The Epidemiology of Metatarsal Fractures Among Older Females With Bisphosphonate Exposure

Bisphosphonates (BP) are used to treat osteoporosis, although rare atypical femur fractures have occurred with long-term exposure, especially among Asians. Metatarsal fractures have also been reported with atypical femur fracture. We examined the epidemiology of metatarsal fractures among 48,390 females aged ≥50 years who initiated oral BP and were followed for a median 7.7 years, including 68 females who experienced an atypical femur fracture. Incident metatarsal fractures after BP initiation were identified by clinical diagnoses and validated by record review. The association of BP, clinical risk factors, race/ethnicity, and metatarsal fracture was examined by using Cox proportional hazard analyses. Among 1123 females with incident metatarsal fracture, 61.0% had an isolated fifth metatarsal fracture. The incidence of metatarsal fracture was 312 per 100,000 person-years of follow-up and was substantially lower for Asians. The adjusted relative rate for metatarsal fractures was 0.5 (95% confidence interval 0.4 to 0.6) for Asians compared with whites. Younger age, prior fracture, other risk factors, and current BP were associated with an increased relative rate of metatarsal fracture, but BP duration was not. Females with atypical femur fracture were not more likely to experience metatarsal fracture (2.9% versus 2.3%, p = .7), but only 68 females had an atypical fracture and stress fracture of the metatarsals was not examined. Except for age, the demographic profile for metatarsal fracture after initiating BP was similar to that for osteoporotic fracture, with Asians at a much lower risk. Although metatarsal fractures were not associated with BP duration or atypical femur fracture, the subset of metatarsal stress fractures was not specifically examined.