Evolving Data about Subtrochanteric Fractures and Bisphosphonates

Shane, Elizabeth

doi:10.1056/nejme1003064

Cited by 76 publications

(53 citation statements)

References 8 publications

(1 reference statement)

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“…Although the FLEX data that compare 5 and 10 years of alendronate treatment provide some reassurance regarding reported associations of subtrochanteric/diaphyseal fracture with long-term BP treatment, this study had a number of very important limitations. (98) Radiographs were not available to evaluate features of atypia.…”

Section: Epidemiology Of Subtrochanteric and Femoral Shaft Fracturesmentioning

confidence: 99%

Atypical subtrochanteric and diaphyseal femoral fractures: Report of a task force of the american society for bone and mineral Research

Shane

Burr

Ebeling

et al. 2010

Journal of Bone and Mineral Research

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972

679

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Reports linking long-term use of bisphosphonates (BPs) with atypical fractures of the femur led the leadership of the American Society for Bone and Mineral Research (ASBMR) to appoint a task force to address key questions related to this problem. A multidisciplinary expert group reviewed pertinent published reports concerning atypical femur fractures, as well as preclinical studies that could provide insight into their pathogenesis. A case definition was developed so that subsequent studies report on the same condition. The task force defined major and minor features of complete and incomplete atypical femoral fractures and recommends that all major features, including their location in the subtrochanteric region and femoral shaft, transverse or short oblique orientation, minimal or no associated trauma, a medial spike when the fracture is complete, and absence of comminution, be present to designate a femoral fracture as atypical. Minor features include their association with cortical thickening, a periosteal reaction of the lateral cortex, prodromal pain, bilaterality, delayed healing, comorbid conditions, and concomitant drug exposures, including BPs, other antiresorptive agents, glucocorticoids, and proton pump inhibitors. Preclinical data evaluating the effects of BPs on collagen cross-linking and maturation, accumulation of microdamage and advanced glycation end products, mineralization, remodeling, vascularity, and angiogenesis lend biologic plausibility to a potential association with long-term BP use. Based on published and unpublished data and the widespread use of BPs, the incidence of atypical femoral fractures associated with BP therapy for osteoporosis appears to be very low, particularly compared with the number of vertebral, hip, and other fractures that are prevented by BPs. Moreover, a causal association between BPs and atypical fractures has not been established. However, recent observations suggest that the risk rises with increasing duration of exposure, and there is concern that lack of awareness and underreporting may mask the true incidence of the problem. Given the relative rarity of atypical femoral fractures, the task force recommends that specific diagnostic and procedural codes be created and that an international registry be established to facilitate studies of the clinical and genetic risk factors and optimal surgical and medical management of these fractures. Physicians and patients should be made aware of the possibility of atypical femoral fractures and of the potential for bilaterality through a change in labeling of BPs. Research directions should include development of animal models, increased surveillance, and additional epidemiologic and clinical data to establish the true incidence of and risk factors for this condition and to inform orthopedic and medical management. ß

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Section: Epidemiology Of Subtrochanteric and Femoral Shaft Fracturesmentioning

confidence: 99%

Atypical subtrochanteric and diaphyseal femoral fractures: Report of a task force of the american society for bone and mineral Research

Shane

Burr

Ebeling

et al. 2010

Journal of Bone and Mineral Research

Self Cite

972

679

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“…Bisphosphonate-associated stress fractures in the femur have been identified and characterized and are considered a risk for patients receiving long-term bisphosphonate therapy [7,10,11,14,20]. The true fracture risk associated with bisphosphonates is unclear as recent epidemiologic studies suggest modest to no increased risk with relative hazard ratios 1.03-1.50 compared with placebo [2,15,22]. However confidence intervals were wide (95% CI, 0.06- 16.46) making the results difficult to interpret [2,15,22].…”

Section: Introductionmentioning

confidence: 99%

“…The true fracture risk associated with bisphosphonates is unclear as recent epidemiologic studies suggest modest to no increased risk with relative hazard ratios 1.03-1.50 compared with placebo [2,15,22]. However confidence intervals were wide (95% CI, 0.06- 16.46) making the results difficult to interpret [2,15,22]. These stress fractures can be seen on plain radiographs as simple transverse patterns, with unicortical beaking and hypertrophy of the diaphyseal cortex [14] (Fig.…”

Section: Introductionmentioning

confidence: 99%

Nonoperative versus Prophylactic Treatment of Bisphosphonate-associated Femoral Stress Fractures

Banffy

Vrahas

Ready

et al. 2011

Clinical Orthopaedics &Amp; Related Research

115

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Background Several studies have identified a specific fracture in the proximal diaphysis of the femur in patients treated with bisphosphonates. The fractures typically are sustained after a low-energy mechanism with the presence of an existing characteristic stress fracture. However, it is unclear whether these patients are best treated nonoperatively or operatively. Questions/purposes What is the likelihood of nonoperatively treated bisphosphonate-associated femoral stress fractures progressing to completion and during what time period? If prophylactic fixation is performed, do patients have a shorter hospital length-of-stay compared with patients having surgical fixation after fracture completion? Patients and Methods We retrospectively searched for patients older than 50 years receiving bisphosphonate therapy, with either incomplete, nondisplaced stress fractures or completed, displaced fractures in the proximal diaphysis of the femur between July 2002 and April 2009. After applying exclusion criteria, we identified 34 patients with a total of 40 bisphosphonate-associated fractures. The average duration of bisphosphonate use was 77 months. Twenty-eight of 40 (70%) fractures were completed, displaced fractures. Six of the 12 nondisplaced stress fractures initially were treated nonoperatively. The remaining six stress fractures were treated with prophylactic cephalomedullary nail fixation. The minimum followup was 12 months (mean, 36.5 months; range, 12-72 months).

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“…Bisphosphonates in particular significantly inhibit bone resorption by suppressing osteoclast activity and increasing bone density [1][2][3]. Alendronate is one of these bisphosphonates; it was approved in the United States in the 1990s and is commonly prescribed worldwide [1,4,5]. Clinical trials have shown its effectiveness in the treatment of fractures related to postmenopausal osteoporosis [6].…”

Section: Introductionmentioning

confidence: 99%

Histological finding of atypical subtrochanteric fracture after long-term alendronate therapy

Kajino

Kabata

Watanabe

et al. 2012

Journal of Orthopaedic Science

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Evolving Data about Subtrochanteric Fractures and Bisphosphonates

Cited by 76 publications

References 8 publications

Atypical subtrochanteric and diaphyseal femoral fractures: Report of a task force of the 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

Nonoperative versus Prophylactic Treatment of Bisphosphonate-associated Femoral Stress Fractures

Histological finding of atypical subtrochanteric fracture after long-term alendronate therapy

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