Risk Of Atypical Femoral Fractures Research Articles

Oral bisphosphonates are associated with increased risk of subtrochanteric and diaphyseal fractures in elderly women: a nested case–control study

ObjectivesTo evaluate the association between bisphosphonate use and the risk of atypical femoral fractures among women aged 65 or older.DesignNested case–control study.SettingGeneral practice research database in Spain.ExposuresUse of oral bisphosphonates...

BP use is associated with an increased risk of atypical femoral fractures

BP use is associated with an increased risk of atypical femoral fractures

Amgen Canada Inc. is warning of the risk of atypical femoral fracture associated with use of the osteoporosis treatment, Prolia [denosumab

Amgen Canada Inc. is warning of the risk of atypical femoral fracture associated with use of the osteoporosis treatment, Prolia [denosumab

Atypical Femoral Fracture Risk in Patients Treated With Bisphosphonates

There is increasing evidence that the use of bisphosphonates to prevent osteoporotic fractures, particularly long-term use, is associated with an increased risk of unusual fractures of the proximal femur. Numerous case reports of these “atypical” fractures of the femur among bisphosphonate-treated women have appeared over the last 5 years or more.1,2 A case definition for atypical femur fractures has now been proposed3 that includes subtrochanteric (below the lesser trochanter) or diaphyseal (above the distal metaphysis) location, transverse or nearly transverse “chalklike” fracture line (as opposed to the more typical spiral or comminuted fractures), and paucity of trauma. Additional features may include the presence of prodromal thigh pain, bilateral involvement, cortical thickening, and the presence of other selected diseases (such as rheumatoid arthritis or diabetes) or medication use (such as corticosteroids or proton pump inhibitors). Some reports, but certainly not all, suggest marked suppression of bone turnover as assessed by bone turnover markers and iliac crest histomorphometry.1 Even if causally related, these atypical fractures must be quite rare among osteoporotic women treated with bisphosphonates, as a recent pooled analysis of 3 large clinical trials (FIT, FLEX, and HORIZON) with up to 10 years of follow-up4 found that all types of subtrochanteric and diaphyseal fractures were infrequent and similar among placebo- and bisphospho-nate-treated women. Although these findings are reassuring, important limitations were that relatively few women received more than 5 years of bisphosphonate treatment, information on atypical features was not specifically collected, and only radiographic reports were reviewed. Clearly, because atypical subtrochanteric fractures occur infrequently, they are unlikely to be easily studied in randomized trials, and other study designs will be necessary.

Bisphosphonate Use Raises Risk for Atypical Femoral Fracture

Bisphosphonate use may have a paradoxical effect of adversely affecting bone architecture, thereby raising risk for atypical femoral fractures. In this

Atypical femur fractures among breast cancer and multiple myeloma patients receiving intravenous bisphosphonate therapy

PurposeAtypical femur fractures represent a potential complication of chronic oral bisphosphonate therapy in women with osteoporosis, but the risk of atypical femur fractures among cancer patients receiving intravenous bisphosphonates at higher cumulative doses remains unclear. We examined femur fractures occurring in cancer patients treated with intravenous bisphosphonates (IVBP) to determine whether a subset may be atypical fractures. MethodsBetween 2005 and 2010, we identified patients with known IVBP therapy for multiple myeloma or metastatic breast cancer, who subsequently sustained a femur fracture based on hospitalization, oncology, pharmacy and chemotherapy visit records. Radiographs were examined by an orthopedic surgeon to determine anatomic fracture site and pattern. An atypical fracture was defined as a transverse or short oblique fracture occurring below the lesser trochanter with evidence of focal hypertrophy of the lateral cortex and absence of biopsy-proven malignancy or radiation therapy at the fracture site. ResultsA total of 62 patients with breast cancer (N=39) or multiple myeloma (N=23) with femur fracture and prior IVBP treatment for bone malignancy were identified. There were 30 proximal hip, 18 subtrochanteric and 14 femoral shaft fractures. Intraoperative bone samples were sent in 29 of 58 fracture cases undergoing operative repair, with 76% positive for malignancy. Six cases (4 breast cancer, 2 multiple myeloma) of atypical femur fracture were identified, two with negative intraoperative pathology and four with no bone biopsy samples sent. Five of the six patients with atypical fracture had bilateral femur findings, including two with transverse fracture in the contralateral femur and three with focal hypertrophy of the contralateral cortex. Two atypical fracture cases also experienced osteonecrosis of the jaw compared to 3 in the remaining cohort (33% vs. 5%, p=0.07). Patients with atypical fracture received more IVBP (median 55 vs. 15 doses) and zoledronic acid (32 vs. 12 doses) and had longer treatment duration (median 5.9 vs. 1.6years) compared to patients without atypical fracture (all p≤0.01). ConclusionsAmong 62 patients who received IVBP for skeletal malignancy and experienced a femur fracture, we identified six cases of atypical fracture. While fractures in this population are often assumed to be pathologic, prospective studies investigating fracture pattern, microscopic bone pathology and pharmacologic exposures should be conducted to further examine the association of IVBP and atypical femur fractures.

Hip and Subtrochanteric or Diaphyseal Femoral Fractures in Alendronate Users: A 10-Year, Nationwide Retrospective Cohort Study in Taiwanese Women

Background A link between the use of alendronate and atypical diaphyseal femoral fracture has been suggested. Objective The goal of this study was to evaluate the benefits of alendronate in preventing rehospitalization due to hip fractures and whether its use increases risk of hospitalization for atypical diaphyseal femoral fractures in Taiwan. Methods Using Taiwan's National Health Insurance database, we identified women with osteoporosis with a first-ever hospitalization for vertebral or hip fractures between 2001 and 2007, which consisted of all patients receiving alendronate, raloxifene, calcitonin salmon, or teriparatide after the index fracture hospitalization. Data of untreated women were obtained as the untreated cohort. Study outcomes were defined as a rehospitalization due to hip fracture or a new hospitalization for subtrochanteric or diaphyseal femoral fracture. Results Among 11,278 women identified (mean age, 77 years), 2425 (21.5%) received alendronate, 2694 (23.9%) received other antiosteoporosis drugs, and 6159 (54.6%) were untreated. Patients in each group were comparable in fracture history and major comorbidities; untreated patients were more likely to have stroke (11.2%; P = 0.01) and those treated with alendronate were more likely to have a history of hyperlipidemia (16.2%; P = 0.03). Compared with the untreated patient cohort, our analysis suggested that patients prescribed alendronate were associated with decreased risk of rehospitalization due to hip fracture (hazard ratio = 0.67 [95% CI, 0.54–0.82]). Neither patients prescribed alendronate, nor those prescribed other antiosteoporosis drugs, differed significantly from the untreated patient cohort in terms of risk of hospitalization for atypical femoral fracture (adjusted hazard ratios = 0.77 and 0.49 [95% CI, 0.40–1.47 and 0.22–1.12], respectively). Consistent with these data, short- or long-term alendronate use was not found to be significantly associated with higher risk of atypical femoral fractures. Conclusions This study in Taiwanese patients suggests that alendronate use was associated with a reduction in risk of rehospitalization due to hip fracture. We did not find a significant association between alendronate use and risk of hospitalization for atypical femoral fracture.