sufficient power to detect large effect for Oswestry Disability; *Estimated from median and range; ○ = no statistically significant difference AAOS Clinical Practice Guidelines Unit RECOMMENDATION 2
Ibandronate and strontium ranelate are options to prevent additional symptomatic
fractures in patients who present with an osteoporotic spinal compression fracture on
imaging with correlating clinical signs and symptoms.
Quality of
Quantity of
Critical
Evidence
Evidence
Downgrade
Outcome(s)
Strength of Recommendation: Limited
Description: Evidence from two or more "Low" strength studies with consistent findings,
or evidence from a single "Moderate" quality study recommending for or against the
intervention or diagnostic. A Limited recommendation means the quality of the
supporting evidence that exists is unconvincing, or that well-conducted studies show little
clear advantage to one approach versus another.
Implications: Practitioners should exercise clinical judgment when following a
recommendation classified as Limited, and should be alert to emerging evidence that
might negate the current findings. Patient preference should have a substantial
influencing role.
Rationale
There have been numerous studies examining the effects of medical therapies for the treatment of osteoporosis to prevent radiographic fractures. The focus of this recommendation is not the use of medical therapies for treatment of osteoporosis (i.e. prevention of fragility fracture), but their use in patients with an existing fracture and the prevention of those patients experiencing symptomatic fractures (i.e. the critical outcome for this recommendation). Three studies of osteoporosis drugs exclusively enrolled symptomatic patients but none reported the critical outcome of a symptomatic fracture. Thirty-four additional studies were included that enrolled patients with symptomatic fractures or asymptomatic fractures (incident fracture determined by radiograph). Three of these studies reported the critical outcome of symptomatic fracture. One Level II study31 investigated daily (2.5 mg) and intermittent (20 mg every other day for 12 doses every 3 months) administration of ibandronate for symptomatic vertebral fractures compared to placebo. Daily and intermittent ibandronate treatment regimens reduced new symptomatic vertebral fractures in a statistically significant manner at 3 years. There were no statistically significant differences in adverse events between ibandronate and placebo groups including those in the upper gastrointestinal tract. One Level II study32investigated daily strontium ranelate (2g) for vertebral fractures compared to placebo. Strontium ranelate reduced new symptomatic vertebral fractures in a statistically significant manner at 1 and 3 years. The occurrence of adverse events was AAOS Clinical Practice Guidelines Unit similar between patients assigned to placebo or strontium ranelate. The only statistically significant differences were diarrhea, which occurred more frequently in patients receiving strontium ranelate, and incidence of gastritis, which occurred more frequently in patients receiving placebo. Effective as of July 15, 2010, Strontium Ranelate is not approved for marketing or the treatment of any medical condition in the United States. The United States Food and Drug Administration's (FDA) current policy regarding disclosure of marketing applications can be found in "Current Disclosure Policies for Marketing Applications" on the FDA website. One Level II study33investigated daily oral pamidronate (150 mg) for vertebral fractures compared to placebo. Oral pamidronate did not reduce new symptomatic vertebral fractures in a statistically significant manner at 3 years and adverse events were similar between patients receiving placebo or oral pamidronate. No recommendation is made for or against the use of any of the treatments considered not applicable to the reduction of future symptomatic vertebral fractures despite the large body of evidence for their use in osteoporosis. Supporting Evidence
We have tabled data on radiographic and symptomatic fracture from 37 studies, analyzing 18,305 unique patients, with reliable or moderately reliable data that report the cumulative number of patients with an incident or recurrent fracture within the first 3 months up to 4.5 years following initiation of treatment. Three of the 35 studies enrolled patients who had symptoms of osteoporotic spinal compression fracture. None of these studies report recurrent or adjacent fractures as symptomatic. However, three different included studies (i.e. studies that enrolled symptomatic and asymptomatic patients) did report recurrent or adjacent fractures as symptomatic. Twenty nine of the 37 studies enroll an exclusively female population.illustrates the symptomatic fractures and the radiographic fractures reported as outcomes in the included studies which compared the treatment to a placebo or control.lists the comparisons from the included studies for this recommendation including direct comparisons of treatments (i.e. not placebo or control). AAOS Clinical Practice Guidelines Unit
SUMMARY OF EVIDENCE
Table 11 Fracture Prevention Outcomes
months months
years months years
Calcitonin (100IU) Calcitonin (200IU) Calcitonin (300IU) Estrogen+Fluoride Etidronate+Estrogen Etidronate+Phosphate Ibandronate (intermittent) Ibandronate (daily) Raloxifene (60 & 120mg) Risedronate (2.5mg) Risedronate (5mg) Strontium Ranelate (2g) Strontium Ranelate (1g) Strontium Ranelate (0.5g) Teriparatide (20 & 40μg) Vertebroplasty ○x♦ ○ circle-compared to placebo; squar e-compar eatment; dia mond-rep orted as " fracture"; green-symptomatic fracture; grey-radiographic fracture; closed-statistically significant; open-not
statistically significant, X-underpowered study; red-statistically significant in favor of
placebo/conservative; not all treatments were investigated at different dosages; g-grams; mg-milligrams;
mcg-micrograms IU-international unit
AAOS Clinical Practice Guidelines Unit Table 12 Treatment Comparisons for Recommendation 2
Compared to Placebo or Control
Calcitonin 29, 35 Etidronate 38, 39 Etidronate+Estrogen 38 Etidronate+Phosphate 39 Fluoride 36, 40-43 Ibandronate 31† Menatetrenone 45 Pamidronate 33† Raloxifene 47, 48 Risedronate 49-51 Strontium Ranelate 32, 52† Vertebroplasty 1* 55 Direct Comparisons
Alendronate to Alfacalcidol 56 Estrogen to Estrogen+Calcitriol 57 Etidronate to Fluoride 58 Etidronate to Risedronate 59 Etidronate to Phosphate to Etidronate+Phosphate 39 Kyphoplasty to Vertebroplasty 60, 61 Underpowered Comparisons Alendronate to Etidronate 62* Calcitriol to Placebo63 Estrogen+Fluoride to Control 36 Estrogen to Etidronate to Etidronate+Estrogen 38 Estrogen to Fluoride to Estrogen+Fluoride 36 Nandrolone to 1α-OH D3 to Calcium infusion 64 Teriparatide to Teriparatide+Calcitonin 65 * study enrolls symptomatic patients; † study reports symptomatic recurrent or adjacent spinal compression fracture AAOS Clinical Practice Guidelines Unit STUDY QUALITY
Table 13 Quality of Included Studies for Recommendation 2 - Randomized Trials
× = Not Reported Duration
Treatments
Evidence
Vertebroplasty vs. Vertebroplasty vs. Vertebroplasty vs. Vertebroplasty vs. Menatetrenone vs. Minondronate vs. AAOS Clinical Practice Guidelines Unit Table 13 Quality of Included Studies for Recommendation 2 - Randomized Trials
× = Not Reported Duration
Treatments
Evidence
Strontium Ranelate Strontium Ranelate Strontium Ranelate Strontium Ranelate Estrogen+Calcitriol AAOS Clinical Practice Guidelines Unit Table 13 Quality of Included Studies for Recommendation 2 - Randomized Trials
× = Not Reported Duration
Treatments
Evidence
Estrogen+Fluoride Strontium Ranelate Teriparatide vs. AAOS Clinical Practice Guidelines Unit Table 13 Quality of Included Studies for Recommendation 2 - Randomized Trials
× = Not Reported Duration
Treatments
Evidence
Etidronate+Estrogen Teriparatide vs. Teriparatide and AAOS Clinical Practice Guidelines Unit Table 13 Quality of Included Studies for Recommendation 2 - Randomized Trials
× = Not Reported Duration
Treatments
Evidence
Etidronate vs. Phosphate vs. Etidronate+Phosphate Calcium infusion AAOS Clinical Practice Guidelines Unit Table 14 Quality of Included Studies for Recommendation 2 - Prospective Comparative Studies
× = Not Reported Duration N
Treatments
Evidence
Vertebroplasty vs. Adjacent Fracture AAOS Clinical Practice Guidelines Unit ALENDRONATE
One study with reliable data compared alendronate to placebo and reported the cumulative number of patients with an incident or recurring fracture within three years. 34 Table 15 Alendronate vs. Placebo - Fractures
Alendronate
Duration
shaded box indicates favored treatment ALENDRONATE VS. ALFACALCIDOL
One study with moderately reliable data, which enrolled men and women, compared alendronate to alfacalcidol and reported the cumulative number of patients with an incident or recurring fracture within two years. 56 Table 16 Alendronate vs. Alfacalcidol - Fractures
Alendronate
Duration
Study enrolled males and females ALENDRONATE VS. ETIDRONATE
One study with moderately reliable data, which enrolled patients with symptoms of spinal compression fractures, compared alendronate to etidronate and reported the cumulative number of patients with an incident or recurring fracture within six months. 62 Table 17 Alendronate vs. Etidronate - Fractures
Alendronate
Etidronate
Duration
Patients were symptomatic at enrollment AAOS Clinical Practice Guidelines Unit CALCITONIN
Two studies with moderately reliable data compared salmon calcitonin to placebo and reported the cumulative number of patients with an incident or recurring fracture within one or three years. 29, 35 In both studies the 200 IU dosage resulted in statistically significant differences in cumulative fracture rates. Table 18 Calcitonin vs. Placebo - Fractures
Calcitonin
Duration
p-value Power
shaded box indicates favored treatment CALCITRIOL
One study with reliable data compared calcitriol to placebo and reported the cumulative number of patients with an incident or recurring fracture within two years. 63 Table 19 Calcitriol vs. Placebo - Fractures
Calcitriol
Duration
AAOS Clinical Practice Guidelines Unit ESTROGEN
Three studies with moderately reliable data compared estrogen to a placebo or control group and reported the cumulative number of patients with an incident or recurring fracture within one year, twenty seven months, or four years. 36-38 We conducted a meta-analysis (using the arcsin difference 22) of these three studies in an effort to improve the power of this analysis.illustrates a non-significant effect with substantial heterogeneity (I2 = 60.7%). Table 20 Estrogen vs. Placebo or Control - Fractures
Estrogen
Duration
AAOS Clinical Practice Guidelines Unit Figure 2 Meta-analysis of Estrogen vs. Placebo or Control - Fractures
Overall (I-squared = 60.7%, p = 0.078) . Favors Placebo/Control Favors Estrogen AAOS Clinical Practice Guidelines Unit ESTROGEN VS. ESTROGEN+CALCITRIOL
One study with moderately reliable data compared the combination of estrogen and calcitriol to estrogen alone and reported the cumulative number of patients with an incident or recurring fracture within two years. 57 Table 21 Estrogen vs. Estrogen+Calcitriol - Fractures
Estrogen
Outcome Duration
One study with moderately reliable data compared the combination of estrogen and etidronate to a control group and reported the cumulative number of patients with an incident or recurring fracture within four years. 38 Table 22 Estrogen+Etidronate vs. Control - Fractures
Duration
shaded box indicates favored treatment ESTROGEN VS. ETIDRONATE VS. ESTROGEN+ ETIDRONATE
One study with moderately reliable data compared estrogen to etidronate to estrogen +etidronate and reported the cumulative number of patients with an incident or recurring fracture within four years. 38 Table 23 Estrogen vs. Etidronate vs. Etidronate+Estrogen - Fractures
Estrogen
Etidronate
Outcome Duration
p-value Power
Estrogen
p-value Power
AAOS Clinical Practice Guidelines Unit Estrogen
Etidronate
Outcome Duration
p-value Power
Etidronate Estrogen+Etidronate
p-value Power
AAOS Clinical Practice Guidelines Unit One study with moderately reliable data compared the combination of estrogen and fluoride to a control group and reported the cumulative number of patients with an incident or recurring fracture within twenty seven months. 36 Table 24 Estrogen+Fluoride vs. Placebo - Fractures
Duration
ESTROGEN VS. FLUORIDE VS. ESTROGEN+FLUORIDE
One study with moderately reliable data compared estrogen to fluoride to estrogen+fluoride and reported the cumulative number of patients with an incident or recurring fracture within twenty seven months. 36 Table 25 Estrogen vs. Fluoride vs. Estrogen+Fluoride - Fractures
Estrogen
Fluoride
Duration
Estrogen
Fluoride
AAOS Clinical Practice Guidelines Unit ETIDRONATE
Two studies with moderately reliable data compared etidronate to a placebo or control group and reported the cumulative number of patients with an incident or recurring fracture within two years or four years. 38, 39 Table 26 Etidronate vs. Placebo or Control - Fractures
Etidronate
Duration
ETIDRONATE VS. ALENDRONATE
One study with moderately reliable data, which enrolled patients with symptoms of spinal compression fractures, compared etidronate to alendronate and reported the cumulative number of patients with an incident or recurring fracture within six months. 62 Table 27 Etidronate vs. Alendronate - Fractures
Etidronate
Alendronate
Duration
Patients were symptomatic at enrollment ETIDRONATE VS. RISEDRONATE
One study with moderately reliable data compared etidronate to risedronate and reported the cumulative number of patients with an incident or recurring fracture within four years. 59 Table 28 Etidronate vs. Risedronate - Fractures
Etidronate
Risedronate
Duration
AAOS Clinical Practice Guidelines Unit Percentages reported by study authors, authors do not report sufficient information for n/N ETIDRONATE VS. FLUORIDE
One study with moderately reliable data compared etidronate to fluoride and reported the cumulative number of patients with an incident or recurring fracture within three years. 58 Table 29 Etidronate vs. Fluoride - Fractures
Etidronate
Fluoride
Duration
One study with moderately reliable data compared the combination of etidronate and estrogen to a control group and reported the cumulative number of patients with an incident or recurring fracture within four years. 38 Table 30 Etidronate+Estrogen vs. Control - Fractures
Duration
shaded box indicates favored treatment ETIDRONATE VS. ESTROGEN VS. ETIDRONATE+ESTROGEN
One study with moderately reliable data compared etidronate to estrogen to etidronate+estrogen and reported the cumulative number of patients with an incident or recurring fracture within four years. 38 Table 31 Etidronate vs. Estrogen vs. Etidronate+Estrogen - Fractures
Etidronate
Estrogen
Outcome Duration
p-value Power
Etidronate Estrogen+Etidronate
p-value Power
AAOS Clinical Practice Guidelines Unit Etidronate
Estrogen
Outcome Duration
p-value Power
Estrogen
p-value Power
AAOS Clinical Practice Guidelines Unit One study with moderately reliable data compared the combination of etidronate and phosphate to a placebo group and reported the cumulative number of patients with an incident or recurring fracture within two years. 39 Table 32 Etidronate+Phosphate vs. Placebo - Fractures
Duration
shaded box indicates favored treatment ETIDRONATE VS. PHOSPHATE VS. ETIDRONATE+PHOSPHATE
One study with moderately reliable data compared etidronate to phosphate to etidronate+phosphate and reported the cumulative number of patients with an incident or recurring fracture within two years. 39 Table 33 Etidronate vs. Phosphate vs. Etidronate+Phosphate - Fractures
Etidronate
Phosphate
Outcome Duration
Etidronate
Phosphate
AAOS Clinical Practice Guidelines Unit AAOS Clinical Practice Guidelines Unit FLUORIDE
Five studies with moderately reliable data compared fluoride to a placebo or control group and reported the cumulative number of patients with an incident or recurring fracture within twenty seven months, three years or four and a half years. 36, 40-43 We conducted a meta-analysis (using the arcsin difference 22) of these five studies in an effort to address the differences in the direction of the effect in different trials.illustrates a non-significant effect with substantial heterogeneity (I2 = 87.2%). Table 34 Fluoride vs. Placebo or Control - Fractures
Fluoride
Duration
shaded box indicates favored treatment AAOS Clinical Practice Guidelines Unit Figure 3 Meta-analysis of Fluoride vs. Placebo or Control - Fractures
Overall (I-squared = 87.2%, p = 0.000) . Favors Placebo/Control Favors Fluoride AAOS Clinical Practice Guidelines Unit FLUORIDE VS. ETIDRONATE
One study with moderately reliable data compared fluoride to etidronate and reported the cumulative number of patients with an incident or recurring fracture within three years. 58 Table 35 Fluoride vs. Etidronate - Fractures
Fluoride
Etidronate
Duration
One study with moderately reliable data compared the combination of fluoride and estrogen to a placebo and reported the cumulative number of patients with an incident or recurring fracture within twenty seven months. 36 Table 36 Fluoride+Estrogen vs. Placebo - Fractures
Duration
FLUORIDE VS. ESTROGEN VS. FLUORIDE+ESTROGEN
One study with moderately reliable data compared fluoride to estrogen to estrogen+fluoride and reported the cumulative number of patients with an incident or recurring fracture within twenty seven months. 36 Table 37 Fluoride vs. Estrogen vs. Fluoride+Estrogen - Fractures
Fluoride
Estrogen
Duration
Fluoride
AAOS Clinical Practice Guidelines Unit Fluoride
Estrogen
Duration
Estrogen
AAOS Clinical Practice Guidelines Unit IBANDRONATE
One study with moderately reliable data compared ibandronate intermittent or daily to placebo and reported the cumulative number of patients with an incident or recurring fracture within three years. 31 Additionally, this study reports the proportion of fractures that were symptomatic. Table 38 Ibandronate vs. Placebo - Fractures
Ibandronate
Duration
Ibandronate
Duration
shaded box indicates favored treatment IPRIFLAVONE
One study with moderately reliable data compared ipriflavone to placebo and reported the cumulative number of patients with an incident or recurring fracture within two years. 44 Table 39 Ipriflavone vs. Placebo - Fractures
Ipriflavone
Duration
shaded box indicates favored treatment AAOS Clinical Practice Guidelines Unit One study with moderately reliable data compared menatetrenone to a control group and reported the cumulative number of patients with an incident or recurring fracture within three years. 45 Table 40 Menatetrenone vs. Control - Fractures
Duration
One study with reliable data compared minondronate to placebo and reported the cumulative number of patients with an incident or recurring fracture within two years. Table 41 Minondronate vs. Placebo - Fractures
Duration
shaded box indicates favored treatment NANDROLONE VS. 1Α-OH D3 VS. CALCIUM INFUSION
One study with moderately reliable data, which enrolled men and women, compared nandrolone to 1α-hydroxyvitaman D3 to
calcium infusion and reported the cumulative number of patients with an incident or recurring fracture within two years. 64
Table 42 Nandrolone vs. 1α-hydroxyvitaman D3 vs. Calcium Infusion - Fractures
Nandrolone
1α-OH D3
Duration
Study enrolled males and females Nandrolone
Infusion
AAOS Clinical Practice Guidelines Unit Nandrolone
1α-OH D3
Duration
1α-OH D3
Infusion p-value
AAOS Clinical Practice Guidelines Unit PAMIDRONATE
One study with moderately reliable data, which enrolled men and women, compared pamidronate to placebo and reported the cumulative number of patients with an incident or recurring fracture within three years. 33 Additionally, this study reports the proportion of fractures that were symptomatic. Table 43 Pamidronate vs. Placebo - Fractures
Pamidronate
Duration
Study enrolled males and females, shaded box indicates favored treatment PHOSPHATE
One study with moderately reliable data compared phosphate to placebo and reported the cumulative number of patients with an incident or recurring fracture within two years. 39 Table 44 Phosphate vs. Placebo - Fractures
Phosphate
Duration
PHOSPHATE VS. ETIDRONATE VS. PHOSPHATE+ETIDRONATE
One study with moderately reliable data compared phosphate to etidronate to etidronate+phosphate and reported the cumulative number of patients with an incident or recurring fracture within two years. 39 Table 45 Phosphate vs. Etdironate vs. Phosphate+Etidronate - Fractures
Phosphate
Etidronate
Outcome Duration
p-value Power
AAOS Clinical Practice Guidelines Unit Phosphate
Etidronate
Outcome Duration
p-value Power
Phosphate
p-value Power
Etidronate
p-value Power
AAOS Clinical Practice Guidelines Unit RALOXIFENE
Two studies with moderately reliable data compared raloxifene to placebo and reported the cumulative number of patients with an incident or recurring fracture within one or three years. 47, 48 Table 46 Raloxifene vs. Placebo - Fractures
Raloxifene
Duration
Lufkin 1998: baseline differences in age, shaded box indicates favored treatment RISEDRONATE
Three studies with moderately reliable data compared risedronate to placebo and reported the cumulative number of patients with an incident or recurring fracture within two or three years. 49-51 Table 47 Risedronate vs. Placebo - Fractures
Risedronate
Duration
shaded box indicates favored treatment AAOS Clinical Practice Guidelines Unit RISEDRONATE VS. ETIDRONATE
One study with moderately reliable data compared risedronate to etidronate and reported the cumulative number of patients with an incident or recurring fracture within four years. 59 Table 48 Risedronate vs. Etidronate - Fractures
Risedronate
Etidronate
Duration
Percentages reported by study authors, do not report sufficient information for n/N AAOS Clinical Practice Guidelines Unit STRONTIUM RANELATE
Two studies with moderately reliable data compared strontium ranelate to placebo and reported the cumulative number of patients with an incident or recurring fracture within one, two, or three years. 32, 52 Additionally, one study reports the proportion of fractures that were symptomatic. 70 Table 49 Strontium Ranelate vs. Placebo - Fractures
Strontium
Ranelate
Dosage Duration
shaded box indicates favored treatment AAOS Clinical Practice Guidelines Unit One study with moderately reliable data compared teriparatide to placebo and reported the cumulative number of patients with an incident or recurring fracture within two years. 53 Table 50 Teriparatide vs. Placebo - Fractures
Duration
shaded box indicates favored treatment TERIPARATIDE VS. TERIPARATIDE+CALCITONIN
One study with moderately reliable data compared teriparatide to teriparatide with calcitonin and reported the cumulative number of patients with an incident or recurring fracture within two years. 65 Table 51 Teriparatide vs. Teriparatide+Calcitonin - Fractures
Duration
AAOS Clinical Practice Guidelines Unit KYPHOPLASTY
One study with moderately reliable data, which enrolled men and women with symptoms of spinal compression fractures, compared kyphoplasty to conservative treatment and reported the cumulative number of patients with an incident or recurring fracture within one year. 54 Table 52 Kyphoplasty vs. Conservative Treatment - Fractures
Kyphoplasty
Duration
Study enrolled males and females, patients were symptomatic at enrollment VERTEBROPLASTY VS. PLACEBO
One study with reliable data, which enrolled men and women with symptoms of spinal compression fractures, compared vertebroplasty to placebo and reported the cumulative number of patients with an incident or recurring fracture within three and six months. 1 Table 53 Vertebroplasty vs. Placebo - Fractures
Duration
Study enrolled males and females, patients were symptomatic at enrollment VERTEBROPLASTY VS. CONSERVATIVE
One study with moderately reliable data compared vertebroplasty to conservative treatment and reported the cumulative number of patients with an incident or recurring fracture within the first three months.55 Additionally, this study reports the number of these fractures that occurred on adjacent vertebrae. Table 54 Vertebroplasty vs. Conservative - Fractures
Vertebroplasty Conservative
Duration
AAOS Clinical Practice Guidelines Unit Vertebroplasty Conservative
Duration
AAOS Clinical Practice Guidelines Unit KYPHOPLASTY VS. VERTEBROPLASTY
One study with reliable data, which enrolled men and women, compared kyphoplasty to vertebroplasty and reported the cumulative number of patients with an incident or recurring fracture within six months. 61 Another study with moderately reliable data compared kyphoplasty to vertebroplasty and reported the cumulative number of adjacent fractures within the first four months.60 Table 55 Kyphoplasty vs. Vertebroplasty - Fractures
Kyphoplasty
Duration
Study enrolled males and females, shaded box indicates favored treatment AAOS Clinical Practice Guidelines Unit RECOMMENDATION 3
We are unable to recommend for or against bed rest, complementary and alternative medicine, or opioids/analgesics for
patients who present with an osteoporotic spinal compression fracture on imaging with correlating clinical signs and symptoms
and who are neurologically intact.
Strength of Recommendation: Inconclusive
Description: Evidence from a single low quality study or conflicting findings that do not allow a recommendation for or
against the intervention. An Inconclusive recommendation means that there is a lack of compelling evidence resulting in an
unclear balance between benefits and potential harm.
Implications: Practitioners should feel little constraint in following a recommendation labeled as Inconclusive, exercise
clinical judgment, and be alert for emerging evidence that clarifies or helps to determine the balance between benefits and
potential harm. Patient preference should have a substantial influencing role.
Rationale
There are no existing adequate data to address the use of the following potential conservative, nonoperative therapies for a spinal compression fracture in patients who are neurologically intact: bed rest or complementary, alternative medicines and opioids/analgesics. AAOS Clinical Practice Guidelines Unit RECOMMENDATION 4
It is an option to treat patients who present with an osteoporotic spinal compression fracture at L3 or L4 on imaging with
correlating clinical signs and symptoms suggesting an acute injury and who are neurologically intact with an L2 nerve root
block.
Quality of
Quantity of
Critical
Evidence
Evidence
Downgrade
Outcome(s)
Strength of Recommendation: Limited
Description: Evidence from two or more "Low" strength studies with consistent findings, or evidence from a single
"Moderate" quality study recommending for or against the intervention or diagnostic. A Limited recommendation means the
quality of the supporting evidence that exists is unconvincing, or that well-conducted studies show little clear advantage to one
approach versus another.
Implications: Practitioners should exercise clinical judgment when following a recommendation classified as Limited, and
should be alert to emerging evidence that might negate the current findings. Patient preference should have a substantial
influencing role.
Rationale
The role of L2 selective nerve root blocks as a non-operative treatment for back pain associated with mid-lumbar compression fracture has been studied.66 In this trial, two groups of 30 acute fracture patients received unilateral L2 root block or subcutaneous injection as a control. A possibly clinically important benefit was seen with the treatment at two weeks but became nonsignificant at one month. The effect of bilateral L2 injection was not addressed in this study or the literature. Based on this single study, support for L2 root injection for treating new onset back pain associated with L3 or L4 compression fractures is weak and is therefore only an option for temporary pain relief. AAOS Clinical Practice Guidelines Unit Supporting Evidence
One study with moderately reliable data enrolling 60 patients compared nerve block to a control group of subcutaneous
injection.66 The study occurred with "acute" injury patients. All patients received nonsteroidal anti-inflammatory
drugs (NSAIDs) and soft lumbar support belts. Patients were allowed a maximum of 7 days of bed rest. Pain was
reduced more in the nerve block group for two weeks at possibly clinically significant levels. The effects were no longer
significant after two weeks, and there were no differences in function at any duration (
AAOS Clinical Practice Guidelines Unit Table 57 -
AAOS Clinical Practice Guidelines Unit STUDY QUALITY
Table 56 Quality of Included Study for Recommendation 4 - Randomized Trial
× = Not Reported Duration
Treatments
Evidence
AAOS Clinical Practice Guidelines Unit Table 56 Quality of Included Study for Recommendation 4 - Randomized Trial
× = Not Reported Duration
Treatments
Evidence
AAOS Clinical Practice Guidelines Unit NERVE BLOCK VS. SUBCUTANEOUS INJECTION
Figure 4 Nerve Block vs. Subcutaneous Injection - Difference in Pain
AAOS Clinical Practice Guidelines Unit Table 57 Nerve block vs. Subcutaneous Injection - Pain
Difference
Clinically
Duration
between groups
Evidence
Important?
1.0 (-0.01, 2.0) -0.2 (-1.2, 0.8) -0.4 (-1.6, 0.8) *Authors reported the difference at 2 weeks was statistically significant according to the Wilcoxon signed rank test (results presented in this table are based on an independent t-test) Table 58 Nerve block vs. Subcutaneous Injection – Physical Function
Difference
Clinically
Duration
between groups
Evidence
Important?
-0.5 (-2.8, 1.8) AAOS Clinical Practice Guidelines Unit Table 59 Nerve block vs. Control – SF-36
Time After
Difference between
Clinically
Duration
Evidence
groups (95% CI)
Important?
-0.5 (-7.2, 6.2) 4.6 (-1.7, 11.0) -0.2 (-3.9, 3.5) -0.6 (-7.3, 6.1) 5.0 (-1.9, 11.9) 4.0 (-2.5, 10.5) -4.5 (-8.8, -0.2) -1.0 (-6.2, 4.2) 27.2 (22.0, 32.4) -0.4 (-6.1, 5.3) -1.1 (-6.9, 4.7) -1.9 (-7.1, 3.3) -5.2 (-9.8, -0.6) -1.6 (-6.6, 3.4) *Authors report this as not significant; possibly a typo in the reported results AAOS Clinical Practice Guidelines Unit RECOMMENDATION 5
We are unable to recommend for or against treatment with a brace for patients who
present with an osteoporotic spinal compression fracture on imaging with correlating
clinical signs and symptoms and who are neurologically intact.
Quality of
Quantity of
Critical
Evidence
Evidence
Downgrade
Outcome(s)
Strength of Recommendation: Inconclusive
Description: Evidence from a single low quality study or conflicting findings that do not
allow a recommendation for or against the intervention. An Inconclusive
recommendation means that there is a lack of compelling evidence resulting in an unclear
balance between benefits and potential harm.
Implications: Practitioners should feel little constraint in following a recommendation
labeled as Inconclusive, exercise clinical judgment, and be alert for emerging evidence
that clarifies or helps to determine the balance between benefits and potential harm.
Patient preference should have a substantial influencing role.
Rationale
There was only one Level II article studying the effect of bracing.67 This recommendation was downgraded to inconclusive because neither the age nor the level of the fracture being treated was reported. Additionally, this study investigated only a single specific type of brace for all fractures which call into question the generalizability of these results to all braces. While the results were statistically significant, we do not know if they were clinically important (MCII unknown). Based on this single study, there is insufficient evidence to recommend for or against the use of bracing. Supporting Evidence
One study with moderately reliable data enrolling 62 patients investigated brace vs. no brace among patients whose time after injury was not specified.67 Patients wore the back orthosis for 6 months. Pain, function, and well-being measures favored the brace group at 6 months AAOS Clinical Practice Guidelines Unit STUDY QUALITY
Table 60 Quality of Included Study for Recommendation 5 - Randomized Trial
× = Not Reported Duration
Treatments
Evidence
Brace vs. control Brace vs. control Brace vs. control Brace vs. control AAOS Clinical Practice Guidelines Unit BRACE VS. NO BRACE
Table 61 Brace vs. No Brace – Pain and Limitations of Daily Living
Difference
Clinically
Duration
between groups
Evidence
Important?
(95% CI)*
Pain – Miltner's rating scale Limitations of daily living – Limitations of daily living – 12.7 (9.7, 15.7) *Difference in change scores AAOS Clinical Practice Guidelines Unit RECOMMENDATION 6
We are unable to recommend for or against a supervised or unsupervised exercise
program for patients who present with an osteoporotic spinal compression fracture on
imaging with correlating clinical signs and symptoms and who are neurologically intact.
Quality of
Quantity of
Critical
Evidence
Evidence
Downgrade
Outcome(s)
Strength of Recommendation: Inconclusive
Description: Evidence from a single low quality study or conflicting findings that do not
allow a recommendation for or against the intervention. An Inconclusive
recommendation means that there is a lack of compelling evidence resulting in an unclear
balance between benefits and potential harm.
Implications: Practitioners should feel little constraint in following a recommendation
labeled as Inconclusive, exercise clinical judgment, and be alert for emerging evidence
that clarifies or helps to determine the balance between benefits and potential harm.
Patient preference should have a substantial influencing role.
Rationale
A single Level II study evaluated fractures with low back pain of greater than 3 months' duration using a home-based exercise program compared to a control group continuing usual activities using the Osteoporosis Quality of Life Questionnaire, which evaluates 5 domains.68 We downgraded this recommendation to inconclusive because the low back pain experienced by patients in this study may not be the direct result of a specific spinal compression fracture. Results did favor exercise to improve the symptom domain at 6 and 12 months and the emotion domain at 6 months but not at 12 months. There was no difference in the physical function domain at 6 or 12 months. When evaluating the domain of activities of daily living there was no difference at 6 months but there was evidence favoring exercise at 12 months. In evaluating the leisure/social domain there was evidence to support exercise at the 6 month level but no difference at the 12 month level. The clinical importance of these outcomes is unknown. There was no documentation that the back pain measured was a direct result of the fracture. Supporting Evidence
One study with moderately reliable data enrolling 60 patients compared a home-based exercise program vs. a control group continuing usual activities.68 The patients had a chronic injury (>3 months since fracture). Several domains of the Osteoporosis Quality of Life Questionnaire favored the exercise group at either 6 or 12 months, but the Sickness Impact Profile showed no significant difference - AAOS Clinical Practice Guidelines Unit STUDY QUALITY
Table 62 Quality of Included Study for Recommendation 6 - Randomized Trial
× = Not Reported Duration
Treatments
Evidence
AAOS Clinical Practice Guidelines Unit EXERCISE VS. NO EXERCISE
Table 63 Exercise vs. Control - Osteoporosis Quality of Life Questionnaire (OQLQ)
Difference
Clinically
Duration
between groups
Evidence
Important?
0.44 (0.16, 0.73) 12 months 0.38 (-0.05, 0.81) 0.34 (0.02, 0.66) 12 months 0.30 (-0.21, 0.81) 0.22 (-0.08, 0.52) 12 months 0.16 (-0.35, 0.68) 0.17 (-0.09, 0.43) 12 months 0.34 (-0.11, 0.79) 0.39 (-0.02, 0.81) 12 months 0.26 (-0.22, 0.74) *Baseline-adjusted p-values Table 64 Exercise vs. Control - Sickness Impact Profile (SIP)
Difference
Clinically
Duration between groups Favors*
Evidence
Important?
SIP Physical Domain 0.80 (-1.52, 3.13 SIP Psychosocial Domain 6 months 0.09 (-3.21, 3.41) 0.55 (-1.81, 2.91) *Baseline-adjusted p-values AAOS Clinical Practice Guidelines Unit RECOMMENDATION 7
We are unable to recommend for or against electrical stimulation for patients who present with an osteoporotic spinal
compression fracture on imaging with correlating clinical signs and symptoms and who are neurologically intact.
Quality of
Quantity of
Critical
Evidence
Evidence
Downgrade
Outcome(s)
Strength of Recommendation: Inconclusive
Description: Evidence from a single low quality study or conflicting findings that do not allow a recommendation for or
against the intervention. An Inconclusive recommendation means that there is a lack of compelling evidence resulting in an
unclear balance between benefits and potential harm.
Implications: Practitioners should feel little constraint in following a recommendation labeled as Inconclusive, exercise
clinical judgment, and be alert for emerging evidence that clarifies or helps to determine the balance between benefits and
potential harm. Patient preference should have a substantial influencing role.
Rationale
One Level I study addressed the use of electrical stimulation limited to symptomatic patients with chronic vertebral compression fractures, with short term follow up of three months.69 This study had insufficient power to find a difference in this treatment when compared to a control group for the critical outcome measure of pain relief as well as quality of life. A surrogate outcome measure of change in use of NSAIDs was reported but the change in use was based on percentage of patients using less NSAIDs with electrical stimulation as opposed to the actual amount of NSAIDs used by individual patients. This outcome measure has little clinical significance and no quantitative measure to gauge pre vs. post treatment effect. Because of the inability to detect a difference in pain (an outcome that is critical to understand treatment effectiveness) or quality of life ,the evidence is inconclusive and we are unable to recommend for or against this treatment. AAOS Clinical Practice Guidelines Unit Supporting Evidence
One study with reliable data from 41 patients compared CCEF stimulation vs. placebo stimulation.69 Patients had had
a fracture for greater than 6 months, and all patients began the study taking analgesic medication. The study lacked
power to detect a significant difference in pain or quality of life between the two groups. At 10 and 11 weeks only, the
active treatment group had significantly fewer patients continuing NSAID usage-
AAOS Clinical Practice Guidelines Unit AAOS Clinical Practice Guidelines Unit STUDY QUALITY
Table 65 Quality of Included Study for Recommendation 7 - Randomized Trial
× = Not Reported Duration
Treatments
Evidence
CCEF stimulation vs. placebo CCEF stimulation vs. placebo CCEF stimulation vs. placebo CCEF stimulation vs. placebo CCEF stimulation vs. placebo CCEF stimulation vs. placebo CCEF stimulation vs. placebo CCEF stimulation vs. placebo AAOS Clinical Practice Guidelines Unit Table 65 Quality of Included Study for Recommendation 7 - Randomized Trial
× = Not Reported Duration
Treatments
Evidence
CCEF stimulation vs. placebo CCEF stimulation vs. placebo CCEF stimulation vs. placebo CCEF stimulation vs. placebo CCEF stimulation vs. placebo CCEF stimulation vs. placebo CCEF stimulation vs. placebo CCEF stimulation vs. placebo CCEF stimulation vs. placebo AAOS Clinical Practice Guidelines Unit Table 65 Quality of Included Study for Recommendation 7 - Randomized Trial
× = Not Reported Duration
Treatments
Evidence
CCEF stimulation vs. placebo CCEF stimulation vs. placebo CCEF stimulation vs. placebo AAOS Clinical Practice Guidelines Unit ELECTRICAL STIMULATION VS. PLACEBO
Figure 5 CCEF Stimulation vs. Placebo - Difference in Pain
AAOS Clinical Practice Guidelines Unit Table 66 CCEF Stimulation vs. Placebo - Pain
Difference
Clinically
Duration
between groups
Evidence
Important?
-0.7 (-4.2, 2.8) -0.7 (-4.2, 2.8) -1.5 (-5.0, 2.0) Study lacked sufficient power to detect large effect Table 67 CCEF Stimulation vs. Placebo - Quality of Life
Difference
Clinically
Duration
between groups
Evidence
Important?
-1.8 (-11.0, 7.4) -6.4 (-15.6, 2.8) -4.8 (-14.0, 4.4) -4.2 (-13.4, 5.0) *Quality of life questionnaire of the European Foundation for Osteoporosis; study lacked sufficient power to detect large effect AAOS Clinical Practice Guidelines Unit Table 68 CCEF Stimulation vs. Placebo - Patients continuing NSAID usage
Time After
Duration
Evidence
0.32 (0.07, 1.38) 0.30 (0.06, 1.35) 0.67 (0.13, 3.15) 0.28 (0.02, 1.91) 0.56 (0.08, 3.52) 0.22 (0.004, 2.64) 0.36 (0.03, 2.61) 0.44 (0.06, 2.56) 0.13 (0.003, 1.32) 0.07 (0.002, 0.65) 0.09 (0.002, 0.81) 0.18 (0.02, 1.16) Study lacked sufficient power to detect large effect for each non-significant outcome; shaded cell indicates favored treatment AAOS Clinical Practice Guidelines Unit RECOMMENDATION 8
We recommend against vertebroplasty for patients who present with an osteoporotic
spinal compression fracture on imaging with correlating clinical signs and symptoms and
who are neurologically intact.
Quality of
Quantity of
Critical
Evidence
Evidence
Downgrade
Outcome(s)
Strength of Recommendation: Strong
Description: Evidence is based on two or more "High" strength studies with consistent
findings for recommending for or against the intervention. A Strong recommendation
means that the benefits of the recommended approach clearly exceed the potential harm
(or that the potential harm clearly exceeds the benefits in the case of a strong negative
recommendation), and that the strength of the supporting evidence is high.
Implications: Practitioners should follow a Strong recommendation unless a clear and
compelling rationale for an alternative approach is present.
Rationale
There are two Level I studies that compare vertebroplasty to a sham procedure.1, 70 These studies report no statistically significant difference between the two procedures in pain using the VAS and function using the Roland Morris Disability scale (up to one month and six months respectively). These studies have been criticized for a variety of reasons. It has been argued that one of the trials1 was underpowered. However, this study did have sufficient power to detect the minimally clinically important (MCII) difference in pain (see Supporting Evidence section for details). Although crossover of patients after one month may have influenced the results in one of these studies,70 there was no crossover in the other study1 which also found no statistically significant or clinically important differences. Furthermore, crossover does not affect the lack of benefit for pain and function that the authors measured at one month. Another concern was the low participation rate of eligible patients. This is an issue of external validity (generalizability) and not internal validity. The work group discussed this flaw, but chose not to downgrade this study for applicability because the trial authors noted that the enrolled patients were comparable to patients seen in routine care.[ref] Furthermore, it has been proposed that vertebroplasty works better with certain fracture types than others. There are no prospective studies that report significant differences in outcomes based on fracture type. AAOS Clinical Practice Guidelines Unit It has also been proposed that vertebroplasty works better in patients that have more pain than those that were included in these trials. The baseline pain in both these trials was approximately 7 on a scale from 0 to 10. Other comparative studies had a baseline pain of about 8 and also had a mainly negative outcome.55, 71, 72 We recognize that a sham procedure may still introduce bias in the results (e.g. surgeons who know they are performing a sham procedure can unintentionally convey expectations to their patients) but there are also three other Level II studies that do not use a sham procedure as a control and they report similar results. One of these studies found clinically important pain relief at 24 hours.72 At six weeks pain relief was still statistically significant but not clinically important. After six weeks the effect was not statistically or clinically important (observations to two years). One study reported results for pain that were statistically significant and possibly clinically important at one day but inconclusive at two weeks.71 Another study found inconclusive results at three months.55 By making a strong recommendation against the use of vertebroplasty we are expressing our confidence that future evidence is unlikely to overturn the results of these trials. Supporting Evidence
Two studies with reliable data enrolling a total of 209 patients compared vertebroplasty to placebo.1, 70 One study included patients with subacute fractures (9 weeks since injury),1 while the other included chronic fractures (18 weeks).70 In the study of patients with subacute fractures, after the surgery all participants received usual care according to the discretion of the treating physician.1 In the study of patients with chronic fractures, patients were allowed to cross over to the alternative treatment after one month.70 There were no significant differences in pain, function, or quality of life in either study Three additional studies with moderately reliable data enrolling a total of 210 patients compared vertebroplasty to conservative treatment.55, 71, 72 Two studies were of patients with acute injuries, 55, 72 while the other included patients with subacute injuries (mean time after injury 11.6 weeks).71 In the randomized trial of patients with acute injuries, patients in both groups were offered pain medication and physiotherapy, while only patients in the conservative group were offered brace treatment.55 In the non-randomized trial of patients with acute injuries, all patients were offered similar analgesia and osteoporosis medications.72 In the randomized trial of patients with subacute injuries, patients were treated with pain medication according to individual needs.71 Pain was significantly reduced for one day in the vertebroplasty group, but not for longer durations (the significant result at 6 weeks is not clinically important). Function was improved for 2 weeks in one study and 6 weeks in another, but was no longer significant beyond 6 months. Quality of life and analgesic use favored the vertebroplasty group at 2 weeks. Fracture-related mortality was significantly reduced in the vertebroplasty group, but overall mortality was not- AAOS Clinical Practice Guidelines Unit Power calculations referenced in Rationale:While the study's a priori power analysis indicated that the study was powered to detect a between-group difference in pain of 2.5 units on VAS, further analysis indicated that the study was also powered sufficiently to detect the minimally clinically important difference of 1.5 units on VAS. Using the study's baseline standard deviation of 2.2 units, the minimum sample size required to have sufficient power to detect a 1.5 unit difference was 35 patients per group. The study enrolled 38 patients in the vertebroplasty group and 40 patients in the placebo group. AAOS Clinical Practice Guidelines Unit SUMMARY OF EVIDENCE
Table 69 Summary of Vertebroplasty Outcomes
months months months months
Dallas Pain Questionnaire (all subtests) Pain Bothersome Index Pain Frequency Index Pain in bed at night Roland Morris Disability circle-vertebroplasty compared to placebo w/usual care; square-vertebroplasty compared to conservative treatment
green-clinically important in favor of vertebroplasty; blue-possibly clinically important in favor of vertebroplasty;
yellow-not clinically important in favor of vertebroplasty; red-statistically significant in favor of placebo/conservative;
grey-statistically significant; open-not statistically significant, X-underpowered study
AAOS Clinical Practice Guidelines Unit STUDY QUALITY
Table 70 Quality of Included Studies for Recommendation 8 - Randomized Trials
× = Not Reported Duration
Treatments
Evidence
Vertebroplasty vs. Vertebroplasty vs. Vertebroplasty vs. SF-36 (physical) DPQ (anxiety and Vertebroplasty vs. Vertebroplasty vs. DPQ (daily activities) Vertebroplasty vs. DPQ (social interest) Vertebroplasty vs. Vertebroplasty vs. AAOS Clinical Practice Guidelines Unit Table 70 Quality of Included Studies for Recommendation 8 - Randomized Trials
× = Not Reported Duration
Treatments
Evidence
Vertebroplasty vs. Vertebroplasty vs. Vertebroplasty vs. Vertebroplasty vs. Vertebroplasty vs. Roland-Morris score Vertebroplasty vs. Vertebroplasty vs. Vertebroplasty vs. Vertebroplasty vs. AAOS Clinical Practice Guidelines Unit Table 70 Quality of Included Studies for Recommendation 8 - Randomized Trials
× = Not Reported Duration
Treatments
Evidence
Vertebroplasty vs. Vertebroplasty vs. Vertebroplasty vs. Vertebroplasty vs. Vertebroplasty vs. Vertebroplasty vs. Vertebroplasty vs. Vertebroplasty vs. Vertebroplasty vs. AAOS Clinical Practice Guidelines Unit Table 70 Quality of Included Studies for Recommendation 8 - Randomized Trials
× = Not Reported Duration
Treatments
Evidence
Vertebroplasty vs. Vertebroplasty vs. Vertebroplasty vs. Vertebroplasty vs. Roland-Morris score Vertebroplasty vs. Roland-Morris score Vertebroplasty vs. Roland-Morris score Vertebroplasty vs. Roland-Morris score Vertebroplasty vs. Vertebroplasty vs. AAOS Clinical Practice Guidelines Unit Table 70 Quality of Included Studies for Recommendation 8 - Randomized Trials
× = Not Reported Duration
Treatments
Evidence
Vertebroplasty vs. Vertebroplasty vs. Vertebroplasty vs. Pain Bothersomeness Vertebroplasty vs. Vertebroplasty vs. Pain Frequency Index Vertebroplasty vs. Roland-Morris score Vertebroplasty vs. Roland-Morris score Vertebroplasty vs. Roland-Morris score Vertebroplasty vs. Vertebroplasty vs. AAOS Clinical Practice Guidelines Unit Table 71 Quality of Included Studies for Recommendation 8 - Prospective Comparative Study
× = Not Reported Duration
Treatments
Evidence
Vertebroplasty vs. Vertebroplasty vs. Vertebroplasty vs. AAOS Clinical Practice Guidelines Unit VERTEBROPLASTY VS. PLACEBO
Figure 6 Vertebroplasty vs. Placebo – Difference in Pain
Figure 7 Vertebroplasty vs. Placebo – Difference in Physical Function
AAOS Clinical Practice Guidelines Unit Table 72 Vertebroplasty vs. Placebo - Pain
Difference
Clinically
Duration
between groups
Evidence
Important?
(95% CI)*
-0.4 (-1.5, 0.5) -0.7 (-1.8, 0.4) -0.2 (-1.5, 1.1) -0.1 (-1.3, 1.1) -0.2 (-1.6, 1.1) *Baseline-adjusted differences AAOS Clinical Practice Guidelines Unit Table 73 Vertebroplasty vs. Placebo – Physical Function
Difference between
Clinically
Duration
Evidence
groups (95% CI)*
Important?
-0.9 (-2.7, 0.8) -2.1 (-5.2, 0.9) -0.6 (-2.4, 1.2) Disability (RMD) -1.5 (-4.8, 1.7) *Baseline-adjusted differences Table 74 Vertebroplasty vs. Placebo – Physical and Mental Health
Difference
Clinically
Duration
Evidence
groups (95%
Important?
SF-36 Physical Component SF-36 Mental Component *Baseline-adjusted differences Table 75 Vertebroplasty vs. Placebo – Analgesic Use
Time After
Duration
OR (95% CI)*
Evidence
1.15 (0.98, 1.35) *Baseline-adjusted differences AAOS Clinical Practice Guidelines Unit Table 76 Vertebroplasty vs. Placebo – Quality of Life
Difference
Clinically
Duration
between groups
Evidence
Important?
(95% CI)*
0.05 (-0.01, 0.11) Quality of Life) -4.0 (-7.8, -0.2) *Baseline-adjusted differences
Table 77 Vertebroplasty vs. Placebo – Adverse Events
Duration
Evidence
Adverse Events (other than incident fractures) AAOS Clinical Practice Guidelines Unit VERTEBROPLASTY VS. CONSERVATIVE
Figure 8 Vertebroplasty vs. Conservative – Difference in Pain
Figure 9 Vertebroplasty vs. Conservative – Difference in Physical Function (Barthel Index)
AAOS Clinical Practice Guidelines Unit Table 78 Vertebroplasty vs. Conservative - Pain
Difference
Clinically
Duration
between groups
Evidence
Important?
0.4 (-0.3, 1.1)* 0.4 (-0.1, 0.9)* *Study used 0-25 scale; data has been normalized to 0-10 scale; Voormolen and Rousing studies lacked sufficient power to detect large effect for each non-significant outcome Table 79.Vertebroplasty vs. Conservative – Physical Function
Difference
Clinically
Duration
between groups
Evidence
Important?
AAOS Clinical Practice Guidelines Unit Table 80 Vertebroplasty vs. Conservative – Quality of Life
Difference
Time After
Clinically
Duration
between groups
Evidence
Important?
Table 81 Vertebroplasty vs. Conservative – Physical and Mental Health
Difference
Clinically
Duration
between groups
Evidence
Important?
SF-36 Physical Component 4.7 (-1.2, 10.6) SF-36 Mental Component 2.7 (-5.6, 11.0) Dallas Pain Questionnaire -10.3 (-32.9, 12.3) (DPQ) daily activities DPQ work and leisure -20.7 (-41.9, 0.5) DPQ anxiety and depression -11.3 (-35.1, 12.5) DPQ social interest -6.6 (-25.4, 12.2) Study lacked sufficient power to detect large effect for each outcome Table 82 Vertebroplasty vs. Conservative – Analgesic Use
Difference
Clinically
Duration
between groups
Evidence
Important?
AAOS Clinical Practice Guidelines Unit Table 83 Vertebroplasty vs. Conservative – Adverse Events
Vertebroplasty Conservative
Hazard Ratio
Duration
Evidence
Shaded cell indicates favored treatment AAOS Clinical Practice Guidelines Unit RECOMMENDATION 9
Kyphoplasty is an option for patients who present with an osteoporotic spinal
compression fracture on imaging with correlating clinical signs and symptoms and who
are neurologically intact.
Quality of
Quantity of
Critical
Evidence
Evidence
Downgrade
Outcome(s)
Strength of Recommendation: Limited
Description: Evidence from two or more "Low" strength studies with consistent findings,
or evidence from a single "Moderate" quality study recommending for or against the
intervention or diagnostic. A Limited recommendation means the quality of the
supporting evidence that exists is unconvincing, or that well-conducted studies show little
clear advantage to one approach versus another.
Implications: Practitioners should exercise clinical judgment when following a
recommendation classified as Limited, and should be alert to emerging evidence that
might negate the current findings. Patient preference should have a substantial
influencing role.
Rationale
Two Level II studies examined the use of kyphoplasty compared to conservative treatment.54, 73 One study examined subacute fractures54 while the other study examined chronic fractures.73 In the study of patients with subacute fractures, clinically important benefits in pain were found at 1 week and 1 month, with possibly important effects at 3 and 6 months. There was no clinically important benefit in pain at 12 months. The study also found possibly clinically important benefits in physical function (at 1 and 3 months only) and the SF-36 physical component score (at 1, 3, and 6 months only). Clinically important improvement in quality of life was present at 1 month, and it was possibly clinically important at 3, 6, and 12 months. In the chronic fractures study, all patients had fractures that were greater than one year old, raising the question as to whether the fracture was responsible for all of the pain. There was a statistically significant and possibly clinically important improvement in pain at 3, 6 and 12 months. There were also three Level II studies which compared kyphoplasty to vertebroplasty.60, 61, 74 These studies were inconsistent in design and outcome. In the first study, patients were treated at a median of 8 weeks after a fracture.60 No conservative treatment control group was included. Kyphoplasty was favored over vertebroplasty when pain was measured out to two years. Repeat kyphoplasty in this study was a confounding factor. In AAOS Clinical Practice Guidelines Unit the second study 21 patients were treated.74 Both groups experienced similar pain relief at 6 months, although there was insufficient power to find a difference. In the third and most recent study, 100 patients received either kyphoplasty or vertebroplasty within 43 days of fracture.61 There was no difference in pain outcomes between the treatment groups at 3 days and 6 months. When considering the technical similarities between kyphoplasty and vertebroplasty and the unique recommendations for their use within this guideline, several points deserve mention. • The comparison of vertebroplasty to a sham procedure confirms the lack of benefit from vertebroplasty for critical outcomes. • Both procedures were compared to similar control groups. In the case of kyphoplasty the comparison to conservative treatment resulted in possible clinically important differences for critical outcomes up to 12 months whereas vertebroplasty compared to conservative treatment showed only possible clinically important differences for critical outcomes at 1 day. • The direct comparison between vertebroplasty and kyphoplasty is logically consistent with the previous two points in as much as it shows a possibly clinically important advantage in critical outcomes for kyphoplasty at durations up to 2 years. These points alone merit a moderate strength recommendation for kyphoplasty due to the two Level II studies which compared kyphoplasty to conservative treatment. However, the comparisons between vertebroplasty and kyphoplasty are important. The results of the direct comparisons between kyphoplasty and vertebroplasty are not repeated across all studies which lowers our confidence that future studies will confirm the results of the current evidence. Thus, the recommendation is downgraded from moderate to limited and kyphoplasty is an option, for patients who present with an osteoporotic spinal compression fracture on imaging with correlating clinical signs and symptoms and who are neurologically intact. Supporting Evidence
Two studies with moderately reliable data enrolling a total of 360 patients compared kyphoplasty to conservative treatment.54, 73 One study was of patients with 6 weeks since injury,54 while the other study was of patients with a chronic injury (>12 months).73 In the study of patients with an acute injury, all participants received analgesics, bed rest, braces, physiotherapy, rehabilitation programs, and walking aids according to each hospital's standard practice.54 In the study of patients with a chronic injury, all patients received calcium, vitamin D, an oral amino-bisphosphonate, regular physiotherapy, and pain medication.73 In both studies, pain was reduced significantly more in the kyphoplasty group for 12 months, while function was improved for at least 6 months. Quality of life was measured in one study, and it was improved for 12 months in the kyphoplasty gr AAOS Clinical Practice Guidelines Unit Three additional studies with moderately reliable data enrolling a total of 172 patients compared kyphoplasty with vertebroplasty.60, 61, 74 One study included patients with acute fractures (2 weeks since injury),61 another included patients with subacute fractures (8 weeks),60 and the third included patients with time to injury of less than 6 months.74 Only one study reported clinically important differences in pain (subacute fractures study), and the results favored kyphoplasty. There were no significant differences in functi- AAOS Clinical Practice Guidelines Unit SUMMARY OF EVIDENCE
Table 84 Summary of Kyphoplasty Outcomes
Roland Morris Disability EVOS Physical Function Restricted Activity square-kyphoplasty compared to conservative treatment; circle-kyphoplasty compared to vertebroplasty;
green-clinically important in favor of kyphoplasty; blue-possibly clinically important in favor of kyphoplasty;
yellow-not clinically important in favor of kyphoplasty;
red-not clinically important in favor of vertebroplasty
grey-statistically significant; open-not statistically significant, X-underpowered study
AAOS Clinical Practice Guideline Unit STUDY QUALITY
Table 85 Quality of Included Studies for Recommendation 9 - Randomized Trials
× = Not Reported Duration
Treatments
Evidence
AAOS Clinical Practice Guideline Unit Table 85 Quality of Included Studies for Recommendation 9 - Randomized Trials
× = Not Reported Duration
Treatments
Evidence
Days of Restricted Days of Restricted Days of Restricted Days of Restricted AAOS Clinical Practice Guideline Unit Table 85 Quality of Included Studies for Recommendation 9 - Randomized Trials
× = Not Reported Duration
Treatments
Evidence
SF-36 (physical) AAOS Clinical Practice Guideline Unit Table 85 Quality of Included Studies for Recommendation 9 - Randomized Trials
× = Not Reported Duration
Treatments
Evidence
SF-36 (physical) SF-36 (physical) SF-36 (physical) AAOS Clinical Practice Guideline Unit Table 86 Quality of Included Studies for Recommendation 9 - Prospective Comparative Studies
× = Not Reported Duration
Treatments
Evidence
Vertebroplasty vs. Vertebroplasty vs. Vertebroplasty vs. AAOS Clinical Practice Guideline Unit Table 86 Quality of Included Studies for Recommendation 9 - Prospective Comparative Studies
× = Not Reported Duration
Treatments
Evidence
Vertebroplasty vs. Vertebroplasty vs. Vertebroplasty vs. Vertebroplasty vs. Vertebroplasty vs. Vertebroplasty vs. Vertebroplasty vs. Vertebroplasty vs. Vertebroplasty vs. Vertebroplasty vs. AAOS Clinical Practice Guideline Unit KYPHOPLASTY VS. CONSERVATIVE
Figure 10 Kyphoplasty vs. Conservative – Difference in Pain
Figure 11 Kyphoplasty vs. Conservative – Difference in Physical Function (Roland-Morris
Disability)
AAOS Clinical Practice Guideline Unit Table 87 Kyphoplasty vs. Conservative - Pain
Difference
Time After
Clinically
Duration
Evidence
groups (95%
Important?
*Baseline-adjusted difference; 3 month data from Grafe study is from interim report75 Table 88 Kyphoplasty vs. Conservative - Physical Function
Difference
Time After
Clinically
Duration
between groups
Evidence
Important?
10.6 (0.9, 20.3) 10.2 (-1.0, 21.4) *Baseline-adjusted difference AAOS Clinical Practice Guideline Unit Table 89 Kyphoplasty vs. Conservative - SF-36 Physical Component Score (PCS)
Difference
Time After
Clinically
Duration
between groups
Evidence
Important?
1.5 (-0.8, 3.9)* *Baseline-adjusted difference Table 90 Kyphoplasty vs. Conservative – Quality of Life
Difference
Clinically
Duration
between groups
Evidence
Important?
0.18 (0.08, 0.28)* 0.10 (0.02, 0.18) 0.12 (0.04, 0.20) 0.12 (0.01, 0.22)* *Baseline-adjusted difference AAOS Clinical Practice Guideline Unit Table 91 Kyphoplasty vs. Conservative – Restricted Activity
Difference
Time After
Clinically
Duration
between groups
Evidence
Important?
1.6 (-0.1, 3.3)* *Baseline-adjusted difference Table 92 Kyphoplasty vs. Conservative – Opioid Use
Time After
Kyphoplasty
Duration
Evidence
0.66 (0.37, 1.17) 0.48 (0.27, 0.85) 0.43 (0.24, 0.76) 0.59 (0.33, 1.04) 0.76 (0.40, 1.41) Shaded cell indicates favored treatment Table 93 Kyphoplasty vs. Conservative – Adverse Events
Time After
Kyphoplasty
Duration
Evidence
1.63 (0.83, 3.24) 1.14 (0.70, 1.88) AAOS Clinical Practice Guideline Unit KYPHOPLASTY VS. VERTEBROPLASTY
Figure 12 Kyphoplasty vs. Vertebroplasty - Difference in Pain
Figure 13 Kyphoplasty vs. Vertebroplasty - Difference in Physical Function
AAOS Clinical Practice Guideline Unit Table 94 Kyphoplasty vs. Vertebroplasty - Pain
Difference
Clinically
Duration
between groups
Evidence
Important?
-0.4 (-1.3, 0.5) -0.5 (-1.7, 0.7)* -0.1 (-0.8, 0.7) -0.3 (-0.5, -0.1) -0.1 (-0.7, 0.4) Both the De Negri and Grohs studies lacked sufficient power to detect a large effect for each non-significant outcome; *from median and range Table 95 Kyphoplasty vs. Vertebroplasty – Physical Function
Time After
Difference between
Clinically
Duration
Evidence
groups (95% CI)
Important?
4.0 (-1.9, 9.9)* 2.5 (-3.0, 8.0)* -2.0 (-8.4, 4.4)* Both studies lacked sufficient power to detect a large effect for each outcome; *from median and range AAOS Clinical Practice Guideline Unit RECOMMENDATION 10
We are unable to recommend for or against improvement of kyphosis angle in the
treatment of patients who present with an osteoporotic spinal compression fracture on
imaging with correlating clinical signs and symptoms.
Strength of Recommendation: Inconclusive
Description: Evidence from a single low quality study or conflicting findings that do not
allow a recommendation for or against the intervention. An Inconclusive
recommendation means that there is a lack of compelling evidence resulting in an unclear
balance between benefits and potential harm.
Implications: Practitioners should feel little constraint in following a recommendation
labeled as Inconclusive, exercise clinical judgment, and be alert for emerging evidence
that clarifies or helps to determine the balance between benefits and potential harm.
Patient preference should have a substantial influencing role.
Rationale
We found no study which addressed sagittal balance correction and properly correlated
kyphosis angle with any patient-oriented outcome. All studies retrieved for this
recommendation either examined only a single vertebrae as opposed to regional kyphosis
or did not report the correlation between a change in kyphosis angle and a change in any
patient-oriented outcome.
Supporting Evidence
We found no studies which examined the correlation between a change in regional kyphosis angle and any patient-oriented outcome. AAOS Clinical Practice Guideline Unit
RECOMMENDATION 11
We are unable to recommend for or against any specific treatment for patients who
present with an osteoporotic spinal compression fracture on imaging with correlating
clinical signs and symptoms and who are not neurologically intact.
Strength of Recommendation: Inconclusive
Description: Evidence from a single low quality study or conflicting findings that do not
allow a recommendation for or against the intervention. An Inconclusive
recommendation means that there is a lack of compelling evidence resulting in an unclear
balance between benefits and potential harm.
Implications: Practitioners should feel little constraint in following a recommendation
labeled as Inconclusive, exercise clinical judgment, and be alert for emerging evidence
that clarifies or helps to determine the balance between benefits and potential harm.
Patient preference should have a substantial influencing role.
Rationale
Patients who present with neurological symptoms and osteoporotic spinal compression fractures clearly require treatment because they face pain, diminished function, and increased mortality.68 However, despite the need to treat such patients, there is an absence of studies that examine which treatments are most effective for these patients. Therefore, we are unable to recommend for or against any specific treatment. Supporting Evidence
No studies met the inclusion criteria for this guideline. AAOS Clinical Practice Guideline Unit FUTURE RESEARCH
The work group realizes that the paucity of good quality research studies has limited the
strength of the recommendations. This underscores the necessity for further work in this
area. In particular, we hope that Level I studies are carried out to determine the
effectiveness of modalities such as bracing, physical therapy/exercise, and kyphoplasty in
the treatment of these fractures.
Our review suggests that radiographic fracture is not a reliable surrogate measure of symptomatic fracture. In many of the studies we reviewed the presence of a radiographic fracture, even if chronic, was postulated to be the source of back pain symptoms with no clear rational for that determination. This emphasizes the need for long term prospective studies on the natural history of osteoporotic spinal insufficiency fractures. There are comments in the literature about various fracture parameters such as type, location, degree of kyphosis, etc. as being clinically important. Unfortunately, this has not been adequately studied. Guidelines are living documents. Based on the fluid nature of guidelines, the work group anticipates that future research will address some of the recommendations in this guideline. We welcome further well-designed high quality research that will help clarify the recommendations in this guideline. We also welcome the opportunity to review the literature again in the future. The work group hopes that additional good quality studies will become available to address some of the many inadequately and unanswered questions in this guideline. AAOS Clinical Practice Guideline Unit IV. APPENDIXES
AAOS Clinical Practice Guideline Unit APPENDIX I
Seattle, WA 98105 WORK GROUP
Stephen I Esses, MD, Chair
Southwest Orthopedic Group Evidence Based Practice Committee Chair 6560 Fannin St Ste 1016 Michael Keith, MD
Houston TX 77030-2761 2500 Metro Health Drive Cleveland, OH 44109-1900 Robert McGuire, MD, Vice-Chair
University of Mississippi Medical Center AAOS Staff: Department of Orthopedic Surgery Charles M. Turkelson, PhD
Director of Research and Scientific Affairs Jackson MS 39216-4500 6300 N. River Rd, Suite 503 Rosemont, IL 60018 John Jenkins, MD
University of Mississippi Medical Center Janet L. Wies, MPH
Division of Rheumatology, Dept of AAOS Clinical Practice Guideline Manager Patrick Sluka, MPH
Jackson MS 39216-4500 AAOS Research Analyst Joel Finkelstein, MD
Kevin M. Boyer
2075 Bayview Ave MG361 AAOS Research Analyst Toronto ON M4N3M Kristin Hitchcock, MLS
Eric Woodard, MD
AAOS Medical Librarian New England Baptist Hospital 125 Parker Hill Ave. Special Acknowledgements Sara Anderson, MPH Laura Raymond, MA Guidelines and Technology Oversight Chair William C. Watters III MD
6624 Fannin #2600 Houston, TX 77030 Guidelines and Technology Oversight Vice-Chair Michael J. Goldberg, MD
Department of Orthopaedics Seattle Children's Hospital 4800 Sand Point Way NE AAOS Clinical Practice Guideline Unit APPENDIX II
AAOS BODIES THAT APPROVED THIS CLINICAL PRACTICE GUIDELINE

Guidelines and Technology Oversight Committee
The AAOS Guidelines and Technology Oversight Committee (GTOC) consists of sixteen
AAOS members. The overall purpose of this Committee is to oversee the development of
the clinical practice guidelines, performance measures, health technology assessments
and utilization guidelines.
Evidence Based Practice Committee
The AAOS Evidence Based Practice Committee (EBPC) consists of ten AAOS members.
This Committee provides review, planning and oversight for all activities related to
quality improvement in orthopaedic practice, including, but not limited to evidence-based
guidelines, performance measures, and outcomes.
Council on Research, Quality Assessment, and Technology
To enhance the mission of the AAOS, the Council on Research, Quality Assessment, and
Technology promotes the most ethically and scientifically sound basic, clinical, and
translational research possible to ensure the future care for patients with musculoskeletal
disorders. The Council also serves as the primary resource to educate its members, the
public, and public policy makers regarding evidenced-based medical practice,
orthopaedic devices and biologics, regulatory pathways and standards development,
patient safety, occupational health, technology assessment, and other related areas of
importance.
The Council is comprised of the chairs of the AAOS Biological Implants, Biomedical Engineering, Evidence Based Practice, Guidelines and Technology Oversight, Occupational Health and Workers' Compensation, Patient Safety, Research Development, and US Bone and Joint Decade committees. Also on the Council are the AAOS second vice-president, representatives of the Diversity Advisory Board, the Women's Health Issues Advisory Board, the Board of Specialty Societies (BOS), the Board of Councilors (BOC), the Communications Cabinet, the Orthopaedic Research Society (ORS), the Orthopedic Research and Education Foundation (OREF), and three members at large. Board of Directors
The 17 member AAOS Board of Directors manages the affairs of the AAOS, sets policy,
and determines and continually reassesses the Strategic Plan.
AAOS Clinical Practice Guidelines Unit DOCUMENTATION OF APPROVAL
AAOS Work Group Draft Completed Peer Review Completed Public Commentary Completed AAOS Guidelines and Technology Oversight Committee September 3, 2010 AAOS Evidence Based Practice Committee September 3, 2010 AAOS Council on Research Quality Assessment September 7, 2010 AAOS Board of Directors September 24, 2010 AAOS Clinical Practice Guidelines Unit APPENDIX III
STUDY ATTRITION FLOWCHART
6521 citations identified by literature search 1956 citations excluded 4565 abstracts screened for inclusion 3854 abstracts excluded 711 articles recalled for full text review 661 articles excluded 50 articles included AAOS Clinical Practice Guidelines Unit APPENDIX IV
LITERATURE SEARCHES
Search Strategy for PubMed/MEDLINE #1 "Fractures, Compression"[mh] OR ((compression[tiab] OR insufficiency[tiab] OR collaps*[tiab] OR osteoporo*[tiab] OR pathologic*[tiab]) AND (fracture*[tiab] OR "Spinal Fractures"[mh]) AND (spine[tiab] OR spinal[tiab] OR vertebr*[tiab] OR dorsolumbar[tiab] OR lumbar[tiab] OR "Lumbar Vertebrae"[mh] OR thoracic[mh] OR "Thoracic Vertebrae"[mh] OR "spinal injuries"[mh])) #2 "Bed rest"[mh] OR (bed[tiab] AND rest[tiab]) OR "Physical Therapy Modalities"[mh] OR "physical therapy" OR physiotherap*[tiab] OR brace[tiab] OR bracing[tiab] OR "Complementary Therapies"[mh] OR acupuncture[tiab] OR magnet[tiab] OR magnets[tiab] OR "Electric stimulation"[mh] OR (electric*[tiab] AND stimulat*[tiab]) OR complementary[tiab] OR alternative[tiab] OR drug therapy[sh] OR Analgesics[mh] OR analgesics[pa] OR NSAID[tiab] OR opioid*[tiab] OR (muscle[tiab] AND relax*[tiab]) OR "Muscle Relaxants, Central"[mh] OR acetaminophen[tiab] OR naproxen[tiab] OR ibuprofen[tiab] OR hydrocodone[tiab] OR oxycodone[tiab] OR oxycontin[tiab] OR morphine[tiab] OR benzodiazepine*[tiab] OR tramadol[tiab] OR Steroids[mh] OR steroid*[tiab] OR prednisone[tiab] OR Glucocorticoids[mh] OR Glucocorticoids[pa] OR solumedrol[tiab] OR fentanyl[tiab] OR lidoderm[tiab] OR aspirin[tiab] OR codeine[tiab] OR "Bone Density Conservation Agents"[mh] OR "Bone Density Conservation Agents"[pa] OR Diphosphonates[mh] OR bisphosphonate*[tiab] OR alendronate[tiab] OR fosamax[tiab] OR calcitonin[tiab] OR surgery[sh] OR surgical[tiab] OR surgery[tiab] OR repair*[tiab] OR "Orthopedic procedures"[mh] OR (percutaneous[tiab] AND vertebral[tiab] AND augmentation[tiab]) OR PMMA[tiab] OR " Polymethyl Methacrylate"[substance] OR (polymethyl[tiab] AND methacrylate[tiab]) OR Vertebroplasty[mh] OR vertebroplasty[tiab] OR kyphoplasty[tiab] OR "Bone Cements"[mh] OR "Bone Cements"[pa] OR BMP[tiab] OR (bone[tiab] AND morphogenic[tiab] AND (protein[tiab] OR proteins[tiab])) #3 English[lang] AND 1966:2009[pdat] NOT (animal[mh] NOT human[mh]) NOT ((child[mh] OR infant[mh] OR adolescent[mh]) NOT adult[mh]) NOT (cadaver[mh] OR "in vitro"[pt] OR comment[pt] OR editorial[pt] OR letter[pt] OR addresses[pt] OR news[pt] OR "newspaper article"[pt] OR "historical article"[pt] OR "case report"[title]) #5 Medline[tw] OR systematic review[tiab] OR Meta-analysis[pt] #7 "Clinical Trial"[pt] OR (clinical[tiab] AND trial[tiab]) OR random*[tw] OR "Therapeutic use"[sh] #8 (#4 AND #7) NOT #5 #9 #4 NOT (#7 OR #5) AAOS Clinical Practice Guidelines Unit Search strategy for EMBASE #1 'Compression fracture'/de OR ((compression OR insufficiency OR collaps* OR osteoporo* OR pathologic*) AND (fracture* OR 'Spine fracture'/de) AND (spine OR spinal OR vertebr* OR dorsolumbar OR lumbar OR 'lumbar vertebra'/de OR thoracic OR vertebra/de OR 'spine injury'/de)) #2 'bed rest'/de OR (bed AND rest) OR 'physical medicine'/exp OR 'physical therapy' OR physiotherap* OR brace OR bracing OR 'alternative medicine'/de OR acupuncture/de OR acupuncture OR magnet OR 'nonsteroid antiinflammatory agent'/exp OR 'narcotic analgesic agent'/exp OR opioid* OR 'muscle relaxant agent'/exp OR (muscle AND relax*) OR acetaminophen OR naproxen OR ibuprofen OR hydrocodone OR oxycodone OR oxycontin OR morphine OR benzodiazepine* OR tramadol OR steroid* OR prednisone OR steroid/exp OR solumedrol OR fentanyl OR lidoderm OR aspirin OR codeine OR 'bone density conservation agent'/de OR bisphosphonate* OR 'bisphosphonic acid derivative'/exp OR alendronate OR fosamax OR calcitonin OR surgical OR surgery OR repair* OR 'orthopedic surgery'/exp OR 'percutaneous vertebral augmentation' OR PMMA OR 'poly(methyl methacrylate)'/de OR 'polymethyl methacrylate' OR 'percutaneous vertebroplasty'/de OR vertebroplasty OR kyphoplasty/de OR kyphoplasty OR 'bone cement'/exp OR BMP OR 'bone morhpogenic protein*' OR 'bone morphogenetic protein'/de #3 [english]/lim AND [humans]/lim AND [embase]/lim NOT (cadaver/de OR 'in vitro study'/exp OR ‘case report':ti OR 'abstract report'/de OR book/de OR editorial/de OR letter/de OR note/de) #5 ('meta analysis' OR 'systematic review' OR medline) #7 random* OR 'clinical trial' OR 'health care quality'/exp #8 (#4 AND #7) NOT #5 #9 #4 NOT (#7 OR #5) AAOS Clinical Practice Guidelines Unit Search Strategy for CINAHL S1 ( compression OR insufficiency OR collaps* OR osteoporo* OR pathologic* ) and ( fracture* OR MH "Spinal Fractures" ) and ( spine OR spinal OR vertebr* OR dorsolumbar OR lumbar OR MH "Lumbar Vertebrae" OR MH "Thoracic Vertebrae" OR thoracic OR MH "Spinal Injuries" ) S2 MH "Fractures, Compression" S4 MH "bed rest" OR "bed rest" OR MH "Bed Rest Care (Iowa NIC)" OR MH "Physical Therapy +" OR "physical therapy" OR physiotherapy* OR MH "Orthoses" OR brace OR bracing OR MH "Alternative Therapies +" OR acupuncture OR magnet OR magnets OR MH "Electric Stimulation" OR "electric stimulat*" OR MH "acupuncture +" OR MH "Analgesics, Opioid +" OR NSAID OR opioid* OR MH "Antiinflammatory Agents, Non-Steroidal +" OR MH "Muscle Relaxants, Central +" OR "muscle relax*" OR acetaminophen OR naproxen OR ibuprofen OR hydrocodone OR oxycodone OR oxycontin OR morphine OR benzodiazepine* OR tramadol OR MH "Steroids" OR steroid* OR prednisone OR solumedrol OR fentanyl OR lidoderm OR aspirin OR codeine OR MH "Diphosphonates +" OR fosamax OR alendronate OR calcitonin OR surgical OR surgery OR repair* OR MH "Orthopedic Surgery +" OR "percutaneous vertebral augmentation" OR PMMA OR "polymethyl methacrylate" OR vertebroplasty OR kyphoplasty OR MH "Bone Cements" OR BMP OR "bone morphogenic protein*" S5 LA English not (PT "editorial" or PT "letter" or PT "case study" or TI "case report") S7 "meta analysis" or PT "review" or PT "systematic review" S9 MH "treatment outcomes+" OR MH "experimental studies" OR random* Search strategy for Cochrane Library (spine OR spinal OR vertebr*) AND (compression OR insufficiency) AND fracture AND (surgery OR surgical OR repair OR treat* OR therap*) AAOS Clinical Practice Guidelines Unit APPENDIX V
DATA EXTRACTION ELEMENTS

The data elements below were extracted into electronic forms in Microsoft® Access. The
extracted information includes:
Study Characteristics
• methods of randomization and allocation • blinding of patients and evaluators • loss to follow-up • study design
Patient Characteristics
• patient inclusion/exclusion criteria • fracture classification
Results (for all relevant outcomes in a study)
• outcome measure • duration of follow up • mean or median • measure of dispersion • results of hypothesis testing AAOS Clinical Practice Guidelines Unit APPENDIX VI
JUDGING THE QUALITY OF TREATMENT STUDIES
RANDOMIZED CONTROLLED TRIALS Did the study employ stochastic randomization? Was there concealment of allocation? Were subjects blinded to the treatment they received? Were those who assessed/rated the patient's outcomes blinded to the group to which the patients were assigned? Was there more than 80% follow-up for all patients in the control group and the experimental group on the outcome of interest? Did patients in the different study groups have similar levels of performance on ALL of the outcome variables at the time they were assigned to groups? For randomized crossover studies, was there evidence that the results obtained in the study's two experimental groups (in period 1 and 2) did not differ? For randomized crossover studies, was there evidence that the results of the two control groups (in period 1 and 2) did not differ? PROSPECTIVE NON- RANDOMIZED CONTROLLED STUDIES Were the characteristics of patients in the different study groups comparable at the beginning of the study? Did patients in the different study groups have similar levels of performance on ALL of the outcome variables at baseline? Were all of the study's groups concurrently treated? Was there more than 80% follow-up for all patients in the control group and the experimental group on the outcome of interest? Did the study avoid collecting control group data from one center and experimental group data from another? For crossover studies, was there evidence that the results obtained in the study's two experimental groups (in period 1 and 2) did not differ? For crossover studies, was there evidence that the results of the two control groups (in period 1 and 2) did not differ? AAOS Clinical Practice Guidelines Unit RETROSPECTIVE COMPARATIVE STUDIES Was there less than 20% difference in completion rates in the study's groups? Were all of the study's groups concurrently treated? Was the same treatment given to all patients enrolled in the experimental and Were the same laboratory tests, clinical findings, psychological instruments, etc. used to measure the outcomes in all of the study's groups? Were the follow-up times in all of the study's relevant groups approximately equal? Was there more than 80% follow-up for all patients in the control group and the experimental group on the outcome of interest? Did the study avoid collecting control group data from one center and experimental group data from another? Did patients in the different study groups have similar levels of performance on ALL of the outcome variables at the time they were assigned to groups? Were the characteristics of patients in the different study groups comparable at the beginning of the study? Was enrollment in the study consecutive? Was there more than 80% follow-up for all patients on the outcome of interest? Were the same laboratory tests, clinical findings, psychological instruments, etc. used to measure the outcomes in all patients? Were the patients instructed/not given concomitant or adjuvant treatments? Were the follow-up times for all patients approximately equal? AAOS Clinical Practice Guidelines Unit OPINION-BASED RECOMMENDATIONS
A guideline can contain recommendations that are backed by little or no data. Under such circumstances, work groups often issue opinion-based recommendations. Although doing so is sometimes acceptable in an evidence-based guideline (expert opinion is a form of evidence), it is also important to avoid constructing a guideline that liberally uses expert opinion; research shows that expert opinion is often incorrect. Opinion-based recommendations are developed only if they address a vitally important aspect of patient care. For example, constructing an opinion-based recommendation in favor of taking a history and physical is warranted. Constructing an opinion-based recommendation in favor of a specific modification of a surgical technique is seldom warranted. To ensure that an opinion-based recommendation is absolutely necessary, the AAOS has adopted rules to guide the content of the rationales that underpin such recommendations. These rules are based on those outlined by the US Preventive Services Task Force (USPSTF).76 Specifically, rationales based on expert opinion must: • Not contain references to or citations from articles not included in the systematic review that underpins the recommendation. • Not contain the AAOS guideline language "We Recommend", "We suggest" or "treatment x is an option". • Contain an explanation of the potential preventable burden of disease. This involves considering both the incidence and/or prevalence of the disease, disorder, or condition and considering the associated burden of suffering. To paraphrase the USPSTF, when evidence is insufficient, provision of a treatment (or diagnostic) for a serious condition might be viewed more favorably than provision of a treatment (or diagnostic) for a condition that does not cause as much suffering. The AAOS (like the USPSTF) understand that evaluating the "burden of suffering" is subjective and involves judgment. This evaluation should be informed by patient values and concerns. The considerations outlined in this bullet make it difficult to recommend new technologies. It is not appropriate for a guideline to recommend widespread use of a technology backed by little data and for which there is limited experience. Such technologies are addressed in the AAOS' Technology Overviews. • Address potential harms. In general, "When the evidence is insufficient, an intervention with a large potential for harm (such as major surgery) might be viewed less favorably than an intervention with a small potential for harm (such as advice to watch less television)."76 • Address apparent discrepancies in the logic of different recommendations. Accordingly, if there are no relevant data for several recommendations and the work group chooses to issue an opinion-based recommendation in some cases AAOS Clinical Practice Guidelines Unit but chooses not to make a recommendation in other cases, the rationales for the opinion-based recommendations must explain why this difference exists. Information garnered from the previous bullet points will be helpful in this regard. • Consider current practice. The USPSTF specifically states that clinicians justifiably fear that not doing something that is done on a widespread basis will lead to litigation.76 The consequences of not providing a service that is neither widely available nor widely used are less serious than the consequences of not providing a treatment accepted by the medical profession and thus expected by patients. Discussions of available treatments and procedures rely on mutual communication between the patient's guardian and physician, and on weighing the potential risks and benefits for a given patient. The patient's "expectation of treatment" must be tempered by the treating physician's guidance about the reasonable outcomes that the patient can expect. • Justify, why a more costly device, drug, or procedure is being recommended over a less costly one whenever such an opinion-based recommendation is made. Work group members write the rationales for opinion based recommendations on the first day of the final work group meeting. When the work group re-convenes on the second day of its meeting, it will vote on the rationales. The typical voting rules will apply. If the work group cannot adopt a rationale after three votes, the rationale and the opinion-based recommendation will be withdrawn, and a "recommendation" stating that the group can neither recommend for or against the recommendation in question will appear in the guideline. Discussions of opinion-based rationales may cause some members to change their minds about whether to issue an opinion-based recommendation. Accordingly, at any time during the discussion of the rationale for an opinion-based recommendation, any member of the work group can make a motion to withdraw that recommendation and have the guideline state that the work group can neither recommend for or against the recommendation in question. CHECKLIST FOR VOTING ON OPINION-BASED RECOMMENDATIONS
When voting on the rationale, please consider the following: 1. Does the recommendation affect a substantial number of patients or address treatment (or diagnosis) of a condition that causes death and/or considerable suffering? 2. Does the recommendation address the potential harms that will be incurred if it is implemented and, if these harms are serious, does the recommendation justify; a. why the potential benefits outweigh the potential harms and/or AAOS Clinical Practice Guidelines Unit b. why an alternative course of treatment (or diagnostic workup) that involves less serious or fewer harms is not being recommended? 3. Does the rationale explain why the work group chose to make a recommendation in the face of minimal evidence while, in other instances, it chose to make no recommendation in the face of a similar amount of evidence? 4. Does the rationale explain that the recommendation is consistent with current 5. If relevant, does the rationale justify why a more costly device, drug, or procedure is being recommended over a less costly one? AAOS Clinical Practice Guidelines Unit APPENDIX VII
FORM FOR ASSIGNING STRENGTH OF RECOMMENDATION
(INTERVENTIONS)
GUIDELINE RECOMMENDATION _ PRELIMINARY STRENGTH OF RECOMMENDATION: LIST BENEFITS AND HARMS Please list the benefits (as demonstrated by the systematic review) of the intervention. Please list the harms (as demonstrated by the systematic review) of the intervention. Please list the benefits for which the systematic review is not definitive. Please list the harms for which the systematic review is not definitive. IDENTIFY CRITICAL OUTCOMES Please circle the above outcomes that are critical for determining whether the intervention is beneficial and whether it is harmful. Are data about critical outcomes lacking to such a degree that you would lower the preliminary strength of the recommendation? What is the resulting strength of recommendation? EVALUATE APPLICABILITY OF THE EVIDENCE Is the applicability of the evidence for any of the critical outcomes so low that substantially worse results are likely to be obtained in actual clinical practice? Please list the critical outcomes backed by evidence of doubtful applicability. Should the strength of recommendation be lowered because of low applicability? What is the resulting strength of recommendation? BALANCE BENEFITS AND HARMS Are there trade-offs between benefits and harms that alter the strength of recommendation obtained in STEP 3? What is the resulting strength of recommendation? AAOS Clinical Practice Guidelines Unit CONSIDER STRENGTH OF EVIDENCE Does the strength of the existing evidence alter the strength of recommendation obtained in STEP 4? What is the resulting strength of recommendation? NOTE: Because we are not performing a formal cost analyses, you should only consider costs if their impact is substantial. AAOS Clinical Practice Guidelines Unit APPENDIX VIII
VOTING BY THE NOMINAL GROUP TECHNIQUE
Voting on guideline recommendations will be conducted using a modification of the nominal group technique (NGT), a method previously used in guideline development.21 Briefly each member of the guideline work group ranks his or her agreement with a guideline recommendation on a scale ranging from 1 to 9 (where 1 is "extremely inappropriate" and 9 is "extremely appropriate"). Consensus is obtained if the number of individuals who do not rate a measure as 7, 8, or 9 is statistically non-significant (as determined using the binomial distribution). Because the number of work group members who are allowed to dissent with the recommendation depends on statistical significance, the number of permissible dissenters varies with the size of the work group. The number of permissible dissenters for several work group sizes is given in the table below: Number of Permissible
Work group Size
Dissenters
Not allowed, statistical significance cannot be The NGT is conducted by first having members vote on a given recommendation without discussion. If the number of dissenters is "permissible", the recommendation is adopted without further discussion. If the number of dissenters is not permissible, there is further discussion to see whether the disagreement(s) can be resolved. Three rounds of voting are held to attempt to resolve disagreements. If disagreements are not resolved after three voting rounds, no recommendation is adopted.
AAOS Clinical Practice Guidelines Unit
APPENDIX IX
STRUCTURED PEER REVIEW FORM
Review of any AAOS confidential draft allows us to improve the overall guideline but does not imply endorsement by any
given individual or any specialty society who participates in our review processes. The AAOS review process may result in
changes to the documents; therefore, endorsement cannot be solicited until the AAOS Board of Directors officially approves
the final guideline.
Reviewer Information:

Name of Reviewer _
Address _
City State _ Zip Code _
Phone _Fax _E-mail _
Specialty Area/Discipline: _
Work setting: _Credentials:


May we list you as a Peer Reviewer in the final Guidelines (GL)?
If you do not wish to be listed, your name will be removed for identification purposes.
However, your COI will still be available for review with the comments you have made.

Are you reviewing this guideline as a representative of a professional society?

If yes, may we list your society as a reviewer of this guideline?

Society Name: _
(Listing the specialty society as a reviewing society does not imply or otherwise indicate endorsement of this guideline.)

Conflicts of Interest (COI): All Reviewers must declare their conflicts of interest.
If the boxes below are not checked and/or the reviewer does not attach his/her conflicts of interest, the reviewer's comments will not be
addressed by the AAOS nor will the reviewer's name or society be listed as a reviewer of this GL. If a committee reviews the guideline,
only the chairperson/or lead of the review must declare their relevant COI.


I have declared my conflicts of interest on page 2 of this form.
I have declared my conflicts of interest in the AAOS database; my customer # is
I understand that the AAOS will post my declared conflicts of interest with my comments concerning review of
this guideline or technology overview on the AAOS website.
AAOS Clinical Practice Guidelines Unit REVIEWER CONFLICT OF INTEREST - The Orthopaedic Disclosure Program
Each item below requires an answer. Please report information for the last 12-months as required by the Accreditation
Council for Continuing Medical Education (ACCME) guidelines.

Do you or a member of your immediate family receive royalties for any pharmaceutical, biomaterial or
orthopaedic product or device?
If YES, please identify product or device:
Within the past twelve months, have you or a member of your immediate family served on the speakers
bureau or have you been paid an honorarium to present by any pharmaceutical, biomaterial or
orthopaedic product or device company?
If YES, please identify company: Are you or a member of your immediate family a PAID EMPLOYEE for any pharmaceutical, biomaterial or
orthopaedic device or equipment company, or supplier?
If YES, please identify company or supplier:
Are you or a member of your immediate family a PAID CONSULTANT for any pharmaceutical, biomaterial
or orthopaedic device or equipment company, or supplier?
If YES, please identify company or supplier:
Are you or a member of your immediate family an UNPAID CONSULTANT for any pharmaceutical,
biomaterial or orthopaedic device or equipment company, or supplier?
If YES, please identify company or supplier:
Do you or a member of your immediate family own stock or stock options in any pharmaceutical,
biomaterial or orthopaedic device or equipment company, or supplier (excluding mutual funds)
If YES, please identify company or supplier:
Do you or a member of your immediate family receive research or institutional support as a principal
investigator from any pharmaceutical, biomaterial or orthopaedic device or equipment company, or
supplier?
If YES, please identify company or supplier:
Do you or a member of your immediate family receive any other financial or material support from any
pharmaceutical, biomaterial or orthopaedic device and equipment company or supplier?
If YES, please identify company or supplier:
Do you or a member of your immediate family receive any royalties, financial or material support from any
medical and/or orthopaedic publishers?
If YES, please identify publisher:
Do you or a member of your immediate family serve on the editorial or governing board of any medical
and/or orthopaedic publication?
If YES, please identify:
Do you or a member of your immediate family serve on the Board of Directors or a committee of any
medical and/or orthopaedic professional society?
If YES, please identify: AAOS Clinical Practice Guidelines Unit Reviewer Instructions
Please read and review this Draft Clinical Practice Guideline and its associated Technical Report with particular focus on your area of
expertise. Your responses are confidential and will be used only to assess the validity, clarity and accuracy of the interpretation of the
evidence. If applicable, please specify the draft page and line numbers in your comments. Please feel free to also comment on the
overall structure and content of the guideline and Technical Report. If you need more space than is provided, please attach additional
pages.
Please complete and return this form electronically to [email protected] or fax the form back to Jan Wies at (847) 823-9769. Thank you
in advance for your time in completing this form and giving us your feedback. We value your input and greatly appreciate your efforts.
Please send the completed form and comments by end of day DATE.
Please indicate your level of agreement with each of the following statements by placing an "X" in the appropriate box.
Somewhat Somewhat
Disagree Disagree Agree Agree
1. The recommendations are clearly stated 2. There is an explicit link between the recommendations and the supporting evidence 3. Given the nature of the topic and the data, all clinically important outcomes are considered 4. The guideline's target audience is clearly described 5. The patients to whom this guideline is meant to apply are specifically 6. The criteria used to select articles for inclusion are appropriate 7. The reasons why some studies were excluded are clearly described 8. All important studies that met the article inclusion criteria are 9. The validity of the studies is appropriately appraised 10. The methods are described in such a way as to be reproducible. 11. The statistical methods are appropriate to the material and the objectives of this guideline 12. Important parameters (e.g., setting, study population, study design) that could affect study results are systematically addressed 13. Health benefits, side effects, and risks are adequately addressed 14. The writing style is appropriate for health care professionals. 15. The grades assigned to each recommendation are appropriate AAOS Clinical Practice Guidelines Unit COMMENTS
Please provide a brief explanation of both your positive and negative answers in the preceding section. If applicable, please specify the draft page and line numbers in your comments. Please feel free to also comment on the overall structure and content of the guideline and Technical Report OVERALL ASSESSMENT

Would you recommend these guidelines for use in practice? (check one)

Strongly recommend Recommend (with provisions or alterations) Would not recommend AAOS Clinical Practice Guidelines Unit APPENDIX X
PEER REVIEW PANEL
Participation in the AAOS peer review process does not constitute an endorsement
of this guideline by the participating organization.
Peer review of the draft guideline is completed by an outside Peer Review Panel. Outside peer reviewers are solicited for each AAOS guideline and consist of experts in the guideline's topic area. These experts represent professional societies other than AAOS and are nominated by the guideline work group prior to beginning work on the guideline. For this guideline, 23 outside peer review organizations were invited to review the draft guideline and all supporting documentation. Eight societies participated in the peer review of the Treatment of Symptomatic Osteoporotic Spinal Compression Fractures guideline draft and seven explicitly consented to be listed as a peer review organization in this appendix. The organizations that reviewed the document and consented to be listed as a peer review organization are listed below: American Academy of Physical Medicine and Rehabilitation (AAPMR)
American College of Radiology (ACR)
AO Spine International
International Spine Intervention Society (ISIS)
National Osteoporosis Foundation (NOF)
North American Spine Association (NASS)
Neurosurgery Washington Committee, American Association of Neurological
Surgeons/Congress of Neurological Surgeons (AANS/CNS)
Individuals who participated in the peer review of this document and gave their consent to be listed as reviewers of this document are: Professor Nikolai Bogduk MD ISIS
Christopher M. Bono MD NASS
Gary Ghiselli MD NASS
Bradford J Richmond MD ACR
Charles A. Reitman, MD AAOS GTOC
Paul Heini MD AO Spine
John Kirkpatrick MD AAOS EBPC
AAOS Clinical Practice Guidelines Unit Michael R. McClung, MD NOF
Ariz R. Mehta MD AAPMR
Mark E. Linskey, M.D. (as Chairman of the AANS/CNS Joint Guidelines
Committee)
Participation in the AAOS guideline peer review process does not constitute an
endorsement of the guideline by the participating organizations or the individuals
listed above nor does it is any way imply the reviewer supports this document.
AAOS Clinical Practice Guidelines Unit PUBLIC COMMENTARY
A period of public commentary follows the peer review of the draft guideline. If
significant non-editorial changes are made to the document as a result of public
commentary, these changes are also documented and forwarded to the AAOS bodies that
approve the final guideline.
Public commentators who gave explicit consent to be listed in this document include the
following:
None
Participation in the AAOS guideline public commentary review process does not
constitute an endorsement of the guideline by the participating organizations or the
individual listed nor does it in any way imply the reviewer supports this document.
AAOS Clinical Practice Guidelines Unit APPENDIX XI
INTERPRETING THE GRAPHS
LINE GRAPHS
Throughout the guideline we use line graphs to illustrate the differences in efficacy between the experimental and control groups of a study. Each point represents the difference between the two study groups for the designated outcome at that particular time point. A positive value indicates a better outcome (e.g., less pain) in the experimental group. The error bars represent the 95% Confidence Interval. The dotted line represents the Minimally Clinically Important Improvement (MCII) for the outcome. In the example below, the difference in pain between the calcitonin and placebo groups is compared at 4 time points in two separate studies (Lyritis 1997 and Lyritis 1999). For instance, at 4 weeks the pain on VAS in the calcitonin group is about 7 units less than the pain in the placebo group. The difference is statistically significant because the confidence intervals do not cross 0, and the difference is clinically important because the lower confidence interval is greater than the MCII value. Calcitonin vs. Placebo – Difference in Pain
AAOS Clinical Practice Guidelines Unit FOREST PLOTS
In Recommendation 2 we use descriptive diagrams known as forest plots to present data from studies comparing the differences in outcomes between two treatment groups. In cases where a meta-analysis has been performed (combining combining results of multiple studies into a single estimate of overall effect), the estimate of overall effect is presented at the bottom of the graph using a diamond to illustrate the confidence intervals of the estimated overall effect. In cases where a meta-analysis has not been performed, each point and corresponding horizontal line on a sample plot should be viewed independently. In the example below, the odds ratio is the effect measure used to depict differences in outcomes between the two treatment groups of a study. In other forest plots, the point can refer to other summary measures (such as the mean difference or relative risk). The horizontal line running through each point represents the 95% confidence interval for that point. In this graph, the solid vertical line represents "no effect" where the Odds Ratio, OR, is equal to one. When mean differences are portrayed, the vertical line of no effect is at zero. For example, in the figure below the odds of a patient experiencing Outcome 1 are 5.9 times greater for patients who received Treatment B than for patients who received Treatment A. This result is statistically significant because the 95% Confidence Interval does not cross the "no effect" line. In general, the plots are arranged such that results to the left of the "no effect" line favor Treatment A while results to the right favor Treatment B. In the example below, the odds ratio for Outcome 1 favors Treatment B, the odds ratio for Outcome 3 favors Treatment A, and the odds ratio for Outcome 2 does not favor either treatment because the 95% CI crosses the "no effect" line (i.e. the difference is not statistically significant). Odds Ratio (95% CI) 5.90 (3.38, 10.29) 0.72 (0.43, 1.19) 0.11 (0.06, 0.20) AAOS Clinical Practice Guidelines Unit ABBREVIATIONS USED IN THIS REPORT
95% confidence interval
American Academy of Orthopaedic Surgeons activities of daily living Assessment of Quality of Life AAOS Board of Councilors AAOS Board of Directors AAOS Board of Specialty Societies capacatively coupled electric field confidence interval Continuing Medical Education AAOS Council on Research, Quality Assessment, and Technology Dallas Pain Questionnaire evidence based medicine AAOS Evidence Based Practice Committee European Quality of Life – Five Dimensions European Vertebral Osteoporosis Study Grading of Recommendations, Assessment, Development, and uidelines and Te chnology Oversight Committee International Unit limitations of daily living minimal clinically important difference minimal clinically important improvement magnetic resonance imaging Nominal Group Technique numerical rating scale non-steroidal anti-inflammatory drug Oswestry Disability Index Osteoporosis Quality of Life Questionnaire Orthopedic Research and Education Foundation Orthopaedic Research Society Quality of Life of the European Foundation for Osteporosis Roland-Morris Disability Questionnaire standard deviation 36-Item Short Form Survey Instrument 36-Item Short Form Survey Instrument Mental Component Score 36-Item Short Form Survey Instrument Physical Component Score AAOS Clinical Practice Guidelines Unit sickness impact profile Study of Osteoporotic Fractures-Activities of Daily Living visual analog scale weighted mean difference AAOS Clinical Practice Guidelines Unit APPENDIX XII
CONFLICT OF INTEREST
All members of the AAOS work group disclosed any conflicts of interest prior to the development of the recommendations for this guideline. Conflicts of interest are disclosed in writing with the American Academy of Orthopaedic Surgeons via a private on-line reporting database and also verbally at the recommendation approval meeting. Stephen I Esses, MD (Houston, TX): 2 (Orthopedics; Spine; THE SPINE JOURNAL).
Submitted on: 10/23/2009 and last confirmed as accurate on 01/22/2010.
Joel A Finkelstein, MD (Toronto, ON Canada): 7 (Stryker; Synthes). Submitted on:
02/03/2009.
John Jenkins (Jackson, TN): 4 (Norvartis; Procter & Gamble; Roche). Submitted on:
03/11/2009.
Robert A McGuire, Jr MD (Jackson, MS): 1 (AOSpine North America chairman); 2
(Journal of Spinal Disorders); 3 (DePuy, A Johnson & Johnson Company); 5A (Synthes);
7 (AO; Stryker). Submitted on: 02/16/2009.
Eric John Woodard, MD (Boston, MA): 1 (AOSpine); 4 (DePuy, A Johnson & Johnson
Company; Stryker; Synthes); 5A (invivo therapeutics); 7 (Synthes; AOSpine); 8
(Medtronic); 10 (Nanoventures). Submitted on: 03/24/2009.
William Charles Watters III, MD (Houston, TX): 1 (North American Spine Society;
American Board of Spine Surgery; Board of Advisoer Official Disability Guidelines;
Associate Member of The Editorial Board, The Spine Journal; Med Center Ambulatory
Surgery Center); 2 (The Spine Journal); 4 (Stryker; Synthes); 5A (Orthofix, Inc.;
Stryker); 8 (Intrisic Therapeutics). Submitted on: 08/14/2009.

Disclosure Items: (n) = Respondent answered 'No' to all items indicating no conflicts.
1=Board member/owner/officer/committee appointments; 2= Medical/Orthopaedic
Publications; 3= Royalties; 4= Speakers bureau/paid presentations;5A= Paid consultant;
5B= Unpaid consultant; 6= Research or institutional support from a publisher; 7=
Research or institutional support from a company or supplier; 8= Stock or Stock Options;
9= Other financial/material support from a publisher; 10= Other financial/material
support from a company or supplier.
AAOS Clinical Practice Guidelines Unit APPENDIX XIII
REFERENCES
(1) Buchbinder R, Osborne RH, Ebeling PR et al. A randomized trial of vertebroplasty for painful osteoporotic vertebral fractures. N Engl J Med 2009;361(6):557-568. (2) American Academy of Orthopaedic Surgeons. The Burden of Musculoskeletal Diseases in the United States. American Academy of Orthopaedic Surgeons; 2008. (3) Cook D.J., Mulrow CD, Haynes RB. Systematic Reviews:synthesis of best evidence for clinical decisions. Ann Intern Med 1997;126(5):376-380. (4) Mulrow C.D., Cook D.J., Davidoff F. Systematic Reviews:critical links in the great chain of evidence. Ann Intern Med 1997;126(5):389-391. (5) Brookes ST, Whitely E, Egger M, Smith GD, Mulheran PA, Peters TJ. Subgroup analyses in randomized trials: risks of subgroup-specific analyses; power and sample size for the interaction test. J Clin Epidemiol 2004;57(3):229-236. (6) Bucher H.C., Guyatt G.H., Cook D.J., Holbrook A., McAlister F.A. Users' Guides to the Medical Literature. JAMA 1999;282(8). 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The effects of strontium ranelate on the risk of vertebral fracture in women with postmenopausal osteoporosis. N Engl J Med 2004;350(5):459-468. (33) Brumsen C, Papapoulos SE, Lips P et al. Daily oral pamidronate in women and men with osteoporosis: a 3-year randomized placebo-controlled clinical trial with a 2-year open extension. J Bone Miner Res 2002;17(6):1057-1064. (34) Black DM, Cummings SR, Karpf DB et al. Randomised trial of effect of alendronate on risk of fracture in women with existing vertebral fractures. Fracture Intervention Trial Research Group. Lancet 1996;348(9041):1535-1541. (35) Chesnut CH, III, Silverman S, Andriano K et al. A randomized trial of nasal spray salmon calcitonin in postmenopausal women with established osteoporosis: the prevent recurrence of osteoporotic fractures study. PROOF Study Group. Am J Med 2000;109(4):267-276. (36) Gutteridge DH, Stewart GO, Prince RL et al. A randomized trial of sodium fluoride (60 mg) (plus or minus) estrogen in postmenopausal osteoporotic vertebral fractures: Increased vertebral fractures and peripheral bone loss with sodium fluoride; concurrent estrogen prevents peripheral loss, but not vertebral fractures. Osteoporosis International 2002;13(2):158-170. AAOS Clinical Practice Guidelines Unit (37) Lufkin EG, Wahner HW, O'Fallon WM et al. Treatment of postmenopausal osteoporosis with transdermal estrogen. Ann Intern Med 1992;117(1):1-9. (38) Wimalawansa SJ. A four-year randomized controlled trial of hormone replacement and bisphosphonate, alone or in combination, in women with postmenopausal osteoporosis. Am J Med 1998;104(3):219-226. (39) Watts NB, Harris ST, Genant HK et al. Intermittent cyclical etidronate treatment of postmenopausal osteoporosis. N Engl J Med 1990;323(2):73-79. (40) Pak CY, Sakhaee K, Piziak V et al. Slow-release sodium fluoride in the management of postmenopausal osteoporosis. A randomized controlled trial. Ann Intern Med 1994;120(8):625-632. (41) Meunier PJ, Sebert JL, Reginster JY et al. Fluoride salts are no better at preventing new vertebral fractures than calcium-vitamin D in postmenopausal osteoporosis: the FAVOStudy. Osteoporos Int 1998;8(1):4-12. (42) Ringe JD, Kipshoven C, Coster A, Umbach R. Therapy of established postmenopausal osteoporosis with monofluorophosphate plus calcium: dose-related effects on bone density and fracture rate. Osteoporos Int 1999;9(2):171-178. (43) Rubin CD, Pak CY, Adams-Huet B, Genant HK, Li J, Rao DS. Sustained-release sodium fluoride in the treatment of the elderly with established osteoporosis. Arch Intern Med 2001;161(19):2325-2333. (44) Maugeri D, Panebianco P, Russo MS et al. Ipriflavone-treatment of senile osteoporosis: results of a multicenter, double-blind clinical trial of 2 years. Arch Gerontol Geriatr 1994;19(3):253-263. (45) Inoue T, Fujita T, Kishimoto H et al. Randomized controlled study on the prevention of osteoporotic fractures (OF study): a phase IV clinical study of 15-mg menatetrenone capsules. J Bone Miner Metab 2009;27(1):66-75. (46) Matsumoto T, Hagino H, Shiraki M et al. Effect of daily oral minodronate on vertebral fractures in Japanese postmenopausal women with established osteoporosis: a randomized placebo-controlled double-blind study. Osteoporos Int 2008. (47) Lufkin EG, Whitaker MD, Nickelsen T et al. Treatment of established postmenopausal osteoporosis with raloxifene: a randomized trial. J Bone Miner Res 1998;13(11):1747-1754. (48) Ettinger B, Black DM, Mitlak BH et al. Reduction of vertebral fracture risk in postmenopausal women with osteoporosis treated with raloxifene: results from a 3-year randomized clinical trial. Multiple Outcomes of Raloxifene Evaluation (MORE) Investigators. JAMA 1999;282(7):637-645. AAOS Clinical Practice Guidelines Unit (49) Clemmesen B, Ravn P, Zegels B, Taquet AN, Christiansen C, Reginster JY. A 2- year phase II study with 1-year of follow-up of risedronate (NE-58095) in postmenopausal osteoporosis. Osteoporos Int 1997;7(5):488-495. (50) Harris ST, Watts NB, Genant HK et al. Effects of risedronate treatment on vertebral and nonvertebral fractures in women with postmenopausal osteoporosis: a randomized controlled trial. Vertebral Efficacy With Risedronate Therapy (VERT) Study Group. JAMA 1999;282(14):1344-1352. (51) Reginster J, Minne HW, Sorensen OH et al. Randomized trial of the effects of risedronate on vertebral fractures in women with established postmenopausal osteoporosis. Vertebral Efficacy with Risedronate Therapy (VERT) Study Group. Osteoporos Int 2000;11(1):83-91. (52) Meunier PJ, Slosman DO, Delmas PD et al. Strontium ranelate: dose-dependent effects in established postmenopausal vertebral osteoporosis--a 2-year randomized placebo controlled trial. J Clin Endocrinol Metab 2002;87(5):2060-2066. (53) Neer RM, Arnaud CD, Zanchetta JR et al. Effect of parathyroid hormone (1-34) on fractures and bone mineral density in postmenopausal women with osteoporosis. N Engl J Med 2001;344(19):1434-1441. (54) Wardlaw D, Cummings SR, Van MJ et al. Efficacy and safety of balloon kyphoplasty compared with non-surgical care for vertebral compression fracture (FREE): a randomised controlled trial. Lancet 2009;373(9668):1016-1024. (55) Rousing R, Andersen MO, Jespersen SM, Thomsen K, Lauritsen J. Percutaneous vertebroplasty compared to conservative treatment in patients with painful acute or subacute osteoporotic vertebral fractures: three-months follow-up in a clinical randomized study. Spine 2009;34(13):1349-1354. (56) Kushida K, Shiraki M, Nakamura T et al. The efficacy of alendronate in reducing the risk for vertebral fracture in Japanese patients with osteoporosis: A randomized, double-blind, active-controlled, double-dummy trial. Current Therapeutic Research - Clinical and Experimental 2002;63(9):606-620. (57) Gutteridge DH, Holzherr ML, Retallack RW et al. A randomized trial comparing hormone replacement therapy (HRT) and HRT plus calcitriol in the treatment of postmenopausal osteoporosis with vertebral fractures: benefit of the combination on total body and hip density. Calcif Tissue Int 2003;73(1):33-43. (58) Guanabens N, Farrerons J, Perez-Edo L et al. Cyclical etidronate versus sodium fluoride in established postmenopausal osteoporosis: a randomized 3 year trial. Bone 2000;27(1):123-128. (59) Kushida K, Fukunaga M, Kishimoto H et al. A comparison of incidences of vertebral fracture in Japanese patients with involutional osteoporosis treated with AAOS Clinical Practice Guidelines Unit risedronate and etidronate: a randomized, double-masked trial. J Bone Miner Metab 2004;22(5):469-478. (60) Grohs JG, Matzner M, Trieb K, Krepler P. Minimal invasive stabilization of osteoporotic vertebral fractures: a prospective nonrandomized comparison of vertebroplasty and balloon kyphoplasty. J Spinal Disord Tech 2005;18(3):238-242. (61) Liu JT, Liao WJ, Tan WC et al. Balloon kyphoplasty versus vertebroplasty for treatment of osteoporotic vertebral compression fracture: a prospective, comparative, and randomized clinical study. Osteoporos Int 2009. (62) Iwamoto J, Takeda T, Ichimura S, Uzawa M. Comparative effects of treatment with etidronate and alendronate on bone resorption, back pain, and activities of daily living in elderly women with vertebral fractures. Keio J Med 2003;52(4):230-235. (63) Gallagher JC, Goldgar D. Treatment of postmenopausal osteoporosis with high doses of synthetic calcitriol. A randomized controlled study. Ann Intern Med 1990;113(9):649-655. (64) Geusens P, Dequeker J. Long-term effect of nandrolone decanoate, 1 alpha- hydroxyvitamin D3 or intermittent calcium infusion therapy on bone mineral content, bone remodeling and fracture rate in symptomatic osteoporosis: a double-blind controlled study. Bone Miner 1986;1(4):347-357. (65) Hodsman AB, Fraher LJ, Watson PH et al. A randomized controlled trial to compare the efficacy of cyclical parathyroid hormone versus cyclical parathyroid hormone and sequential calcitonin to improve bone mass in postmenopausal women with osteoporosis. J Clin Endocrinol Metab 1997;82(2):620-628. (66) Ohtori S, Yamashita M, Inoue G et al. L2 Spinal Nerve-Block Effects on Acute Low Back Pain From Osteoporotic Vertebral Fracture. J Pain 2009;10(8):870-875. (67) Pfeifer M, Begerow B, Minne HW. Effects of a New Spinal Orthosis on Posture, Trunk Strength, and Quality of Life in Women with Postmenopausal Osteoporosis: A Randomized Trial. Am J Phys Med Rehabil 2004;83(3):177-186. (68) Papaioannou A, Adachi JD, Winegard K et al. Efficacy of home-based exercise for improving quality of life among elderly women with symptomatic osteoporosis-related vertebral fractures. Osteoporos Int 2003;14(8):677-682. (69) Rossini M, Viapiana O, Gatti D, De TF, Adami S. Capacitively Coupled Electric Field for Pain Relief in Patients with Vertebral Fractures and Chronic Pain. Clin Orthop Relat Res 2009. AAOS Clinical Practice Guidelines Unit (70) Kallmes DF, Comstock BA, Heagerty PJ et al. A randomized trial of vertebroplasty for osteoporotic spinal fractures. N Engl J Med 2009;361(6):569-579. (71) Voormolen MH, Mali WP, Lohle PN et al. Percutaneous vertebroplasty compared with optimal pain medication treatment: short-term clinical outcome of patients with subacute or chronic painful osteoporotic vertebral compression fractures. The VERTOS study. AJNR Am J Neuroradiol 2007;28(3):555-560. (72) Diamond TH, Bryant C, Browne L, Clark WA. Clinical outcomes after acute osteoporotic vertebral fractures: a 2-year non-randomised trial comparing percutaneous vertebroplasty with conservative therapy. Med J Aust 2006;184(3):113-117. (73) Grafe IA, Da FK, Hillmeier J et al. Reduction of pain and fracture incidence after kyphoplasty: 1-year outcomes of a prospective controlled trial of patients with primary osteoporosis. Osteoporos Int 2005;16(12):2005-2012. (74) De Negri P, Tirri T, Paternoster G, Modano P. Treatment of painful osteoporotic or traumatic vertebral compression fractures by percutaneous vertebral augmentation procedures: a nonrandomized comparison between vertebroplasty and kyphoplasty. Clin J Pain 2007;23(5):425-430. (75) Kasperk C, Hillmeier J, Noldge G et al. Treatment of painful vertebral fractures by kyphoplasty in patients with primary osteoporosis: a prospective nonrandomized controlled study. J Bone Miner Res 2005;20(4):604-612. (76) Petitti DB, Teutsch SM, Barton MB, Sawaya GF, Ockene JK, DeWitt T. Update on the methods of the U.S. Preventive Services Task Force: insufficient evidence. Ann Intern Med 2009;150(3):199-205. AAOS Clinical Practice Guidelines Unit
EXCLUDED ARTICLES AND REASON FOR EXCLUSION
Table 96 Excluded Articles and Reason for Exclusion
Author Title
Reason for Exclusion
Treating osteoporosis in Canada: What clinical efficacy data should be considered by policy decision Systematic review, bibliography Assessing compliance, acceptance, and tolerability of teriparatide in patients with osteoporosis who Does not investigate efficacy of fractured while on antiresorptive treatment or were intolerant to previous antiresorptive treatment: an 18-month, multicenter, open-label, prospective stu Vertebral fracture risk reduction with risedronate in post-menopausal women with osteoporosis: a Systematic review, bibliography meta-analysis of individual patient data Effect of raloxifene after recombinant teriparatide [hPTH(1-34)] treatment in postmenopausal women Incorrect patient population with osteoporosis Protelos: nonvertebral and hip antifracture efficacy in postmenopausal osteoporosis Not specific to fracture patients Alendronate for the treatment of osteoporosis in men Narrative review, bibliography screened Vertebroplasty and kyphoplasty for the treatment of vertebral compression fracture (Brief record) Systematic review, bibliography Percutaneous vertebroplasty for osteoporotic fractures Not best available evidence Efficacy of ipriflavone in established osteoporosis and long-term safety Narrative review, bibliography screened Effects of ipriflavone on bone mass and calcium metabolism in postmenopausal osteoporosis Not specific to fracture patients Short-segment pedicle instrumentation of thoracolumbar burst fractures: does transpedicular Incorrect patient population intracorporeal grafting prevent early failure? Alexandersen 2001 Ipriflavone in the treatment of postmenopausal osteoporosis: a randomized controlled trial Incorrect patient population Early parathyroidectomy increases bone mineral density in patients with mild primary Incorrect patient population hyperparathyroidism: a prospective and randomized study Percutaneous vertebroplasty: functional improvement in patients with osteoporotic compression Not best available evidence Predictors of outcomes of percutaneous vertebroplasty for osteoporotic vertebral fractures Retrospective case series Use of a screw-syringe injector for cement delivery during kyphoplasty: technical report Surgical Technique Percutaneous transpedicular polymethylmethacrylate vertebroplasty for the treatment of spinal Retrospective case series compression fractures Vertebroplasty in the treatment of spine disease Not best available evidence AAOS Clinical Practice Guidelines Unit Table 96 Excluded Articles and Reason for Exclusion
Author Title
Reason for Exclusion
Effect of intermittent cyclical disodium etidronate therapy on bone mineral density in men with Does not report patient oriented vertebral fractures Zoledronic acid improves bone density and reduces fractures Strontium: new drug. Postmenopausal osteoporosis: too many unknowns Narrative review, bibliography screened Teriparatide: new preparation. Osteoporosis: less well evaluated than alendronic acid Narrative review, bibliography screened Fluoride and bone: a second look. No use in osteoporosis Narrative review, bibliography screened Measuring quality of life in women with osteoporosis. Osteoporosis Quality of Life Study Group Does not investigate efficacy of treatment Percutaneous vertebroplasty and bone cement leakage: clinical experience with a new high-viscosity Does not compare two treatments; bone cement and delivery system for vertebral augmentation in benign and malignant compression compares techniques of a treatment Pain relief following percutaneous vertebroplasty: results of a series of 283 consecutive patients Not best available evidence treated in a single institution Treatment of painful compression vertebral fractures with vertebroplasty: results and complications Not best available evidence Postmenopausal bilateral oophorectomy is not associated with increased fracture risk in older women Does not investigate efficacy of treatment Vertebral fracture diagnosis in the multinational BONE study of oral ibandronate: quality Does not investigate efficacy of management in radiology Intravenous pamidronate for pain relief in recent osteoporotic vertebral compression fracture: a Treatment comparison not relevant randomized double-blind controlled study Percutaneous vertebroplasty in osteoporotic vertebral compression fractures: our initial experience Not best available evidence A Bayesian analysis of bisphosphonate effects and cost-effectiveness in post-menopausal osteoporosis Systematic review, bibliography screened Vitamin D and vitamin D analogues for preventing fractures associated with involutional and post- Systematic review, bibliography menopausal osteoporosis Z-plate instrumentation in thoracolumbar spinal fractures Incorrect patient population The pedicle screw fixation with vertebroplasty augmentation in the surgical treatment of the severe Not best available evidence osteoporotic spines AAOS Clinical Practice Guidelines Unit Table 96 Excluded Articles and Reason for Exclusion
Author Title
Reason for Exclusion
Comparison of thoracolumbosacral orthosis and no orthosis for the treatment of thoracolumbar burst Incorrect patient population, non- fractures: interim analysis of a multicenter randomized clinical equivalence trial osteoporotic patients Back stab: percutaneous vertebroplasty for severe back pain Systematic review, bibliography screened Quality of life in osteoporotic women with inadequate clinical response to antiresorptive drugs: results Insufficient data from the ICARO study Percutaneous vertebroplasty: the follow-up Not best available evidence Biomechanical impact of vertebroplasty. Postoperative biomechanics of vertebroplasty Narrative review, bibliography screened Vertebral augmentation in osteoporotic fractures Narrative review, bibliography screened Short-term changes in bone turnover markers and bone mineral density response to parathyroid Not specific to fracture patients hormone in postmenopausal women with osteoporosis Kyphoplasty and vertebroplasty for the treatment of osteoporotic vertebral compression fractures Narrative review, bibliography screened Is there an indication for prophylactic balloon kyphoplasty? A pilot study Does not compare two treatments; compares techniques of a treatment Kyphoplasty for treatment of osteoporotic vertebral fractures: a prospective non-randomized study Not best available evidence Cement leakage in percutaneous vertebroplasty: effect of preinjection gelfoam embolization Not best available evidence Bierschneider 2005 Minimally invasive vertebral augmentation techniques in osteoporotic fractures Narrative review, bibliography screened Six and twelve month changes in bone turnover are related to reduction in vertebral fracture risk Not specific to fracture patients during 3 years of raloxifene treatment in postmenopausal osteoporosis Once-yearly zoledronic acid for treatment of postmenopausal osteoporosis Not specific to fracture patients Fracture risk reduction with alendronate in women with osteoporosis: the Fracture Intervention Trial. Subgroup analysis of included RCT FIT Research Group The effect of alendronate therapy on osteoporotic fracture in the vertebral fracture arm of the Fracture Intervention Trial Design of the Fracture Intervention Trial Description of study design A review of strontium ranelate and its effect on DXA scans Narrative review, bibliography screened AAOS Clinical Practice Guidelines Unit Table 96 Excluded Articles and Reason for Exclusion
Author Title
Reason for Exclusion
Strontium ranelate: a novel treatment for postmenopausal osteoporosis: a review of safety and efficacy Narrative review, bibliography screened Suitability of a calcium phosphate cement in osteoporotic vertebral body fracture augmentation: a Does not compare two treatments; controlled, randomized, clinical trial of balloon kyphoplasty comparing calcium phosphate versus compares techniques of a treatment polymethylmethacrylate Analgesic efficacy of calcitonin for vertebral fracture pain Systematic review, bibliography screened Comparison of direct health care costs related to the pharmacological treatment of osteoporosis and to Cost-effectiveness study the management of osteoporotic fractures among compliant and noncompliant users of alendronate and risedronate: A population-based study Calcitonin for the long-term prevention and treatment of postmenopausal osteoporosis Narrative review, bibliography screened A randomized double-blind trial to compare the efficacy of teriparatide [recombinant human Not specific to fracture patients parathyroid hormone (1-34)] with alendronate in postmenopausal women with osteoporosis Patient satisfaction in postmenopausal women treated with a weekly bisphosphonate transitioned to Not specific to fracture patients once-monthly ibandronate Treatment with alendronate plus calcium, alendronate alone, or calcium alone for postmenopausal low Not specific to fracture patients bone mineral density Once-weekly risedronate in men with osteoporosis: Results of a 2-Year, placebo-controlled, double- Not specific to fracture patients blind, multicenter study Safety and efficacy of risedronate in reducing fracture risk in osteoporotic women aged 80 and older: Systematic review, bibliography implications for the use of antiresorptive agents in the old and oldest old Cost effectiveness of raloxifene in the treatment of osteoporosis in Sweden: an economic evaluation Cost-effectiveness study based on the MORE study Microsurgical interlaminary vertebro- and kyphoplasty for severe osteoporotic fractures Retrospective case series Teriparatide and raloxifene reduce the risk of new adjacent vertebral fractures in postmenopausal Narrative review, bibliography women with osteoporosis: Results from two randomized controlled trials Efficacy and safety of balloon kyphoplasty in the treatment of vertebral compression fractures: a Systematic review, bibliography systematic review Treatment of osteoporosis with parathyroid peptide (hPTH 1-34) and oestrogen: increase in Does not report patient oriented volumetric density of iliac cancellous bone may depend on reduced trabecular spacing as well as increased thickness of packets of newly formed bone Outcome of CT-guided vertebroplasty in outpatients with severe vertebral compression fractures Retrospective case series AAOS Clinical Practice Guidelines Unit Table 96 Excluded Articles and Reason for Exclusion
Author Title
Reason for Exclusion
Bone histomorphometric evaluation of pamidronate treatment in clinically manifest osteoporosis Does not report patient oriented outcomes Health-economic comparison of three recommended drugs for the treatment of osteoporosis Cost-effectiveness study How long should patients take medications for postmenopausal osteoporosis? Narrative review, bibliography screened Vertebral augmentation with a flexible curved needle: preliminary results in 17 consecutive patients Not best available evidence Gaps in Treatment Among Users of Osteoporosis Medications: The Dynamics of Noncompliance Does not investigate efficacy of treatment Correlation between preprocedural MRI findings and clinical outcomes in the treatment of chronic Retrospective case series symptomatic vertebral compression fractures with percutaneous vertebroplasty Treatment of chronic symptomatic vertebral compression fractures with percutaneous vertebroplasty Retrospective case series The efficacy and tolerability of risedronate once a week for the treatment of postmenopausal Not specific to fracture patients Effects of strontium ranelate on spinal osteoarthritis progression Incorrect patient population Effective inhibition of aromatase inhibitor-associated bone loss by zoledronic acid in postmenopausal Not specific to fracture patients women with early breast cancer receiving adjuvant letrozole: ZO-FAST study results The effect of treatment with calcitonin on vertebral fracture rate in osteoporosis Systematic review, bibliography screened Percutaneous sacroplasty for the treatment of sacral insufficiency fractures Less than 10 patients per group Five year study of etidronate and/or calcium as prevention and treatment for osteoporosis and Not specific to fracture patients fractures in patients with asthma receiving long term oral and/or inhaled glucocorticoids Pathogenesis of vertebral crush fractures in women Does not investigate efficacy of treatment Osteoporotic vertebral collapse: percutaneous vertebroplasty and local kyphosis correction Not best available evidence CT-guided percutaneous vertebroplasty: personal experience in the treatment of osteoporotic fractures Not best available evidence and dorsolumbar metastases Timing of thoracolomber spine stabilization in trauma patients; impact on neurological outcome and Incorrect patient population clinical course. A real prospective (rct) randomized controlled study Evidence based medicine and effective interventions of pharmacological therapy for the prevention of Systematic review, bibliography osteoporotic fractures Unipedicular vertebroplasty for osteoporotic compression fracture using an individualized needle Not best available evidence AAOS Clinical Practice Guidelines Unit Table 96 Excluded Articles and Reason for Exclusion
Author Title
Reason for Exclusion
Single annual injectable treatment for postmenopausal osteoporosis Narrative review, bibliography screened Outcomes of a disease-management program for patients with recent osteoporotic fracture Does not investigate efficacy of treatment Kyphoplasty for chronic painful osteoporotic vertebral compression fractures via unipedicular versus Not relevant, comparison not bipedicular approachment: A comparative study in early stage considered for this guideline Intracorporal bone grafting for vertebral compression fractures with intraosseous vacuum Not best available evidence Percutaneous vertebroplasty for the treatment of osteoporotic vertebral compression fractures Not best available evidence Percutaneous vertebroplasty for the treatment of osteoporotic vertebral compression fractures: a Not best available evidence preliminary report Ibandronate produces significant, similar antifracture efficacy in North American and European Duplicate study data, subgroup analysis women: new clinical findings from BONE Stanozolol in postmenopausal osteoporosis: therapeutic efficacy and possible mechanisms of action Insufficient data Vertebroplasty by use of a strontium-containing bioactive bone cement Narrative review, bibliography screened An osteoporosis clinical pathway for the medical management of patients with low-trauma fracture Incorrect patient population Vertebroplasty utilizing percutaneous vertebral body access (PVBA) technique for osteoporotic Retrospective case series vertebral compression fractures in the middle thoracic vertebrae Successful salvage using percutaneous vertebroplasty in cancer patients with painful spinal metastases Incorrect patient population or osteoporotic compression fractures Chrischilles 2001 The effect of alendronate on fracture-related healthcare utilization and costs: The fracture intervention Cost-effectiveness study Christodoulou 2005 Vertebral body reconstruction with injectable hydroxyapatite cement for the management of unstable Incorrect patient population thoracolumbar burst fractures: a preliminary report Comparative study of balloon kyphoplasty with unilateral versus bilateral approach in osteoporotic Does not compare two treatments; vertebral compression fractures compares techniques of a treatment Colon Emeric 2006 Osteoporotic fractures in older adults Narrative review, bibliography screened Equivalence of nasal spray and subcutaneous formulations of salmon calcitonin Does not compare two treatments; compares techniques of a treatment Comite d'Evaluation 2006 Kyphoplasty - systematic review, expert panel (Brief record) AAOS Clinical Practice Guidelines Unit Table 96 Excluded Articles and Reason for Exclusion
Author Title
Reason for Exclusion
Guidelines for the diagnosis and management of osteoporosis in postmenopausal women and men Guideline summary from the age of 50 years in the UK Prevention of vertebral fractures by strontium ranelate in postmenopausal women with osteoporosis Narrative review, bibliography screened Evaluation of spinal curvatures after a recent osteoporotic vertebral fracture Does not investigate efficacy of treatment Percutaneous vertebroplasty in the treatment of osteoporotic vertebral compression fractures: an open Not best available evidence prospective study Kyphoplasty for vertebral compression fractures: 1-year clinical outcomes from a prospective study Not best available evidence Cost effectiveness of nasal calcitonin in postmenopausal women: use of Cochrane Collaboration Systematic review, bibliography methods for meta-analysis within economic evaluation Association of severe vertebral fractures with reduced quality of life: reduction in the incidence of Post hoc subgroup analysis of included severe vertebral fractures by teriparatide Combined treatment of post-menopausal osteoporosis: effect on muscle function and a new Not best available evidence radiological method for assessing trabecular bone Denosumab for prevention of fractures in postmenopausal women with osteoporosis Not specific to fracture patients The effects of tibolone in older postmenopausal women Incorrect patient population Benefit of adherence with bisphosphonates depends on age and fracture type: Results from an analysis Not specific to fracture patients of 101,038 new bisphosphonate users Prevention and treatment of glucocorticoid-induced osteoporosis Narrative review, bibliography screened Acute osteoporotic vertebral collapse: open study on percutaneous injection of acrylic surgical cement Not best available evidence Double cement-application cavity containment kyphoplasty: technique description and efficacy Retrospective case series MRI findings after successful vertebroplasty Retrospective case series Dawson Hughes 2007 Response to teriparatide in patients with baseline 25-hydroxyvitamin D insufficiency or sufficiency Post hoc subgroup analysis Incremental cost of medical care after hip fracture and first vertebral fracture: The Rotterdam Study Does not investigate efficacy of treatment Combination teriparatide and raloxifene therapy for postmenopausal osteoporosis: results from a 6- Not specific to fracture patients month double-blind placebo-controlled trial Balloon kyphoplasty for vertebral compression fractures in solid organ transplant recipients: results of Not best available evidence treatment and comparison with primary osteoporotic vertebral compression fractures AAOS Clinical Practice Guidelines Unit Table 96 Excluded Articles and Reason for Exclusion
Author Title
Reason for Exclusion
Monthly dosing of 75 mg risedronate on 2 consecutive days a month: efficacy and safety results Not specific to fracture patients Efficacy and safety of risedronate 150 mg once a month in the treatment of postmenopausal Not specific to fracture patients Clinical effects of strontium ranelate in women with postmenopausal osteoporosis Narrative review, bibliography screened Severity of prevalent vertebral fractures and the risk of subsequent vertebral and nonvertebral Post hoc subgroup analysis fractures: results from the MORE trial Efficacy of raloxifene on vertebral fracture risk reduction in postmenopausal women with Subgroup analysis of included RCT osteoporosis: four-year results from a randomized clinical trial Treatment of vertebral osteoporosis with disodium monofluorophosphate: comparison with sodium Not best available evidence Nonpharmacological prevention of osteoporotic fractures Narrative review, bibliography screened Clinical outcomes after acute osteoporotic vertebral fractures: a 2-year non-randomised trial Not best available evidence comparing percutaneous vertebroplasty with conservative therapy Management of acute osteoporotic vertebral fractures: a nonrandomized trial comparing percutaneous Interim Analysis vertebroplasty with conservative therapy Guidelines for treatment of osteoporosis in men Systematic review, bibliography screened Vertebroplasty and kyphoplasty: rapid pain relief for vertebral compression fractures Narrative review, bibliography screened Prospective analysis of clinical outcomes after percutaneous vertebroplasty for painful osteoporotic Not best available evidence vertebral body fractures Percutaneous vertebroplasty: rationale, clinical outcomes, and future directions Narrative review, bibliography screened New horizons for zoledronic acid: Results of the HORIZON trials in postmenopausal women with osteoporosis and after hip fracture Multiple adjacent vertebral fractures after kyphoplasty in a patient with steroid-induced osteoporosis Clinical relevance of pain patterns in osteoporotic vertebral compression fractures Not best available evidence Prevention of postmenopausal osteoporosis with oestrogen replacement therapy and associated Systematic review, bibliography compounds: update on clinical trials since 1995 An open-label extension study of alendronate treatment in elderly women with osteoporosis Not specific to fracture patients AAOS Clinical Practice Guidelines Unit Table 96 Excluded Articles and Reason for Exclusion
Author Title
Reason for Exclusion
Anabolic agents to treat osteoporosis in older people: is there still place for fluoride? Fluoride for Systematic review, bibliography treating postmenopausal osteoporosis Pulmonary cement embolism: a complication of percutaneous vertebroplasty Retrospective case series Fluoride therapy for osteoporosis: a review of dose response, duration of treatment, and skeletal sites Narrative review, bibliography Cost-effectiveness of bisphosphonate therapies for women with postmenopausal osteoporosis: Cost-effectiveness study implications of improved persistence with less frequently administered oral bisphosphonates Effect of once-yearly zoledronic acid five milligrams on fracture risk and change in femoral neck bone Post hoc subgroup analysis Sequential treatment of severe postmenopausal osteoporosis after teriparatide: final results of the Not relevant, sequential treatment not randomized, controlled european study of forsteo (EUROFORS) considered for this guideline Comparison of vertebroplasty and balloon kyphoplasty for treatment of vertebral compression Systematic review, bibliography fractures: a meta-analysis of the literature Vertebroplasty: a new treatment strategy for osteoporotic compression fractures Surgical Technique Percutaneous vertebroplasty: a review for the primary care physician Effects of raloxifene on fracture risk in postmenopausal women: the Raloxifene Use for the Heart Incorrect patient population Prevalent vertebral deformities predict mortality and hospitalization in older women with low bone Does not investigate efficacy of Alendronate reduced new fractures in postmenopausal women who had low bone-mineral density and existing vertebral fractures Correlates of kyphosis in older women. The Fracture Intervention Trial Research Group Does not investigate efficacy of treatment Treatment with alendronate prevents fractures in women at highest risk: results from the Fracture subgroup analysis of included RCT Intervention Trial Update on monthly oral bisphosphonate therapy for the treatment of osteoporosis: focus on Systematic review, bibliography ibandronate 150 mg and risedronate 150 mg The problem of low levels of vitamin D and osteoporosis: use of combination therapy with alendronic Narrative review, bibliography acid and colecalciferol (vitamin D3) Postmenopausal osteoporosis: fracture consequences and treatment efficacy vary by skeletal site Narrative review, bibliography screened AAOS Clinical Practice Guidelines Unit Table 96 Excluded Articles and Reason for Exclusion
Author Title
Reason for Exclusion
Teriparatide: A bone formation treatment for osteoporosis Narrative review, bibliography screened Simple computer model for calculating and reporting 5-year osteoporotic fracture risk in Does not investigate efficacy of postmenopausal women Vertebral compression fractures: pain reduction and improvement in functional mobility after Retrospective case series percutaneous polymethylmethacrylate vertebroplasty retrospective report of 245 cases Eyheremendy 2004 Percutaneous pediculoplasty in osteoporotic compression fractures Less than 10 patients per group Combining bisphosphonates with hormone therapy for postmenopausal osteoporosis Narrative review, bibliography screened The use of cyclical etidronate in osteoporosis: changes after completion of 3 years treatment Does not report patient oriented outcomes Postmenopausal osteoporosis: no effect of three years treatment with 1,25-dihydroxycholecalciferol Incorrect patient population Spinal fractures during fluoride therapy for osteoporosis: relationship to spinal bone density Retrospective case series Efficacy of long-term fluoride and calcium therapy in correcting the deficit of spinal bone density in Not best available evidence Sodium fluoride treatment is a major protector against vertebral and nonvertebral fractures when Not best available evidence compared with other common treatments of osteoporosis: a longitudinal, observational study Bone mineral density measurement and treatment for osteoporosis in older individuals with fractures: Does not investigate efficacy of A gap in evidence-based practice guideline implementation Oral ibandronate significantly reduces the risk of vertebral fractures of greater severity after 1, 2, and Post hoc subgroup analysis 3 years in postmenopausal women with osteoporosis Effects of Short-Term Risedronate on Bone Resorption and Patient Satisfaction in Postmenopausal Not specific to fracture patients Osteoporosis Patients Validation of a minimum outcome core set in the evaluation of patients with back pain Does not investigate efficacy of treatment Percutaneous vertebroplasty: a comparison between the procedure using the traditional and the new Not relevant, comparison not side-opening cannula for osteoporotic vertebral fracture considered for this guideline Osteoporosis risk factors in rural and urban women from the Lublin Region of Poland Does not investigate efficacy of treatment Cyclical intravenous clodronate in postmenopausal osteoporosis: results of a long-term clinical trial Not specific to fracture patients Finkelstein 2004 Diagnosis and management of pathological fractures of the spine Narrative review, bibliography screened AAOS Clinical Practice Guidelines Unit Table 96 Excluded Articles and Reason for Exclusion
Author Title
Reason for Exclusion
Percutaneous vertebroplasty: a bone cement procedure for spinal pain relief Narrative review, bibliography screened The cost effectiveness of bisphosphonates for the prevention and treatment of osteoporosis: a Cost-effectiveness study structured review of the literature Nandrolone decanoate and intranasal calcitonin as therapy in established osteoporosis Does not report relevant outcome Vesselplasty: a new technical approach to treat symptomatic vertebral compression fractures Not best available evidence Parathyroid hormone(1-84) treatment of postmenopausal women with low bone mass receiving Not specific to fracture patients hormone replacement therapy Thoracic and lumbar spine fusion: postoperative radiologic evaluation Retrospective case series Risedronate on two consecutive days per month Narrative review, bibliography screened Back pain in osteoporotic vertebral fractures Narrative review, bibliography screened Acute and long-term management of patients with vertebral fractures Systematic review, bibliography screened Androgen replacement in aging men Incorrect patient population A comparison of the effects of alfacalcidol treatment and vitamin D2 supplementation on calcium Does not report patient oriented absorption in elderly women with vertebral fractures Interdisciplinary approach to balloon kyphoplasty in the treatment of osteoporotic vertebral Narrative review, bibliography compression fractures Percutaneous vertebral augmentation: an elevation in adjacent-level fracture risk in kyphoplasty as Not best available evidence compared with vertebroplasty Percutaneous sacroplasty for osteoporotic sacral insufficiency fractures: a prospective, multicenter, Incorrect patient population observational pilot study Efficacy and safety of percutaneous sacroplasty for painful osteoporotic sacral insufficiency fractures: Incorrect patient population a prospective, multicenter trial Incidence of subsequent vertebral fracture after kyphoplasty Retrospective case series Clinical effect of bisphosphonate and vitamin D on osteoporosis: reappraisal of a multicenter double- Post hoc subgroup analysis blind clinical trial comparing etidronate and alfacalcidol Reappraisal of Katsuragi calcium study, a prospective, double-blind, placebo-controlled study of the Not specific to fracture patients effect of active absorbable algal calcium (AAACa) on vertebral deformity and fracture AAOS Clinical Practice Guidelines Unit Table 96 Excluded Articles and Reason for Exclusion
Author Title
Reason for Exclusion
A comparison of the effect of risedronate and etidronate on lumbar bone mineral density in Japanese Not specific to fracture patients patients with osteoporosis: a randomized controlled trial Percutaneous internal fixation of thoracolumbar spine fractures Less than 50% follow-up Teriparatide reduces the fracture risk associated with increasing number and severity of osteoporotic Post hoc subgroup analysis of included Analgesic effect of intravenous pamidronate on chronic back pain due to osteoporotic vertebral Retrospective case series Thoracic and lumbar spine fractures Narrative review, bibliography screened Prevention and treatment of osteoporotic fractures Narrative review, bibliography screened Balloon kyphoplasty for symptomatic vertebral body compression fractures results in rapid, Not best available evidence significant, and sustained improvements in back pain, function, and quality of life for elderly patients New technologies in spine: kyphoplasty and vertebroplasty for the treatment of painful osteoporotic Narrative review, bibliography compression fractures Lack of preoperative spinous process tenderness does not affect clinical success of percutaneous Retrospective case series Relevance of antecedent venography in percutaneous vertebroplasty for the treatment of osteoporotic Does not compare two treatments; compression fractures compares techniques of a treatment Reduction in vertebral fracture risk in teriparatide-treated postmenopausal women as assessed by Post hoc subgroup analysis of included spinal deformity index Analgesic effect of calcitonin in osteoporosis Narrative review, bibliography screened Combination kyphoplasty and spinal radiosurgery: a new treatment paradigm for pathological Incorrect patient population Scoliosis Research Society. Multicenter spine fracture study Incorrect patient population Review of risedronate in the treatment of osteoporosis Narrative review, bibliography screened Cyclical etidronate increases bone density in the spine and hip of postmenopausal women receiving Incorrect patient population long term corticosteroid treatment. A double blind, randomised placebo controlled study Bone mineral content, cortical thickness and fracture rate in osteoporotic women after withdrawal of Less than 10 patients per group treatment with nandrolone decanoate, 1-alpha hydroxyvitamin D3, or intermittent calcium infusions AAOS Clinical Practice Guidelines Unit Table 96 Excluded Articles and Reason for Exclusion
Author Title
Reason for Exclusion
Comparing pain reduction following kyphoplasty and vertebroplasty for osteoporotic vertebral Systematic review, bibliography compression fractures Advances in surgical treatment of osteoporotic fractures of the spine Narrative review, bibliography screened Do estrogen or selective estrogen receptor modulators improve quality of life for women with Narrative review, bibliography postmenopausal osteoporosis? Long-term observations of vertebral osteoporotic fractures treated by percutaneous vertebroplasty Retrospective case series Calcium-phosphate and polymethylmethacrylate cement in long-term outcome after kyphoplasty of Does not compare two treatments; painful osteoporotic vertebral fractures compares techniques of a treatment Reduction of pain and fracture incidence after kyphoplasty: 1-year outcomes of a prospective Not best available evidence controlled trial of patients with primary osteoporosis INvestigational Vertebroplasty Efficacy and Safety Trial (INVEST): a randomized controlled trial of Description of study design percutaneous vertebroplasty Alendronate improves bone mineral density in elderly women with osteoporosis residing in long-term Not specific to fracture patients care facilities: A randomized, double-blind, placebo-controlled trial Minimal invasive stabilization of osteoporotic vertebral fractures: a prospective nonrandomized Not best available evidence comparison of vertebroplasty and balloon kyphoplasty Postural taping decreases thoracic kyphosis but does not influence trunk muscle electromyographic Does not report patient oriented activity or balance in women with osteoporosis Relief of osteoporotic backache with fluoride, calcium, and calciferol Does not report recurrent and/or adjacent fractures Management of vertebral re-fractures after vertebroplasty in osteoporotic patients Not best available evidence Management of osteoporosis in women aged 50 and older with osteoporosis-related fractures in a Does not investigate efficacy of managed care population Percutaneous vertebroplasty for vertebral compression fractures with and without intravertebral clefts Not best available evidence Vertebral fractures: a hidden problem of osteoporosis Narrative review, bibliography screened Hadjipavlou 2005 Percutaneous vertebroplasty and balloon kyphoplasty for the treatment of osteoporotic vertebral Systematic review, bibliography compression fractures and osteolytic tumours A double-blinded head-to-head trial of minodronate and alendronate in women with postmenopausal Not specific to fracture patients AAOS Clinical Practice Guidelines Unit Table 96 Excluded Articles and Reason for Exclusion
Author Title
Reason for Exclusion
Etridronate therapy in the treatment and prevention of osteoporosis Narrative review, bibliography screened Kyphoplasty. A treatment for osteoporotic vertebral compression fractures Narrative review, bibliography screened Osteoporosis disease management for fragility fracture patients: New understandings based on three Does not investigate efficacy of years' experience with an osteoporosis care service Bisphosphonates for the treatment of postmenopausal osteoporosis: clinical studies of etidronate and Narrative review, bibliography Four-year study of intermittent cyclic etidronate treatment of postmenopausal osteoporosis: three Follow-up study to included RCT years of blinded therapy followed by one year of open therapy Primary and secondary osteoporosis' incidence of subsequent vertebral compression fractures after Retrospective case series Percutaneous treatment of osteoporotic spinal compression fractures Safety of osteoporosis treatment with sodium fluoride, calcium phosphate and vitamin D Not best available evidence Changes in soft tissue body composition and plasma lipid metabolism during nandrolone decanoate Does not report relevant outcome therapy in postmenopausal osteoporotic women Vertebroplasty and kyphoplasty: new treatments for painful osteoporotic vertebral fractures Narrative review, bibliography screened Risedronate reduces the risk of first vertebral fracture in osteoporotic women Incorrect patient population Intravenous pamidronate compared with oral alendronate for the treatment of postmenopausal Insufficient data Percutaneous transpedicular vertebroplasty with PMMA: operative technique and early results. A Not best available evidence prospective study for the treatment of osteoporotic compression fractures Minimally invasive reduction and internal stabilization of osteoporotic vertebral body fractures Not best available evidence (Balloon Kyphoplasty) Bone mineral density and bone markers in patients with a recent low-energy fracture: effect of 1 y of Incorrect patient population treatment with calcium and vitamin D Vertebroplasty for osteoporotic fractures with spinal canal compromise Retrospective case series Patients with osteoporosis on steroid medication tend to sustain subsequent fractures Retrospective case series Increase in vertebral body height after vertebroplasty Does not report patient oriented outcomes AAOS Clinical Practice Guidelines Unit Table 96 Excluded Articles and Reason for Exclusion
Author Title
Reason for Exclusion
Effects of alendronate on bone density in men with primary and secondary osteoporosis Does not report patient oriented outcomes Preventing fractures in postmenopausal women with osteoporosis. A review of recent controlled trials Systematic review, bibliography of antiresorptive agents Percutaneous vertebroplasty in the therapy of osteoporotic vertebral compression fractures: a critical Narrative review, bibliography Effects of cyclical therapy for osteoporosis using an oral regimen of inorganic phosphate and sodium Not best available evidence etidronate: a clinical and bone histomorphometric study PTH (1-34): a novel anabolic drug for the treatment of osteoporosis Narrative review, bibliography screened Hollingworth 2006 Evidence on the effectiveness and cost-effectiveness of vertebroplasty: A review of policy makers' Narrative review, bibliography Calcium absorption in postmenopausal osteoporosis: benefit of HRT plus calcitriol, but not HRT Does not report patient oriented alone, in both malabsorbers and normal absorbers Effect of low-intensity back exercise on quality of life and back extensor strength in patients with Not specific to fracture patients osteoporosis: a randomized controlled trial Pain relief in patients treated with percutaneous vertebroplasty: An evaluation cement volume Not best available evidence Complications of vertebroplasty and kyphoplasty Narrative review, bibliography screened Burst-fractures and cementoplasty Incorrect patient population Vertebroplasty and kyphoplasty: a systematic review of 69 clinical studies Systematic review, bibliography screened Complications related to vertebroplasty and kyphoplasty Narrative review, bibliography screened Institute for Clinical Vertebroplasty and balloon-assisted vertebroplasty for the treatment of osteoporotic compression Systematic review, bibliography Systems Improvement 2004 fractures (Structured abstract) Comparative efficacy of hormone replacement therapy, etidronate, calcitonin, alfacalcidol, and Not specific to fracture patients vitamin K in postmenopausal women with osteoporosis: The Yamaguchi Osteoporosis Prevention Study Risk factors for vertebral deformities in men: relationship to number of vertebral deformities. Does not investigate efficacy of European Vertebral Osteoporosis Study Group Effects of antifracture drugs in postmenopausal, male and glucocorticoid-induced osteoporosis-- Review of systematic reviews usefulness of alendronate and risedronate AAOS Clinical Practice Guidelines Unit Table 96 Excluded Articles and Reason for Exclusion
Author Title
Reason for Exclusion
Comparison of effect of treatment with etidronate and alendronate on lumbar bone mineral density in Insufficient data elderly women with osteoporosis Effects of alendronate on metacarpal and lumbar bone mineral density, bone resorption, and chronic Not best available evidence back pain in postmenopausal women with osteoporosis Determinants of one-year response of lumbar bone mineral density to alendronate treatment in elderly Not specific to fracture patients Japanese women with osteoporosis Effects of 5-year treatment with elcatonin and alfacalcidol on lumbar bone mineral density and the Not specific to fracture patients incidence of vertebral fractures in postmenopausal women with osteoporosis: a retrospective study Effect of menatetrenone on bone mineral density and incidence of vertebral fractures in Not specific to fracture patients postmenopausal women with osteoporosis: a comparison with the effect of etidronate Association Between Vertebral Fracture and Increased Mortality in Osteoporotic Patients Does not investigate efficacy of treatment Prevention of vertebral fractures in osteoporosis: mixed treatment comparison of bisphosphonate Systematic review, bibliography Treatment of osteoporosis in old age Narrative review, bibliography screened Position statement on percutaneous vertebral augmentation: a consensus statement developed by the Consensus statement American Society of Interventional and Therapeutic Neuroradiology, Society of Interventional Radiology, American Association of Neurological Surgeons/Congres Treatment of postmenopausal osteoporosis: is the anabolic steroid nandrolone decanoate a candidate? Does not report patient oriented outcomes Community-based population study of vertebral fractures in 85-year-old men and women Does not investigate efficacy of treatment Cost effectiveness of alendronate (fosamax) for the treatment of osteoporosis and prevention of Cost-effectiveness study Leakage of polymethylmethacrylate in percutaneous vertebroplasty: comparison of osteoporotic Not best available evidence vertebral compression fractures with and without an intravertebral vacuum cleft Cement augmentation of osteoporotic compression fractures and intraoperative navigation: summary Bazedoxifene reduces vertebral and clinical fractures in postmenopausal women at high risk assessed Not specific to fracture patients with FRAX((registered trademark)) Risedronate decreases fracture risk in patients selected solely on the basis of prior vertebral fracture Post hoc subgroup analysis Cost-effectiveness of raloxifene in the UK: an economic evaluation based on the MORE study Cost-effectiveness study AAOS Clinical Practice Guidelines Unit Table 96 Excluded Articles and Reason for Exclusion
Author Title
Reason for Exclusion
Effect of raloxifene on the risk of new vertebral fracture in postmenopausal women with osteopenia or Not specific to fracture patients osteoporosis: a reanalysis of the Multiple Outcomes of Raloxifene Evaluation trial Treatment of osteoporosis with vitamin D Narrative review, bibliography screened A double blind study of intranasal calcitonin for established postmenopausal osteoporosis Does not report patient oriented outcomes The cluster phenomenon in patients who have multiple vertebral compression fractures Does not investigate efficacy of treatment Posture training support: Preliminary report on a series of patients with diminished symptomatic Not best available evidence complications of osteoporosis Kapuscinski 1996 An analgesic effect of synthetic human calcitonin in patients with primary osteoporosis Not best available evidence Vertebroplasty and kyphoplasty: New treatment strategies for fractures in the osteoporotic spine Narrative review, bibliography screened Comparison of CT characteristics of extravertebral cement leakages after vertebroplasty performed by Does not compare two treatments; different navigation and injection techniques compares techniques of a treatment Treatment of painful vertebral fractures by kyphoplasty in patients with primary osteoporosis: a Not best available evidence prospective nonrandomized controlled study Teriparatide effects on vertebral fractures and bone mineral density in men with osteoporosis: Post hoc subgroup analysis treatment and discontinuation of therapy Age of fracture and clinical outcomes of percutaneous vertebroplasty Retrospective case series Percutaneous vertebroplasty for vertebral compression fracture: Indication, technique, and review of Retrospective case series Percutaneous vertebral compression fracture management with polyethylene mesh-contained Systematic review, bibliography morcelized allograft bone Functional outcomes of kyphoplasty for the treatment of osteoporotic and osteolytic vertebral Not best available evidence compression fractures Pulmonary cement embolism after percutaneous vertebroplasty in osteoporotic vertebral compression Not best available evidence fractures: incidence, characteristics, and risk factors Radiofrequency neurotomy of the gray ramus communicans for lumbar osteoporotic compression Retrospective case series Osteoporotic compression fractures of the spine; current options and considerations for treatment Narrative review, bibliography screened AAOS Clinical Practice Guidelines Unit Table 96 Excluded Articles and Reason for Exclusion
Author Title
Reason for Exclusion
Percutaneous vertebroplasty and facet joint block Not best available evidence Intravertebral vacuum phenomenon in osteoporotic compression fracture: report of 67 cases with Retrospective case series quantitative evaluation of intravertebral instability Risk factors of new compression fractures in adjacent vertebrae after percutaneous vertebroplasty Retrospective case series Nerve-root injections for the relief of pain in patients with osteoporotic vertebral fractures Not best available evidence VERTOS II: Percutaneous vertebroplasty versus conservative therapy in patients with painful Description of study design osteoporotic vertebral compression fractures; rationale, objectives and design of a multicenter randomized controlled trial Clinical outcomes with hemivertebral filling during percutaneous vertebroplasty Does not compare two treatments; compares techniques of a treatment Fate of the transpedicular intervertebral bone graft after posterior stabilisation of thoracolumbar Retrospective case series Calcitonin for treating acute pain of osteoporotic vertebral compression fractures: a systematic review Systematic review, bibliography of randomized, controlled trials Prophylactic vertebroplasty: cement injection into non-fractured vertebral bodies during percutaneous Does not compare two treatments; compares techniques of a treatment Percutaneous vertebroplasty immediately relieves pain of osteoporotic vertebral compression fractures Not best available evidence and prevents prolonged immobilization of patients Outcomes of patients receiving long-term corticosteroid therapy who undergo percutaneous Retrospective case series Percutaneous vertebroplasty for compression fracture: analysis of vertebral body volume by CT Not best available evidence Minimal invasive short posterior instrumentation plus balloon kyphoplasty with calcium phosphate for Not best available evidence burst and severe compression lumbar fractures Direct reduction of thoracolumbar burst fractures by means of balloon kyphoplasty with calcium Incorrect patient population phosphate and stabilization with pedicle-screw instrumentation and fusion Evolution of bone mineral density after percutaneous kyphoplasty in fresh osteoporotic vertebral body Not best available evidence fractures and adjacent vertebrae along with sagittal spine alignment Kyphosis reduction and the rate of cement leaks after vertebroplasty of intravertebral clefts Not best available evidence Management of pulmonary cement embolism after percutaneous vertebroplasty and kyphoplasty: a Systematic review, bibliography systematic review of the literature Bone mineral density and serum levels of 25 OH vitamin D in chronic users of antiepileptic drugs Incorrect patient population AAOS Clinical Practice Guidelines Unit Table 96 Excluded Articles and Reason for Exclusion
Author Title
Reason for Exclusion
Vertebroplasty in osteoporotic spine fractures: a quality of life assessment Not best available evidence Treatment of post-menopausal osteoporosis with phosphate and intermittent calcitonin Does not report patient oriented outcomes Alendronate reduced vertebral fracture risk in postmenopausal Japanese women with osteoporosis: a Less than 50% follow-up 3-year follow-up study Landin Wilhelmsen 2003 Growth hormone increases bone mineral content in postmenopausal osteoporosis: a randomized Not specific to fracture patients placebo-controlled trial Skeletal metabolism in patients with osteoporosis after discontinuation of long-term treatment with Not best available evidence oral pamidronate Intravertebral clefts opacified during vertebroplasty: pathogenesis, technical implications, and Retrospective case series prognostic significance Teriparatide versus alendronate for treating glucocorticoid-induced osteoporosis: an analysis by Not specific to fracture patients gender and menopausal status Effectiveness of antiresorptives for the prevention of nonvertebral low-trauma fractures in a Not specific to fracture patients population-based cohort of women Complications of percutaneous vertebroplasty and their prevention Narrative review, bibliography screened Comparison of the analgesic efficacy of pamidronate and synthetic human calcitonin in osteoporotic Treatment comparison not relevant vertebral fractures: a double-blind controlled study Use of injectable calcium phosphate cement for fracture fixation: a review Narrative review, bibliography screened Effect of s-calcitonin on pain related to recent osteoporotic vertebral fractures: A single-blind Treatment comparison not relevant controlled clinical study against ipriflavone Vertebroplasty and kyphoplasty Narrative review, bibliography screened Vertebroplasty and kyphoplasty Narrative review, bibliography screened Vertebroplasty, first 1000 levels of a single center: evaluation of the outcomes and complications Retrospective case series Vertebroplasty using real-time, fluoroscopy-controlled, catheter-assisted, low-viscosity cement Not best available evidence Clinical and radiographic results of unilateral transpedicular balloon kyphoplasty for the treatment of Not best available evidence osteoporotic vertebral compression fractures AAOS Clinical Practice Guidelines Unit Table 96 Excluded Articles and Reason for Exclusion
Author Title
Reason for Exclusion
Vertebroplasty and kyphoplasty for vertebral compression fractures Narrative review, bibliography screened The osteoporotic spine Does not investigate efficacy of treatment Legroux Gerot 2004 Long-term follow-up of vertebral osteoporotic fractures treated by percutaneous vertebroplasty Not best available evidence Leidig Bruckner 1994 Comparison of a semiquantitative and a quantitative method for assessing vertebral fractures in Does not investigate efficacy of The efficacy and tolerability of risedronate on bone mineral density and bone turnover markers in Not specific to fracture patients osteoporotic Chinese women: a randomized placebo-controlled study Pharmacologic and nonpharmacologic management of osteoporosis Narrative review, bibliography screened An evidence-based evaluation of percutaneous vertebroplasty Systematic review, bibliography screened Alendronate reduces the risk of multiple symptomatic fractures: results from the fracture intervention Subgroup analysis of included RCT Bazedoxifene and bazedoxifene combined with conjugated estrogens for the management of postmenopausal osteoporosis Effects of Knight-Taylor brace on balance performance in osteoporotic patients with vertebral Does not report patient oriented compression fracture Effect of oral alendronate on bone mineral density and the incidence of fractures in postmenopausal Not specific to fracture patients Surgical innovations: Kyphoplasty for women with compression fractures Narrative review, bibliography screened Vertebral augmentation and the limits of interpreting complications reported in the food and drug administration manufacturer and user facility device experience database Initial outcome and efficacy of 'kyphoplasty' in the treatment of painful osteoporotic vertebral Not best available evidence compression fractures Fractures of the thoraco-lumbar spine Incorrect patient population Percutaneous vertebroplasty improves pain and physical functioning in elderly osteoporotic vertebral Not best available evidence compression fracture patients New symptomatic compression fracture after percutaneous vertebroplasty at the thoracolumbar Retrospective case series AAOS Clinical Practice Guidelines Unit Table 96 Excluded Articles and Reason for Exclusion
Author Title
Reason for Exclusion
Vertebroplasty: cement leakage into the disc increases the risk of new fracture of adjacent vertebral Retrospective case series The role of imaging studies of percutaneous vertebroplasty in 63 patients with osteoporotic Not best available evidence compression fracture: Preliminary report Transpedicula PMMA vertebroplasty for the treatment of osteoporotic vertebral compression fracture Not best available evidence Interim report on treatment of osteoporotic patients with 1 alpha-hydroxyvitamin D3 and calcium Not best available evidence Longitudinal progression of fracture prevalence through a population of postmenopausal women with Does not investigate efficacy of Sustained vertebral fracture risk reduction after withdrawal of teriparatide in postmenopausal women Not best available evidence with osteoporosis Risk of new vertebral fracture in the year following a fracture Does not investigate efficacy of treatment Addition of alendronate to ongoing hormone replacement therapy in the treatment of osteoporosis: a Not specific to fracture patients randomized, controlled clinical trial Randomised controlled study of effect of parathyroid hormone on vertebral-bone mass and fracture Insufficient data incidence among postmenopausal women on oestrogen with osteoporosis Medical treatment of vertebral osteoporosis Systematic review, bibliography screened Effects of raloxifene hydrochloride on bone mineral density, bone metabolism and serum lipids in Not specific to fracture patients Chinese postmenopausal women with osteoporosis: a multi-center, randomized, placebo-controlled clinical trial Vertebroplasty and kyphoplasty: Complementary techniques for the treatment of painful osteoporotic Not best available evidence vertebral compression fractures. A prospective non-randomised study on 154 patients Vertebral fractures in steroid dependent asthma and involutional osteoporosis: a comparative study Does not investigate efficacy of treatment Economic evaluation of parathyroid hormone (PTH) in the treatment of osteoporosis in Cost-effectiveness study postmenopausal women Analgesic effects of calcitonin Narrative review, bibliography screened Gadolinium-enhanced magnetic resonance imaging after percutaneous vertebroplasty does not Not best available evidence improve the short-term prediction of new compression fractures Prospective study of standalone balloon kyphoplasty with calcium phosphate cement augmentation in Not best available evidence traumatic fractures AAOS Clinical Practice Guidelines Unit Table 96 Excluded Articles and Reason for Exclusion
Author Title
Reason for Exclusion
Preliminary outcomes and efficacy of the first 360 consecutive kyphoplasties for the treatment of Retrospective case series painful osteoporotic vertebral compression fractures Effects of risedronate or alfacalcidol on bone mineral density, bone turnover, back pain, and fractures Not specific to fracture patients in Japanese men with primary osteoporosis: results of a two-year strict observational study Efficacy of combined treatment with raloxifene and alfacalcidol on bone density and biochemical Not specific to fracture patients markers of bone turnover in postmenopausal osteoporosis Association between baseline values of bone turnover markers and bone mineral density and their Not specific to fracture patients response to raloxifene treatment in Japanese postmenopausal women with osteoporosis Clinical significance of 1-year treatment with raloxifene on bone and lipid metabolism in Japanese Not specific to fracture patients postmenopausal women with osteoporosis Incidental vertebral fractures discovered with chest radiography in the emergency department: Does not investigate efficacy of prevalence, recognition, and osteoporosis management in a cohort of elderly patients Maksymowych 1998 Managing acute osteoporotic vertebral fractures with calcitonin Systematic review, bibliography screened Positive effects of physiotherapy on chronic pain and performance in osteoporosis Insufficient data Risk-benefit ratio of sodium fluoride treatment in primary vertebral osteoporosis Insufficient data Minimally invasive techniques for the treatment of osteoporotic vertebral fractures Narrative review, bibliography screened Minimally invasive techniques for the treatment of osteoporotic vertebral fractures Narrative review, bibliography screened The teriparatide in the treatment of severe senile osteoporosis Does not report relevant outcome Effect of carbonated hydroxyapatite cement for filing vertebral body on the vertebral heights and pain Does not compare two treatments; in patients with osteoporotic vertebral compression fractures compares techniques of a treatment The skeletal response to teriparatide is largely independent of age, initial bone mineral density, and Post hoc subgroup analysis of included prevalent vertebral fractures in postmenopausal women with osteoporosis Antiresorptive treatment of postmenopausal osteoporosis: comparison of study designs and outcomes Narrative review, bibliography in large clinical trials with fracture as an endpoint Early effects of raloxifene on clinical vertebral fractures at 12 months in postmenopausal women with Subgroup analysis of included RCT Strontium ranelate prevents quality of life impairment in post-menopausal women with established Does not report relevant outcome vertebral osteoporosis Safety assessment of raloxifene over eight years in a clinical trial setting Not specific to fracture patients AAOS Clinical Practice Guidelines Unit Table 96 Excluded Articles and Reason for Exclusion
Author Title
Reason for Exclusion
Kyphoplasty: indications, contraindications and technique Less than 10 patients meeting inclusion criteria Effects of cyclical etidronate combined with calcitriol versus cyclical etidronate alone on spine and Not specific to fracture patients femoral neck bone mineral density in postmenopausal osteoporotic women Vertebroplasty versus kyphoplasty: A comparison and contrast Vertebral compression fractures: manage aggressively to prevent sequelae Narrative review, bibliography screened Complications following Harrington instrumentation for fractures of the thoracolumbar spine Retrospective case series 1150 kyphoplasties over 7 years: indications, techniques, and intraoperative complications Not best available evidence Effects of clodronate on vertebral fracture risk in osteoporosis: a 1-year interim analysis Not specific to fracture patients The effect of operator variability and experience in vertebroplasty outcomes Not relevant, comparison of surgeon experience Vertebroplasty and kyphoplasty for the treatment of vertebral compression fractures: an evidenced- Systematic review, bibliography based review of the literature Predictive value of intraosseous venography before percutaneous vertebroplasty Retrospective case series Prospective evaluation of pain relief in 100 patients undergoing percutaneous vertebroplasty: results Not best available evidence Quality of life following vertebroplasty Not best available evidence Reporting height restoration in vertebral compression fractures Does not investigate efficacy of treatment The biomechanics of long versus short fixation for thoracolumbar spine fractures Narrative review, bibliography screened Vertebroplasty for osteoporotic spine fracture: prevention and treatment Narrative review, bibliography screened Seven years of treatment with risedronate in women with postmenopausal osteoporosis Not best available evidence Epidemiology of vertebral fractures: implications for vertebral augmentation Does not investigate efficacy of treatment Strontium ranelate prevented vertebral fractures in postmenopausal women with osteoporosis Design and methodology of the phase 3 trials for the clinical development of strontium ranelate in the Description of study design treatment of women with postmenopausal osteoporosis Combined use of teriparatide and TNFalpha blockade: safety Less than 10 patients per group AAOS Clinical Practice Guidelines Unit Table 96 Excluded Articles and Reason for Exclusion
Author Title
Reason for Exclusion
Vitamin K(2) (menaquinone 4) reduces serum undercarboxylated osteocalcin level as early as 2 weeks Does not report patient oriented in elderly women with established osteoporosis Denosumab: anti-RANKL antibody Non-vertebral fracture risk reduction with oral bisphosphonates: challenges with interpreting clinical Systematic review, bibliography Once-monthly oral ibandronate compared with weekly oral alendronate in postmenopausal Not specific to fracture patients osteoporosis: Results from the head-to-head MOTION study Weekly oral alendronic Acid in male osteoporosis Not specific to fracture patients Cyclical etidronate in the treatment of postmenopausal osteoporosis: efficacy and safety after seven Follow-up study to included RCT years of treatment Risedronate for prevention of bone mineral density loss in patients receiving high-dose Not specific to fracture patients glucocorticoids: A randomized double-blind placebo-controlled trial Vertebroplasty and kyphoplasty: Biomechanics, outcomes, and complications Narrative review, bibliography screened Stabilisation of fractured thoracic and lumbar spine with Cotrel-Dubousset instrument Incorrect patient population Three-year effectiveness of intravenous pamidronate versus pamidronate plus slow-release sodium Incorrect patient population fluoride for postmenopausal osteoporosis Vertebroplasty: techniques to avoid complications Retrospective case series Pharmacological treatment of osteoporosis for people over 70 Narrative review, bibliography screened Treatment of thoracolumbar burst fractures without neurologic deficit by indirect reduction and Retrospective case series posterior instrumentation: bisegmental stabilization with monosegmental fusion Effect of alendronate and MK-677 (a growth hormone secretagogue), individually and in combination, Incorrect patient population on markers of bone turnover and bone mineral density in postmenopausal osteoporotic women Antiresorption therapy and reduction in fracture susceptibility in the osteoporotic elderly patient: open Not specific to fracture patients Vertebroplasty in the treatment of back pain Does not report validated, patient oriented outcomes Treatment of the vertebral crush fracture syndrome with enteric-coated sodium fluoride tablets and Retrospective case series calcium supplements The importance of genetic and nutritional factors in responses to vitamin D and its analogs in Narrative review, bibliography osteoporotic patients AAOS Clinical Practice Guidelines Unit Table 96 Excluded Articles and Reason for Exclusion
Author Title
Reason for Exclusion
Calcium phosphate cement-based vertebroplasty compared with conservative treatment for Not best available evidence osteoporotic compression fractures: a matched case-control study Calcium phosphate cement leakage after percutaneous vertebroplasty for osteoporotic vertebral Not best available evidence fractures: risk factor analysis for cement leakage Percutaneous transpedicular vertebroplasty with calcium phosphate cement in the treatment of Retrospective case series osteoporotic vertebral compression and burst fractures The response to calcitriol therapy in postmenopausal osteoporotic women is a function of initial Does not report patient oriented calcium absorptive status The effect of alendronate on progression of spinal osteophytes and disc-space narrowing Does not report relevant outcome Effect of alendronate on limited-activity days and bed-disability days caused by back pain in Does not report relevant outcome postmenopausal women with existing vertebral fractures. Fracture Intervention Trial Research Group Association of prevalent vertebral fractures, bone density, and alendronate treatment with incident Post hoc analysis vertebral fractures: effect of number and spinal location of fractures. The Fracture Intervention Trial Research Group Osteoporotic vertebral burst fractures with neurologic compromise Retrospective case series Osteoporotic vertebral fracture in clinical practice. 669 Patients diagnosed over a 10 year period Does not investigate efficacy of treatment A review of complications associated with vertebroplasty and kyphoplasty as reported to the Food and Narrative review, bibliography Drug Administration medical device related web site Obermayer Pietsch 2008 Effects of two years of daily teriparatide treatment on BMD in postmenopausal women with severe Not specific to fracture patients osteoporosis with and without prior antiresorptive treatment The impact of incident vertebral and non-vertebral fragility fractures on health-related quality of life in Does not investigate efficacy of established postmenopausal osteoporosis: results from the teriparatide randomized, placebo-controlled trial in postmenopausal women Vertebroplasty and kyphoplasty in the fractured osteoporotic spine Narrative review, bibliography screened Intravertebral cleft sign on fat-suppressed contrast-enhanced MR: correlation with cement distribution Retrospective case series pattern on percutaneous vertebroplasty Health-related quality of life in postmenopausal women with low BMD with or without prevalent Does not investigate efficacy of vertebral fractures Alendronate for the treatment of osteoporosis in men Cement augmentation techniques in traumatic thoracolumbar spine fractures Narrative review, bibliography screened AAOS Clinical Practice Guidelines Unit Table 96 Excluded Articles and Reason for Exclusion
Author Title
Reason for Exclusion
Less invasive anterior column reconstruction in thoracolumbar fractures Some complications of common treatment schemes of thoracolumbar spine fractures can be predicted Incorrect patient population with magnetic resonance imaging: prospective study of 53 patients with 71 fractures Ontario Ministry of Health Balloon kyphoplasty (Brief record) Systematic review, bibliography 7 Long Term Care 2004 Effects of 1 alpha-hydroxyvitamin D3 on lumbar bone mineral density and vertebral fractures in Not specific to fracture patients patients with postmenopausal osteoporosis Reduced occurrence of vertebral crush fractures in senile osteoporosis treated with 1 alpha (OH)- Insufficient data Lordoplasty: report on early results with a new technique for the treatment of vertebral compression Not best available evidence fractures to restore the lordosis Strontium ranelate: an increased bone quality leading to vertebral antifracture efficacy at all stages Narrative review, bibliography screened Bone histomorphometric changes after cyclic therapy with phosphate and etidronate disodium in Does not report patient oriented women with postmenopausal osteoporosis Calcitriol treatment is not effective in postmenopausal osteoporosis Not best available evidence A new biochemical marker of bone resorption for follow-up on treatment with nasal salmon calcitonin Not specific to fracture patients Long-term treatment of established osteoporosis with intranasal calcitonin Incorrect patient population Influence of the selective oestrogen receptor modulator (raloxifene hydrochloride) on IL-6, TNF- Not specific to fracture patients alpha, TGF-beta1 and bone turnover markers in the treatment of postmenopausal osteoporosis Calcitonin and calcium combined therapy in osteoporosis: effects on vertebra trabecular bone density Not best available evidence Sustained-release sodium fluoride in the management of established postmenopausal osteoporosis Insufficient data Effect of intermittent therapy with a slow-release fluoride preparation Insufficient data Safe and effective treatment of osteoporosis with intermittent slow release sodium fluoride: Not specific to fracture patients augmentation of vertebral bone mass and inhibition of fractures Effect of calcitonin and vitamin D in osteoporosis Not best available evidence Effectiveness of risedronate in osteoporotic postmenopausal women with inflammatory bowel disease: Not specific to fracture patients a prospective, parallel, open-label, two-year extension study Clinical results of an open prospective study of a bis-GMA composite in percutaneous vertebral Not best available evidence AAOS Clinical Practice Guidelines Unit Table 96 Excluded Articles and Reason for Exclusion
Author Title
Reason for Exclusion
Papadopoulos 2008 Unipedicular balloon kyphoplasty for the treatment of osteoporotic vertebral compression fractures: Not best available evidence Papaioannou 2006 Determinants of health-related quality of life in women with vertebral fractures Does not investigate efficacy of treatment Papaioannou 2002 Diagnosis and management of vertebral fractures in elderly adults Narrative review, bibliography screened Treatment of chronic mechanical spinal pain with intravenous pamidronate: a review of medical Incorrect patient population Urinary bone resorption markers in monitoring treatment of symptomatic osteoporosis Does not report patient oriented outcomes Effect of ipriflavone on bone mass in elderly osteoporotic women Insufficient reporting of outcomes Vertebroplasty and kyphoplasty for the management of osteoporotic vertebral compression fractures Narrative review, bibliography screened Neurologic deficit following percutaneous vertebral stabilization Less than 10 patients per group Double-blind, placebo-controlled study of the effects of tibolone on bone mineral density in Insufficient data postmenopausal osteoporotic women with and without previous fractures Percutaneous vertebroplasty: indications, contraindications, and technique Narrative review, bibliography screened Percutaneous vertebroplasty: a new technique for treatment of painful compression fractures The effects of alendronate treatment in osteoporotic patients affected by monoclonal gammopathy of Not specific to fracture patients undetermined significance Perez Higueras 2002 Percutaneous vertebroplasty: long-term clinical and radiological outcome Not best available evidence Pflugmacher 2009 Balloon kyphoplasty combined with posterior instrumentation for the treatment of burst fractures of Not best available evidence the spine--1-year results Pflugmacher 2006 Percutaneous balloon kyphoplasty in the treatment of pathological vertebral body fracture and Incorrect patient population deformity in multiple myeloma: a one-year follow-up Minimally invasive treatments of osteoporotic vertebral compression fractures Narrative review, bibliography screened Early radiographic and clinical results of balloon kyphoplasty for the treatment of osteoporotic Not best available evidence vertebral compression fractures Minimally invasive treatments of osteoporotic vertebral compression fractures: vertebroplasty and Narrative review, bibliography AAOS Clinical Practice Guidelines Unit Table 96 Excluded Articles and Reason for Exclusion
Author Title
Reason for Exclusion
Spinal body reconstruction in osteoporosis CT-guided vertebroplasty in osteoprotic vertebral fractures: incidence of secondary fractures and Not best available evidence impact of intradiscal cement leakages during follow-up CT-guided vertebroplasty: analysis of technical results, extraosseous cement leakages, and Not best available evidence complications in 500 procedures Percutaneous vertebroplasty as a treatment for osteoporotic vertebral compression fractures: a Systematic review, bibliography systematic review Intranasal salcatonin (salmon calcitonin). A review of its pharmacological properties and role in the Narrative review, bibliography management of postmenopausal osteoporosis Pongsoipetch 2007 Pain reduction in patients with painful vertebral compression fractures undergoing percutaneous Retrospective case series Sodium fluoride in the treatment of osteoporosis Not best available evidence Percutaneous vertebroplasty: new treatment for vertebral compression fractures The pathogenesis of age-related osteoporotic fracture: effects of dietary calcium deprivation Does not report patient oriented outcomes Analgesic effect of intranasal salmon calcitonin in the treatment of osteoporotic vertebral fractures Less than 10 patients per group Alendronate increases BMD at appendicular and axial skeletons in patients with established Not specific to fracture patients The effect of raloxifene therapy on the risk of new clinical vertebral fractures at three and six months: Not specific to fracture patients a secondary analysis of the MORE trial Effect of alendronate on vertebral fracture risk in women with bone mineral density T scores of-1.6 to Post hoc subgroup analysis -2.5 at the femoral neck: the Fracture Intervention Trial Monthly dosing with risedronate 50 mg on three consecutive days a month compared with daily Not specific to fracture patients dosing with risedronate 5 mg: a 6-month pilot study Research Reporting Standards for Percutaneous Vertebral Augmentation Characterization of patients in the European Forsteo Observational Study (EFOS): postmenopausal Does not investigate efficacy of women entering teriparatide treatment in a community setting Vertebroplasty for vertebral compression fracture Not best available evidence Oral Ibandronate Preserves Trabecular Microarchitecture: Micro-Computed Tomography Findings Does not report relevant outcome From the Oral Ibandronate Osteoporosis Vertebral Fracture Trial in North America and Europe Study Comparative effects of raloxifene and alendronate on fracture outcomes in postmenopausal women Incorrect patient population with low bone mass AAOS Clinical Practice Guidelines Unit Table 96 Excluded Articles and Reason for Exclusion
Author Title
Reason for Exclusion
Histomorphometric evaluation of daily and intermittent oral ibandronate in women with Does not report patient oriented postmenopausal osteoporosis: results from the BONE study Effects of long-term strontium ranelate treatment on the risk of nonvertebral and vertebral fractures in Not specific to fracture patients postmenopausal osteoporosis: Results of a five-year, randomized, placebo-controlled trial Efficacy and tolerability of once-monthly oral ibandronate in postmenopausal osteoporosis: 2 year Does not investigate efficacy of results from the MOBILE study Raloxifene reduces fractures in postmenopausal women with osteoporosis Narrative review, bibliography screened Importance of alfacalcidol in clinical conditions characterized by high rate of bone loss Narrative review, bibliography screened Strontium ranelate reduces the risk of nonvertebral fractures in postmenopausal women with Post hoc subgroup analysis osteoporosis: Treatment of Peripheral Osteoporosis (TROPOS) study Reduction in PINP, a marker of bone metabolism, with raloxifene treatment and its relationship with Not specific to fracture patients vertebral fracture risk Strontium ranelate phase 2 dose-ranging studies: PREVOS and STRATOS studies Report of parallel studies, identical results for applicable study reported in another article Strontium ranelate in osteoporosis Narrative review, bibliography screened Intermittent cyclic tiludronate in the treatment of osteoporosis Insufficient data The effect of sodium monofluorophosphate plus calcium on vertebral fracture rate in postmenopausal Not specific to fracture patients women with moderate osteoporosis. A randomized, controlled trial Efficacy and tolerability of calcitonin in the prevention and treatment of osteoporosis Narrative review, bibliography screened Design for an ipriflavone multicenter European fracture study Does not investigate efficacy of treatment Zoledronic acid and risedronate in the prevention and treatment of glucocorticoid-induced Not specific to fracture patients osteoporosis (HORIZON): a multicentre, double-blind, double-dummy, randomised controlled trial A comparison of the effect of alendronate and risedronate on bone mineral density in postmenopausal Does not report relevant outcome women with osteoporosis: 24-Month results from Addition of monofluorophosphate to estrogen therapy in postmenopausal osteoporosis: a randomized Not specific to fracture patients controlled trial Intermittent intravenous zoledronic acid increased bone mineral density in postmenopausal women Incorrect patient population AAOS Clinical Practice Guidelines Unit Table 96 Excluded Articles and Reason for Exclusion
Author Title
Reason for Exclusion
Estimated long-term effect of calcitonin treatment in acute osteoporotic spine fractures Does not report patient oriented outcomes Kyphoplasty: report of eighty-two thoracolumbar osteoporotic vertebral fractures Retrospective case series Salmon calcitonin reduces vertebral fracture rate in postmenopausal crush fracture syndrome Insufficient data Drug therapy for vertebral fractures in osteoporosis: evidence that decreases in bone turnover and Does not investigate efficacy of increases in bone mass both determine antifracture efficacy Treatment of primary osteoporosis with fluoride and calcium. Clinical tolerance and fracture Not best available evidence Absolute risk reduction in osteoporosis: assessing treatment efficacy by number needed to treat Narrative review, bibliography screened Sustained efficacy of risedronate in men with primary and secondary osteoporosis: results of a 2-year Not specific to fracture patients Potential of alfacalcidol for reducing increased risk of falls and fractures Narrative review, bibliography screened Efficacy of risedronate in men with primary and secondary osteoporosis: results of a 1-year study Not specific to fracture patients Alfacalcidol versus plain vitamin D in the treatment of glucocorticoid/inflammation-induced Narrative review, bibliography Alendronate treatment of established primary osteoporosis in men: 3-year results of a prospective, Not specific to fracture patients comparative, two-arm study Transdermal fentanyl for the treatment of back pain caused by vertebral osteoporosis Not best available evidence Treatment of male osteoporosis: recent advances with alendronate Narrative review, bibliography screened Monofluorophosphate combined with hormone replacement therapy in postmenopausal osteoporosis. Not best available evidence An open-label pilot efficacy and safety study Alendronate treatment of established primary osteoporosis in men: results of a 2-year prospective Not specific to fracture patients Treatment of osteoporosis in men with fluoride alone or in combination with bisphosphonates Incorrect patient population Long-term strategy in the management of postmenopausal osteoporosis Osteoporosis: non-hormonal treatment Long-term outcome of weekly bisphosphonates Narrative review, bibliography screened AAOS Clinical Practice Guidelines Unit Table 96 Excluded Articles and Reason for Exclusion
Author Title
Reason for Exclusion
Two-year results of once-weekly administration of alendronate 70 mg for the treatment of Not specific to fracture patients postmenopausal osteoporosis Kyphoplasty for the management of osteoporotic and malignant fractures of the spine Retrospective case series Spinal loads after osteoporotic vertebral fractures treated by vertebroplasty or kyphoplasty Biomechanical study The role of parathyroid hormone in the management of osteoporosis Narrative review, bibliography screened Can the prophylactic use of raloxifene, a selective estrogen-receptor modulator, prevent bone mineral loss and fractures in women with diagnosed osteoporosis or vertebral fractures? Once-monthly oral ibandronate in postmenopausal osteoporosis: translation and updated review Systematic review, bibliography screened Percutaneous vertebroplasty compared to conservative treatment in patients with painful acute or Not best available evidence subacute osteoporotic vertebral fractures: three-months follow-up in a clinical randomized study Prevalence of risk factors for referring post-menopausal women for bone densitometry. The Does not investigate efficacy of Strontium ranelate reduces the risk of vertebral fracture in young postmenopausal women with severe Post hoc subgroup analysis Intravenous clodronate for acute pain induced by osteoporotic vertebral fracture Treatment comparison not relevant Intermittent oral disodium pamidronate in established osteoporosis: A 2 year double-masked placebo- Not specific to fracture patients controlled study of efficacy and safety Single balloon kyphoplasty using far-lateral extrapedicular approach: technical note and preliminary Not best available evidence Teriparatide or alendronate in glucocorticoid-induced osteoporosis Not specific to fracture patients A comparison of continuous alendronate, cyclical alendronate and cyclical etidronate with calcitriol in Does not report relevant outcome the treatment of postmenopausal vertebral osteoporosis: a randomized controlled trial Percutaneous vertebroplasty performed by the isocenter puncture method Not specific to fracture patients Incidence and outcome of osteoporotic fractures in 2004 in Sado City, Niigata Prefecture, Japan Does not investigate efficacy of treatment The management of pain from collapse of osteoporotic vertebrae with continuous intrathecal Not best available evidence morphine infusion Relationships between bone mineral density and incident vertebral fracture risk with raloxifene Does not investigate efficacy of AAOS Clinical Practice Guidelines Unit Table 96 Excluded Articles and Reason for Exclusion
Author Title
Reason for Exclusion
Longterm effect of intermittent cyclical etidronate therapy on corticosteroid-induced osteoporosis in Incorrect patient population Japanese patients with connective tissue disease: 7-year followup Clinical inquiries. Who should receive vertebroplasty? Are there differences between men and women prescribed bisphosphonate therapy in canadian Does not investigate efficacy of subspecialty osteoporosis practices? Therapeutic equivalence of alendronate 70 mg once-weekly and alendronate 10 mg daily in the Not specific to fracture patients treatment of osteoporosis. Alendronate Once-Weekly Study Group Bone fragility of the peripheral skeleton during fluoride therapy for osteoporosis Not best available evidence Radiographic features of the spine in fluoride therapy for osteoporosis Not best available evidence Cost-effectiveness of alendronate therapy for osteopenic postmenopausal women Cost-effectiveness study Strontium ranelate reduces the risk of vertebral fractures in patients with osteopenia Post hoc subgroup analysis Relationship between pretreatment bone resorption and vertebral fracture incidence in postmenopausal Post hoc subgroup analysis osteoporotic women treated with risedronate Effects of two-levels, four-levels, and four-levels plus offset-hook posterior fixation techniques on Incorrect patient population protecting the surgical correction of unstable thoracolumbar vertebral fractures: A clinical study Vertebroplasty in the treatment of osteoporotic vertebral fractures: results and functional outcome in a Not best available evidence series of 175 consecutive patients Functional outcome of low lumbar burst fractures. A multicenter review of operative and nonoperative Incorrect patient population treatment of L3-L5 Continuous intrathecal morphine infusion in patients with vertebral fractures due to osteoporosis Not best available evidence Alendronate versus calcitriol for the prevention of bone loss after cardiac transplantation Not specific to fracture patients Osteoporotic vertebral compression fractures: a review of current surgical management techniques Narrative review, bibliography screened Vertebroplasty and kyphoplasty: treatment techniques for managing osteoporotic vertebral Narrative review, bibliography compression fractures Late instability in cervical spine fractures secondary to laminectomy Incorrect patient population Effects of 2 years' treatment of osteoporosis with 1 alpha-hydroxy vitamin D3 on bone mineral density Not specific to fracture patients and incidence of fracture: a placebo-controlled, double-blind prospective study Evaluation of the drug therapy for established osteoporosis by dual-energy x-ray absorptiometry Not specific to fracture patients A double-masked multicenter comparative study between alendronate and alfacalcidol in Japanese Not specific to fracture patients patients with osteoporosis. The Alendronate Phase III Osteoporosis Treatment Research Group AAOS Clinical Practice Guidelines Unit Table 96 Excluded Articles and Reason for Exclusion
Author Title
Reason for Exclusion
Efficacy of bazedoxifene in reducing new vertebral fracture risk in postmenopausal women with Insufficient data osteoporosis: results from a 3-year, randomized, placebo-, and active-controlled clinical trial Comparison of fracture, cardiovascular event, and breast cancer rates at 3 years in postmenopausal Does not investigate efficacy of women with osteoporosis The analgesic role of calcitonin following osteoporotic fracture Narrative review, bibliography screened The relationship of health-related quality of life to prevalent and incident vertebral fractures in Does not investigate efficacy of postmenopausal women with osteoporosis: results from the Multiple Outcomes of Raloxifene Evaluation Study Prevention and management of osteoporosis: consensus statements from the Scientific Advisory Narrative review, bibliography Board of the Osteoporosis Society of Canada. 9. Calcitonin in the treatment of osteoporosis Kyphoplasty and functional outcomes in patients with osteoporotic fractures: Commentary Osteoporotic compression fractures: outcomes after single- versus multiple-level percutaneous Not best available evidence Effects of risedronate on fracture risk in postmenopausal women with osteopenia Not specific to fracture patients Effects of raloxifene on fracture severity in postmenopausal women with osteoporosis: results from follow up analysis of included RCT the MORE study. Multiple Outcomes of Raloxifene Evaluation Alendronate in the treatment of osteoporosis: a review of the clinical trials Narrative review, bibliography screened Long-term efficacy of risedronate: a 5-year placebo-controlled clinical experience Less than 50% follow-up Effect of two forms of alendronate administration upon bone mass after two years of treatment Not specific to fracture patients Physiotherapy and osteoporosis: practice behaviors and clinicians' perceptions--a survey Does not investigate efficacy of treatment Nonoperative treatment of thoracic and lumbar spine fractures: a prospective randomized study of Incorrect patient population different treatment options Monthly oral ibandronate is effective and well tolerated after 3 years: the MOBILE long-term Does not investigate efficacy of A randomized study on the effects of estrogen/gestagen or high dose oral calcium on trabecular bone Does not report patient oriented remodeling in postmenopausal osteoporosis Five years of treatment with risedronate and its effects on bone safety in women with postmenopausal Not best available evidence AAOS Clinical Practice Guidelines Unit Table 96 Excluded Articles and Reason for Exclusion
Author Title
Reason for Exclusion
Treatment of painful osteoporotic compression and burst fractures using kyphoplasty: a prospective Not best available evidence observational design Five years of clinical experience with intermittent cyclical etidronate for postmenopausal osteoporosis Not best available evidence Effect of intermittent cyclical etidronate therapy on bone mass and fracture rate in women with Insufficient data postmenopausal osteoporosis Cost-effectiveness of balloon kyphoplasty in patients with symptomatic vertebral compression Cost-effectiveness study fractures in a UK setting A randomized study of tibolone on bone mineral density in osteoporotic postmenopausal women with Not specific to fracture patients previous fractures Vertebroplasty: The alternative treatment for osteoporotic vertebral compression fractures in the Retrospective case series Three-year calcitonin combination therapy for postmenopausal osteoporosis with crush fractures of Insufficient data Effect of vitamin K and/or D on undercarboxylated and intact osteocalcin in osteoporotic patients with Does not report patient oriented vertebral or hip fractures Differences of therapeutic effects on regional bone mineral density and markers of bone mineral Incorrect patient population metabolism between alendronate and alfacalcidol in Japanese osteoporotic women Relationship between cement distribution pattern and new compression fracture after percutaneous Not best available evidence Back pain, vertebroplasty, and kyphoplasty: Treatment of osteoporotic vertebral compression fractures Narrative review, bibliography screened Balloon kyphoplasty in the management of vertebral compression fractures: an updated systematic Systematic review, bibliography review and meta-analysis Balloon kyphoplasty and vertebroplasty for vertebral compression fractures: a comparative systematic Systematic review, bibliography review of efficacy and safety Follow-up on percutaneous vertebroplasty using PMMA in osteoporotic patients Retrospective case series A simplified method of opacifying and mixing acrylic cement for percutaneous vertebroplasty: a Not best available evidence clinical and in vitro study Kyphosis correction and height restoration effects of percutaneous vertebroplasty Retrospective case series Long segment instrumentation of thoracolumbar burst fracture: Fusion versus nonfusion Not relevant, comparison not considered for this guideline AAOS Clinical Practice Guidelines Unit Table 96 Excluded Articles and Reason for Exclusion
Author Title
Reason for Exclusion
Posterior fixation of thoracolumbar burst fracture: short-segment pedicle fixation versus long-segment Incorrect patient population Percutaneous balloon kyphoplasty for the correction of spinal deformity in painful vertebral body Not best available evidence compression fractures Recurrence of vertebral fracture with cyclical etidronate therapy in osteoporosis: histomorphometry Not best available evidence and X-Ray microanalysis evaluation Effects of simvastatin on bone mineral density and remodeling parameters in postmenopausal Incorrect patient population osteopenic subjects: 1-year follow-up study 1,25-dihydroxyvitamin D3 (calcitriol) in the treatment of postmenopausal osteoporosis Insufficient data, n per group not reported Therapies for treatment of osteoporosis in US women: cost-effectiveness and budget impact Cost-effectiveness study Improvement in bone strength parameters. The role of strontium ranelate Does vertebroplasty cause incident vertebral fractures? A review of available data Systematic review, bibliography screened New fractures after vertebroplasty: adjacent fractures occur significantly sooner Retrospective case series Subsequent vertebral fractures after vertebroplasty: association with intraosseous clefts Retrospective case series A randomized trial of nasal spray salmon calcitonin in men with idiopathic osteoporosis: Effects on Not specific to fracture patients bone mineral density and bone markers The effectiveness of cyclic and continuous oral clodronate therapy on bone density and markers in Not specific to fracture patients osteopenic postmenopausal women Effects of alendronate combined with hormone replacement therapy on osteoporotic postmenopausal Incorrect patient population Sacral insufficiency fractures: current concepts of management Narrative review, bibliography screened Percutaneous vertebroplasty in the management of osteoporotic vertebral compression fractures: Not best available evidence initial experience Back pain treatment in post-menopausal osteoporosis with vertebral fractures Occurrence of new vertebral body fracture after percutaneous vertebroplasty in patients with Retrospective case series AAOS Clinical Practice Guidelines Unit Table 96 Excluded Articles and Reason for Exclusion
Author Title
Reason for Exclusion
Effects of risedronate 5 mg/d on bone mineral density and bone turnover markers in late- Not specific to fracture patients postmenopausal women with osteopenia: a multinational, 24-month, randomized, double-blind, placebo-controlled, parallel-group, phase III trial Percutaneous cement injection into a created cavity for the treatment of vertebral body fracture: Retrospective case series preliminary results of a new vertebroplasty technique The cost-effectiveness of bisphosphonates in postmenopausal women based on individual long-term Cost-effectiveness study Vasconcelos 2002 Is percutaneous vertebroplasty without pretreatment venography safe? Evaluation of 205 consecutives Not best available evidence Sacral fractures after multi-segmental lumbosacral fusion: a series of four cases and systematic review Anterior spinal column augmentation with injectable bone cements Narrative review, bibliography screened Balloon vertebroplasty in combination with pedicle screw instrumentation: a novel technique to treat Incorrect patient population thoracic and lumbar burst fractures Vertebral body replacement system Synex in unstable burst fractures of the thoracic and lumbar spine Incorrect patient population CT-guided percutaneous vertebroplasty in the therapy of vertebral compression fractures Retrospective case series Postural correction by osteoporosis orthosis (Osteo-med): A randomized, placebo-controlled trial Not specific to fracture patients The risk of new osteoporotic vertebral compression fractures in the year after percutaneous Not best available evidence Prospective clinical follow-up after percutaneous vertebroplasty in patients with painful osteoporotic Not best available evidence vertebral compression fractures Pain response in the first trimester after percutaneous vertebroplasty in patients with osteoporotic Not best available evidence vertebral compression fractures with or without bone marrow edema Vertebroplasty and the randomized study: Where science and ethics collide Relationship between changes in bone mineral density and vertebral fracture risk associated with Does not investigate efficacy of risedronate: greater increases in bone mineral density do not relate to greater decreases in fracture risk Risedronate prevents new vertebral fractures in postmenopausal women at high risk Post hoc subgroup analysis of included RCT's Use of matched historical controls to evaluate the anti-fracture efficacy of once-a-week risedronate Not specific to fracture patients Risedronate for the prevention and treatment of postmenopausal osteoporosis: results from recent Narrative review, bibliography AAOS Clinical Practice Guidelines Unit Table 96 Excluded Articles and Reason for Exclusion
Author Title
Reason for Exclusion
Treatment of painful osteoporotic vertebral fractures with percutaneous vertebroplasty or kyphoplasty Systematic review, bibliography screened The clinical tolerability profile of alendronate Narrative review, bibliography screened WCB Evidence Based Percutaneous vertebroplasty for pain relief in the management of compressive vertebral fractures Systematic review, bibliography Practice Group 2003 (Structured abstract) Surgically controlled, transpedicular methyl methacrylate vertebroplasty with fluoroscopic guidance Not best available evidence Sacroplasty versus vertebroplasty: comparable clinical outcomes for the treatment of fracture-related Retrospective case series Bisphosphonates and osteoporotic fractures: a cross-design synthesis of results among Systematic review, bibliography compliant/persistent postmenopausal women in clinical practice versus randomized controlled trials Wimalawansa 2000 Prevention and treatment of osteoporosis: efficacy of combination of hormone replacement therapy Narrative review, bibliography with other antiresorptive agents Treatment of pain from osteoporotic vertebral collapse by percutaneous PMMA vertebroplasty Not best available evidence Anterior versus posterior surgical treatment for traumatic cervical spine dislocation Xenodemetropoulos 2004 The impact of fragility fracture on health-related quality of life : the importance of antifracture therapy Narrative review, bibliography screened The efficacy and safety of calcitriol and/or Caltrate D in elderly Chinese women with low bone mass Not specific to fracture patients The efficacy and tolerability of once-weekly alendronate 70 mg on bone mineral density and bone Not specific to fracture patients turnover markers in postmenopausal Chinese women with osteoporosis Osteoporosis management in prostate cancer patients treated with androgen deprivation therapy Does not investigate efficacy of treatment Efficacy and safety of balloon kyphoplasty in the treatment of osteoporotic vertebral body Not best available evidence compression fractres: Compared with vertebroplasty Operative versus non-operative treatment for thoracolumbar burst fractures without neurological Systematic review, bibliography Health-related quality of life (HRQOL) in Japanese osteoporotic patients and its improvement by Not best available evidence elcatonin treatment Management of painful osteoporotic vertebral compression fractures: Vertebroplasty and kyphoplasty Narrative review, bibliography screened Early clinical experience with the Syracuse I-Plate: an anterior spinal fixation device Retrospective case series AAOS Clinical Practice Guidelines Unit Table 96 Excluded Articles and Reason for Exclusion
Author Title
Reason for Exclusion
Effects of teriparatide [recombinant human parathyroid hormone (1-34)] on cortical bone in Does not report patient oriented postmenopausal women with osteoporosis Effect of high doses of oral risedronate (20 mg/day) on serum parathyroid hormone levels and urinary Less than 10 patients per group collagen cross-link excretion in postmenopausal women with spinal osteoporosis A clinical study of Yigu capsule in treating postmenopausal osteoporosis Not specific to fracture patients Effects of combined treatment of Rocaltrol, Etidronate and Sisterly on bone pain and bone mineral Not best available evidence density in osteoporosis patients with vertebral fracture Pharmacologic prevention of osteoporotic fractures Narrative review, bibliography screened Percutaneous vertebroplasty for osteoporotic compression fractures: quantitative prospective Not best available evidence evaluation of long-term outcomes AAOS Clinical Practice Guidelines Unit

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