Osteoporosis-Related Fractures in HIV-Infected Patients Receiving Long-Term Tenofovir Disoproxil Fumarate: An Observational Cohort Study

INTRODUCTION: Patients with HIV infection may have a higher prevalence of osteoporosis and osteopenia, as well as an increased risk of bone fracture compared with non-HIV-infected individuals. Antiretroviral therapy is thought to be one of factors associated to osteoporosis-related bone fractures. OBJECTIVE: The aim of this study was to assess the effects of long-term exposure to tenofovir disoproxil fumarate (TDF) on the cumulative risk of osteoporosis-related bone fractures in Japanese patients with HIV infection. DESIGN: This observational cohort study comprised a joint HIV-related drug survey of patients treated with TDF between April 2004 and March 2013. METHODS: Thirty-five healthcare facilities in Japan participated in the survey. The incidence of osteoporosis-related fractures was extracted from all adverse events (AEs) using standardized Medical Dictionary for Regulatory Activities queries, and used to calculate the fracture rate per 10,000 patient-years (PY). Kaplan–Meier analysis was used to estimate the cumulative probability of fracture during the study period. RESULTS: A total of 3251 patients who received TDF or TDF/emtricitabine between April 2004 and March 2013 were analyzed in this study; 93.5% of patients were male. The fracture rate was 13.5 per 10,000 PY in males and 42.2 per 10,000 PY in females. The mean age for male patients with osteoporosis-related fracture was 43.2 years, whereas it was 65.7 years in female patients. The cumulative probability of osteoporosis-related fracture increased after ≥ 5 years of TDF exposure. The rate of hip fracture (95% confidence interval) was 7.2 (3.1–14.2) per 10,000 PY. CONCLUSIONS: Among HIV-infected patients in Japan, treatment with TDF for ≥ 5 years increases the risk of bone fractures in younger men, in addition to that seen in older post-menopausal women.