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Guideline Summary
Guideline Title
Atypical subtrochanteric and diaphyseal femoral fractures: report of a task force of the American Society for Bone and Mineral Research.
Bibliographic Source(s)
Shane E, Burr D, Ebeling PR, Abrahamsen B, Adler RA, Brown TD, Cheung AM, Cosman F, Curtis JR, Dell R, Dempster D, Einhorn TA, Genant HK, Geusens P, Klaushofer K, Koval K, Lane JM, McKiernan F, McKinney R, Ng A, Nieves J, O'Keefe R, Papapoulos S, Sen HT, van der Meulen MC, Weinstein RS, Whyte M, American Society for Bone and Mineral Research. Atypical subtrochanteric and diaphyseal femoral fractures: report of a task force of the American Society for Bone and Mineral Research. J Bone Miner Res. 2010 Nov;25(11):2267-94. [177 references] PubMed External Web Site Policy
Guideline Status

This is the current release of the guideline.

Scope

Disease/Condition(s)

Atypical subtrochanteric and diaphyseal femoral fractures

Note: The diagnosis of atypical femoral fractures should specifically exclude fractures of the femoral neck, intertrochanteric fractures with spiral subtrochanteric extension, pathologic fractures associated with local primary or metastatic bone tumors, and periprosthetic fractures.

Guideline Category
Diagnosis
Evaluation
Management
Prevention
Treatment
Clinical Specialty
Endocrinology
Family Practice
Geriatrics
Internal Medicine
Orthopedic Surgery
Radiology
Intended Users
Physician Assistants
Physicians
Guideline Objective(s)
  • To assist in case finding and reporting by defining major and minor features for complete and incomplete atypical fractures of the femur
  • To provide treatment recommendations for atypical subtrochanteric and diaphyseal femoral fractures
Target Population

Patients with known or suspected atypical subtrochanteric and diaphyseal femoral fractures

Interventions and Practices Considered

Diagnosis/Evaluation

Noninvasive diagnostic and imaging techniques

  • Anteroposterior and lateral plain radiographs of hip, including diaphysis of femur
  • Scintigraphy or magnetic resonance imaging (MRI) of the femur

Treatment/Management

Orthopedic Management

  1. Complete subtrochanteric/diaphyseal femoral fractures:
    • Stabilization of fracture
    • Endochondral fracture repair
  2. Incomplete subtrochanteric/diaphyseal femoral fractures:
    • If minimal pain, conservative therapy, such as use of crutches or walker and limited activity
    • If accompanied with pain, prophylactic nail fixation

Medical Management

  1. Assessment of benefits and risks before use of pharmacologic treatment (e.g., bisphosphonates [BPs])
  2. Annual reevaluation of BP therapy, particularly for low risk patients
  3. Clinical assessment of patients discontinuing BP usage, including bone turnover markers and bone mineral density (BMD) determination
  4. Physician and patient education on prodrome of thigh and groin pain
  5. Dietary calcium and vitamin D supplementation
Major Outcomes Considered
  • Incidence of groin or thigh pain
  • Duration of treatment with bisphosphonates and concomitant medications (e.g., glucocorticoids)
  • Incidence of comorbid conditions (diabetes, rheumatoid arthritis, vitamin D deficiency)
  • Changes in bone mineral density T-score and bone turnover markers
  • Sensitivity and specificity of imaging methods

Methodology

Methods Used to Collect/Select the Evidence
Searches of Electronic Databases
Description of Methods Used to Collect/Select the Evidence

Review of the Literature/Data Acquisition

A literature search using PubMed and OVID sought English-language articles with full text abstracts during the period January 1990 to April 30, 2010. The search terms specified included atypical fracture, subtrochanteric fracture, femoral fracture, diaphyseal fracture, shaft fracture, cortical fracture, bilateral fracture, transverse fracture, low-energy fracture, spontaneous fracture, insufficiency fracture, stress fracture, bisphosphonates, antiresorptive, bone turnover, alendronate, pamidronate, etidronate, ibandronate, risedronate, zoledronate, zoledronic acid, Didronel, Actonel, Fosamax, Reclast, and Boniva.

Identification of case duplication between studies was achieved by cross-referencing studies whenever possible.

Number of Source Documents

Not stated

Methods Used to Assess the Quality and Strength of the Evidence
Expert Consensus
Rating Scheme for the Strength of the Evidence

Not applicable

Methods Used to Analyze the Evidence
Systematic Review with Evidence Tables
Description of the Methods Used to Analyze the Evidence

The abstracts retrieved were reviewed by one coauthor to assess their relevance to atypical fractures or long-term complications of bisphosphonates (BPs), and full text articles of each abstract selected were reviewed subsequently by four members of the American Society of Bone and Mineral Research (ASBMR) task force in order to construct the relevant sections of this article.

The numbers of subjects in each study; the age and sex of subjects; the specific BP(s) used (if any); the dose and duration of BP exposure; the clinical presentation; a prodrome of pain; the characteristics of the reported fracture(s); the level of trauma; the presence of either bilateral fractures or bilateral radiologic changes and comorbid conditions such as rheumatoid arthritis (RA) and diabetes mellitus (DM); the concomitant use of other antiresorptive drugs, glucocorticoids (GCs), or proton pump inhibitors (PPIs); the presence of vitamin D deficiency (<20 ng/mL); the presence of a bone mineral density (BMD) T-score greater than –2.5 (osteopenia or normal BMD); information on bone histology; management and outcome; and any other information were included, when available.

The evidence tables (Tables 5 and 6) used by the task force are provided in the original guideline document.

Methods Used to Formulate the Recommendations
Expert Consensus
Description of Methods Used to Formulate the Recommendations

The Expert Committee

The expert committee consisted of an international multidisciplinary group of 28 individuals with expertise in clinical and basic bone biology, endocrinology, epidemiology, radiology, biomechanics, and orthopedic surgery. The expert committee also included a basic scientist working in the bone field but not in the areas of osteoporosis and bisphosphonates (BPs) and a physician and bioethicist with expertise in conflict issues affecting biomedical researchers.

This task force was asked to:

  1. Make a recommendation for a provisional case definition of atypical femoral fractures so that subsequent studies report on the same condition.
  2. Review carefully the currently available information in order to assess what is actually known and what is not known about atypical femoral fractures and their potential relationship with BP usage.
  3. Recommend the development of noninvasive diagnostic and imaging techniques with which to better characterize and diagnose the disorder.
  4. Identify the key questions that the scientific community should address and recommend a research agenda to elucidate incidence, pathophysiology, and etiology of atypical femoral fractures and their potential relationship with BP usage.
  5. Recommend clinical orthopedic and medical management of atypical femoral fractures based on available information.

The task force considered both preclinical and epidemiologic data, reviewed all case reports and series of atypical femoral fractures, and conducted interviews with physician and scientist representatives of pharmaceutical companies that market drugs for osteoporosis and the United States Food and Drug Administration (USFDA).

Input from the Pharmaceutical Industry

Four members of the task force conducted teleconference sessions with representatives of companies that market drugs used to treat osteoporosis in the United States (i.e., Amgen, Eli Lilly, Genentech, Merck, Novartis, and Warner-Chilcott). These sessions were informational; they permitted the task force to develop some understanding of the number of atypical fracture cases reported to the industry and the steps being taken by the individual companies to adjudicate cases reported to them. The sessions also permitted experts from the industry to provide their input on the case definition for consideration by the task force.

Input from the United States Food and Drug Administration (FDA)

Two task force members conducted a teleconference with representatives of the FDA. Data from the FDA were consistent with industry and task force estimates of the number of atypical femoral fractures. However, officials emphasized that adverse-event reporting was subject to the same limitations noted earlier, particularly substantial underreporting.

Rating Scheme for the Strength of the Recommendations

Not applicable

Cost Analysis

A formal cost analysis was not performed and published cost analyses were not reviewed.

Method of Guideline Validation
Not stated
Description of Method of Guideline Validation

Not applicable

Recommendations

Major Recommendations

Make a Recommendation for a Provisional Case Definition of Atypical Femoral Fractures So That Subsequent Studies Report on the Same Condition

To assist in case finding and reporting, the task force defined major and minor features for complete and incomplete atypical fractures of the femur (see the table below). All major features should be present in order to designate a fracture as atypical and distinguish it from more common hip fractures (i.e., femoral neck, intertrochanteric). Minor features commonly have been described in association with atypical fractures but may or may not be present in individual patients. Although atypical femoral fractures have been reported most prominently in individuals who have been treated with bisphosphonates (BPs), such fractures have been reported in individuals with no history of BP exposure. Therefore, to facilitate studies comparing the frequency of atypical femoral fractures in patients with and without BP therapy, association with BP therapy was included as a minor feature.

Table. Atypical Femoral Fracture: Major and Minor Featuresa

Major Featuresb

  • Located anywhere along the femur from just distal to the lesser trochanter to just proximal to the supracondylar flare
  • Associated with no trauma or minimal trauma, as in a fall from a standing height or less
  • Transverse or short oblique configuration
  • Noncomminuted
  • Complete fractures extend through both cortices and may be associated with a medial spike; incomplete fractures involve only the lateral cortex.

Minor Features

  • Localized periosteal reaction of the lateral cortexc
  • Generalized increase in cortical thickness of the diaphysis
  • Prodromal symptoms such as dull or aching pain in the groin or thigh
  • Bilateral fractures and symptoms
  • Delayed healing
  • Comorbid conditions (e.g., vitamin D deficiency, rheumatoid arthritis [RA], hypophosphatasia)
  • Use of pharmaceutical agents (e.g., BPs, glucocorticoids [GCs], proton pump inhibitors [PPIs])

aSpecifically excluded are fractures of the femoral neck, intertrochanteric fractures with spiral subtrochanteric extension, pathologic fractures associated with primary or metastatic bone tumors, and periprosthetic fractures.
bAll major features are required to satisfy the case definition of atypical femoral fracture. None of the minor features are required but sometimes have been associated with these fractures.
cOften referred to in the literature as beaking or flaring.

Recommend the Development of Noninvasive Diagnostic and Imaging Techniques with Which to Better Characterize and Diagnose the Disorder

Imaging of the atypical femoral shaft fracture is relatively straightforward. Conventional radiography is the first line of approach, with more sophisticated imaging such as bone scintigraphy, magnetic resonance imaging (MRI), or computed tomography (CT) useful principally for detecting early or subtle prefracture features.

While scintigraphy, MRI, and CT scanning are more costly and less convenient than conventional radiography, these advanced imaging techniques provide superior sensitivity and specificity for detecting early stages of stress or insufficiency fractures and therefore, in selected instances, could improve the clinical management of atypical femoral shaft fractures (see Figures 5A–C in the original guideline document). Even the lower-resolution images of dual-energy X-ray absorptiometry (DXA) occasionally may detect the hypertrophic new bone formation of an evolving proximal subtrochanteric femoral shaft fracture and aid in the differentiation of proximal thigh pain in this condition (see Figure 5D in the original guideline document).

Recommend Clinical Orthopedic and Medical Management of Atypical Femoral Fractures Based on Available Information

Surgical Treatment Strategy for Atypical Subtrochanteric and Femoral Shaft Fractures

Because of the propensity for delayed healing, the morbidity of these fractures is particularly high. The task force recognized that there are no controlled studies evaluating surgical treatment strategies for atypical subtrochanteric and femoral shaft fractures. The recommendations outlined here therefore are opinion-based and represent the consensus of the orthopedic surgeons who served on the task force. The task force developed a hierarchical approach to management that depends on whether the fracture is complete or incomplete.

History of Thigh or Groin Pain in a Patient on BP Therapy

A femoral fracture must be ruled out (Goh et al., 2007; Kwek et al., 2008; Lenart et al., 2009; Neviaser et al., 2008; Capeci & Tejwani, 2009; Odvina et al., 2010; Lenart, Lorich, & Lane, 2008; Das De, Setiobudi, & Shen, 2010). Anteroposterior and lateral plain radiographs of the hip, including the full diaphysis of the femur, should be performed. If the radiograph is negative and the level of clinical suspicion is high, a technetium bone scan or MRI of the femur should be performed to detect a periosteal stress reaction. The advantage of the technetium bone scan is that both legs will be imaged.

Complete Subtrochanteric/Diaphyseal Femoral Fracture

Orthopedic management includes stabilizing the fracture and addressing the medical management (Goh et al., 2007; Kwek et al., 2008; Lenart et al., 2009; Neviaser et al., 2008; Capeci & Tejwani, 2009; Odvina et al., 2010; Lenart, Lorich, & Lane, 2008; Das De, Setiobudi, & Shen, 2010) (see below). Since BPs inhibit osteoclastic remodeling, endochondral fracture repair is the preferred method of treatment. Intramedullary reconstruction full-length nails accomplish this goal and protect the entire femur. Locking plates preclude endochondral repair, have a high failure rate, and are not recommended as the method of fixation. The medullary canal should be overreamed (at least 2.5 mm larger than the nail diameter) to compensate for the narrow intramedullary diameter (if present), facilitate insertion of the reconstruction nail, and prevent fracture of the remaining shaft. The proximal fragment may require additional reaming to permit passage of the nail and avoid malalignment. The contralateral femur must be evaluated radiographically, including scintigraphy or MRI, whether or not symptoms are present (Capeci & Tejwani, 2009).

Incomplete Subtrochanteric/Femoral Shaft Fractures

Prophylactic reconstruction nail fixation is recommended for incomplete fractures accompanied by pain (Goh et al., 2007; Kwek et al., 2008; Lenart et al., 2009; Neviaser et al., 2008; Capeci & Tejwani, 2009; Odvina et al., 2010; Lenart, Lorich, & Lane, 2008; Das De, Setiobudi, & Shen, 2010). If the patient has minimal pain, a trial of conservative therapy, in which weight bearing is limited through the use of crutches or a walker, may be considered. However, if there is no symptomatic and radiographic improvement after 2 to 3 months of conservative therapy, prophylactic nail fixation should be strongly considered because these patients may progress to a complete fracture. For patients with incomplete fractures and no pain, weight bearing may be continued but should be limited and vigorous activity avoided. Reduced activity should be continued until there is no bone edema on MRI.

Medical Management of Atypical Subtrochanteric/Femoral Shaft Fractures

There are also no controlled studies evaluating medical treatment strategies for atypical subtrochanteric and femoral shaft fractures. The recommendations outlined here therefore are opinion-based and represent the consensus of the clinicians who served on the task force. The task force considered two main aspects of medical management.

Prevention

Decisions to initiate pharmacologic treatment, including BPs, to manage patients with osteoporosis should be made based on an assessment of benefits and risks. Patients who are deemed to be at low risk of osteoporosis-related fractures should not be started on BPs. For patients with osteoporosis in the spine and normal or only moderately reduced femoral neck or total-hip bone mineral density (BMD), one could consider alternative treatments for osteoporosis, such as raloxifene or teriparatide, depending on the severity of the patient's condition. It is apparent that therapy must be individualized and clinical judgment must be used because there will not always be sufficient evidence for specific clinical situations. BP therapy should be strongly considered to protect patients from rapid bone loss and increased fracture rates associated with clinical scenarios such as organ transplantation, endocrine or chemotherapy for breast or prostate cancer, and initiation of aromatase inhibitors and glucocorticoids (GCs). However, long-term BP therapy may not always be necessary in these clinical conditions (Cohen et al., 2006; Hershman et al., 2010). More research is needed to determine the most effective dose and duration of BPs in patients with secondary causes of rapid bone loss.

The optimal duration of BP treatment is not known. Based on current case reports and series, the median BP treatment duration in patients with atypical subtrochanteric and femoral shaft fractures is 7 years. For patients without a recent fracture and with femoral neck T-scores greater than –2.5 after the initial therapeutic course, consideration may be given to a "drug holiday" from BPs. Because some patients with atypical femoral fractures while on BPs were on concomitant therapy with GCs, estrogen, tamoxifen, or proton pump inhibitors (PPIs), continued BP therapy should be reevaluated, particularly in those deemed to be at low or only modestly elevated fracture risk. Whether discontinuation of BPs after 4 to 5 years in the lower-risk group will lead to fewer atypical subtrochanteric fractures is not known.

If BPs are discontinued, there are no data to guide when or whether therapy should be restarted. However, patients should be followed by clinical assessment, bone turnover markers, and BMD determination. Restarting osteoporosis therapy, either with BPs or with a different class of agent, can be considered in patients who appear to be at increasing fracture risk. Models to help assess risk in previously treated patients, after 1 or more years off therapy, are needed to help guide these therapeutic decisions. It seems apparent that there can be no general rule and that decisions to stop and/or restart therapy must be individualized.

More than half of patients reported with atypical femoral fractures have had a prodrome of thigh or groin pain before suffering an overt break. Thus it is important to educate physicians and patients about this symptom and for physicians to ask patients on BPs and other potent antiresorptive agents about thigh or groin pain. Complaints of thigh or groin pain in a patient on BPs require urgent radiographic evaluation of both femurs (even if pain is unilateral). If plain radiographs are normal or equivocal and clinical suspicion is high, MRI or radionuclide scintigraphy should be performed to identify stress reaction, stress fracture, or partial fracture of either femur. Other disorders, such as forms of osteomalacia, also should be considered (Whyte, 2009).

Medical Management

For patients with a stress reaction, stress fracture, or incomplete or complete subtrochanteric or femoral shaft fracture, potent antiresorptive agents should be discontinued. Dietary calcium and vitamin D status should be assessed, and adequate supplementation should be prescribed.

In the absence of evidence-based approaches, teriparatide should be considered in patients who suffer these fractures, particularly if there is little evidence of healing by 4 to 6 weeks after surgical intervention.

Clinical Algorithm(s)

None provided

Evidence Supporting the Recommendations

References Supporting the Recommendations
Type of Evidence Supporting the Recommendations

The type of evidence supporting the recommendations is not specifically stated.

The recommendations are opinion-based and represent the consensus of the orthopedic surgeons and clinicians who served on the task force.

Benefits/Harms of Implementing the Guideline Recommendations

Potential Benefits

Timely identification and adequate treatment of atypical subtrochanteric and diaphyseal femoral fractures

Potential Harms

Not stated

Qualifying Statements

Qualifying Statements
  • The task force recognized that there are no controlled studies evaluating surgical or medical treatment strategies for atypical subtrochanteric and femoral shaft fractures. Therefore, the recommendations are opinion-based and represent the consensus of the clinicians who served on the task force.
  • It is apparent that medical therapy must be individualized and clinical judgment must be used because there will not always be sufficient evidence for specific clinical situations.

Implementation of the Guideline

Description of Implementation Strategy

An implementation strategy was not provided.

Institute of Medicine (IOM) National Healthcare Quality Report Categories

IOM Care Need
Getting Better
Living with Illness
Staying Healthy
IOM Domain
Effectiveness
Patient-centeredness

Identifying Information and Availability

Bibliographic Source(s)
Shane E, Burr D, Ebeling PR, Abrahamsen B, Adler RA, Brown TD, Cheung AM, Cosman F, Curtis JR, Dell R, Dempster D, Einhorn TA, Genant HK, Geusens P, Klaushofer K, Koval K, Lane JM, McKiernan F, McKinney R, Ng A, Nieves J, O'Keefe R, Papapoulos S, Sen HT, van der Meulen MC, Weinstein RS, Whyte M, American Society for Bone and Mineral Research. Atypical subtrochanteric and diaphyseal femoral fractures: report of a task force of the American Society for Bone and Mineral Research. J Bone Miner Res. 2010 Nov;25(11):2267-94. [177 references] PubMed External Web Site Policy
Adaptation

Not applicable: The guideline was not adapted from another source.

Date Released
2010 Nov
Guideline Developer(s)
American Society for Bone and Mineral Research - Professional Association
Source(s) of Funding

Most of the American Society for Bone and Mineral Research (ASBMR) revenue comes from membership dues, fees paid to attend the Society's annual meeting, and subscriptions to ASBMR publications. Like many scientific, professional, and medical organizations, ASBMR also accepts grants from pharmaceutical companies, the federal government, and other entities to support its mission. ASBMR receives corporate support in the form of unrestricted educational grants from pharmaceutical companies, rental of exhibit space at its annual meeting, and paid advertisements in its journal.

Guideline Committee

Atypical Femoral Fractures (ASBMR) Task Force

Composition of Group That Authored the Guideline

Task Force Members: Elizabeth Shane (Co-chair), David Burr (Co-chair), Peter R Ebeling, Bo Abrahamsen, Robert A Adler, Thomas D Brown, Angela M Cheung, Felicia Cosman, Jeffrey R Curtis, Richard Dell, David Dempster, Thomas A Einhorn, Harry K Genant, Piet Geusens, Klaus Klaushofer, Kenneth Koval, Joseph M Lane, Fergus McKiernan, Ross McKinney, Alvin Ng, Jeri Nieves, Regis O'Keefe, Socrates Papapoulos, Howe Tet Sen, Marjolein CH van der Meulen, Robert S Weinstein, and Michael Whyte

Financial Disclosures/Conflicts of Interest

American Society for Bone and Mineral Research (ASBMR) Disclosures

To ensure that the Society adheres to the highest ethical practices, ASBMR has an ethics committee, consults with experts in health care ethics, and periodically reviews its practices with regard to managing potential conflict of interest.

Although task force members were required to disclose their potential conflicts of interest and their disclosures are published in the original guideline document, ASBMR recognizes that this might not go far enough to demonstrate to some that the final output of the task force is free of all bias. In an effort to address this concern, two additional individuals were assigned to the Atypical Femoral Fractures Task Force—an ethicist and a scientist knowledgeable about the musculoskeletal system who does not work directly on osteoporosis or bisphosphonates or with pharmaceutical companies who make or market bisphosphonates. The role of these individuals was to provide ethical oversight to the work of the task force. Both individuals have verified and attested that they witnessed no commercial bias during the task force's deliberations, during discussions with the pharmaceutical industry, or in the preparation of the final document by the task force.

Task force members' individual conflicts of interest are available in a table in the original guideline document.

Guideline Status

This is the current release of the guideline.

Guideline Availability

Electronic copies: Available from the Journal of Bone and Mineral Research Web site External Web Site Policy.

Availability of Companion Documents

None available

Patient Resources

None available

NGC Status

This NGC summary was completed by ECRI Institute on November 6, 2012. The information was verified by the guideline developer on December 5, 2012.

Copyright Statement

Copyright ©2010 American Society for Bone and Mineral Research. May not be reproduced without permission.

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