Clinical Question: Do oral bisphosphonates increase the risk of atypical hip and femur fractures in postmenopausal women?

Bottom Line: Oral bisphosphonate use for 5 years or longer is significantly associated with an increased risk of atypical hip and femur fractures (subtrochanteric or femoral shaft). A previous study (JAMA 2006;296:2967-38) found little if any benefit of extended bisphosphonate use beyond 5 years in reducing the risk of typical fractures of the femoral neck or intertrochanteric region. Although this study design (case-control) is classified as weak evidence (LOE = 3b), it may be the best we have for some time. Thus, practicing clinicians should consider stopping bisphosphonates for most women after 5 years, except for those at high risk (eg, chronic steroid users). (Level of Evidence: 3b)

Reference: Park-Wyllie LY, Mamdani MM, Juurlink DN, et al. Bisphosphonate use and the risk of subtrochanteric or femoral shaft fractures in older women. JAMA 2011;305(8):783-789.

Study Design: Case-control

Funding Source: Government

Setting: Population-based

Synopsis: Current evidence on whether bisphosphonates increase the risk of subtrochanteric or femoral shaft fractures in postmenopausal women is uncertain. These investigators analyzed information obtained from multiple databases on the association between bisphosphonate use and fractures in a cohort of women in Ontario, Canada, 68 years or older, who initially started oral bisphosphonate (alendronate, risedronate, or etidronate) therapy between April 2002 and March 2008. Separate databases included information on drug prescriptions, hospitalizations, physician service claims, cancer, and basic demographic information. Cases included those women hospitalized with a subtrochanteric or femoral shaft fracture. Up to 5 women who were not hospitalized with similar fractures were matched to age and cohort entry date and served as control patients. Analyses were performed to adjust for other fracture risk factors. During the 7-year study period, 205,466 women commenced oral bisphosphonate therapy. Of these, 716 (0.35%) were hospitalized for an atypical subtrochanteric or femoral shaft fracture. The use of bisphosphonates for 5 years or longer, compared with transient or no use, was associated with a significantly increased risk of atypical hip or femur fracture (odds ratio [OR] = 2.74; 95% CI, 1.25-6.02). Among the 52,595 women using bisphosphonates for at least 5 years, a subtrochanteric or femoral shaft fracture occurred in 188 (0.36%) within 2 years. Duration of therapy of less than 5 years was not associated with an increased risk of fracture.