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

Abstract

IntroductionPatients 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.ObjectiveThe 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.DesignThis observational cohort study comprised a joint HIV-related drug survey of patients treated with TDF between April 2004 and March 2013.MethodsThirty-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.ResultsA 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.ConclusionsAmong 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.

Timing, Dosage, and Adherence of Antiretroviral Therapy and Risk of Osteoporosis in Patients With Human Immunodeficiency Virus Infection in Taiwan: A Nested Case-Control Study

“…Bone mineral density screening has been suggested for male patients with HIV infection older than 50 years and in postmenopausal women (Aberg et al, 2014;Gonciulea et al, 2017). In agreement with our results, previous study findings reveal that bone loss is observed in patients with HIV infection who receive ART (Mccomsey et al, 2008;Duvivier et al, 2009;Van Vonderen et al, 2009;Haskelberg et al, 2012;Grant et al, 2016;Hoy et al, 2017;Komatsu et al, 2018).…”

“…Our results demonstrated that patients receiving NRTIcontaining regimen had a higher risk of osteoporosis. Studies have reported that NRTI-containing regimens, including zidovudine-lamivudine combination therapy and tenofovir monotherapies, induce osteoporosis or osteoporotic fractures (Van Vonderen et al, 2009;Haskelberg et al, 2012;Grant et al, 2016;Komatsu et al, 2018). Furthermore, our study showed that patients receiving zidovudine-lamivudine combination, lamivudine-abacavir combination, and abacavir had a higher risk of osteoporosis.…”

Sex Differences in Non-AIDS Comorbidities Among People With Human Immunodeficiency Virus

“…ART-exposed WWH vs MWH are at significantly greater risk of osteoporotic fracture [ 32 ]. Among ART-naive PWH initiating TDF, WWH had a 3 times greater fracture rate than MWH, and first osteoporotic fracture occurred sooner among women than men (123 vs 1438 days, respectively) [ 32 ].…”

“…ART-exposed WWH vs MWH are at significantly greater risk of osteoporotic fracture [ 32 ]. Among ART-naive PWH initiating TDF, WWH had a 3 times greater fracture rate than MWH, and first osteoporotic fracture occurred sooner among women than men (123 vs 1438 days, respectively) [ 32 ]. Another study including adult PWH showed that while MWH had a 1.5 times higher incident fracture rate compared with WWH from ages 36 to 46 years, the difference by sex diminished in older age groups [ 33 ].…”

Bone Diseases in Patients with Chronic Liver Disease

“…Loss of BMD is one of the major side effects that have been observed since its development [155]. The relationship between bone diseases (osteoporosis and fracture) and TDF has been well documented in several clinical studies of patients co-infected with HIV and treated with HBV therapy [156]. The TDF-induced decrease in BMD is mainly observed in the hip and spine [157].…”