Pharmaceutical Division, Drug Safety and Risk Management Department, Japan Tobacco Inc., Tokyo, Japan.
Center for AIDS Research, Kumamoto University, Kumamoto, Japan.
Drug Saf. 2018 Sep;41(9):843-848. doi: 10.1007/s40264-018-0665-z.
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.
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.
This observational cohort study comprised a joint HIV-related drug survey of patients treated with TDF between April 2004 and March 2013.
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.
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.
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.
与未感染 HIV 的个体相比，HIV 感染者可能患有更高的骨质疏松症和骨量减少症患病率，以及更高的骨折风险。抗逆转录病毒疗法被认为是与骨质疏松症相关的骨折的相关因素之一。
本研究旨在评估长期使用富马酸替诺福韦二吡呋酯（TDF）对日本 HIV 感染者骨质疏松症相关骨折累积风险的影响。
本观察性队列研究包括 2004 年 4 月至 2013 年 3 月期间接受 TDF 治疗的 HIV 相关药物联合调查。
日本 35 家医疗机构参与了该调查。使用标准化的监管活动医学词典查询从所有不良事件（AE）中提取骨质疏松性骨折的发病情况，并用于计算每 10000 患者年（PY）的骨折率。Kaplan-Meier 分析用于估计研究期间骨折的累积概率。
本研究共分析了 2004 年 4 月至 2013 年 3 月期间接受 TDF 或 TDF/恩曲他滨治疗的 3251 例患者；93.5%的患者为男性。男性的骨折率为每 10000PY13.5 例，女性为每 10000PY42.2 例。男性骨质疏松性骨折患者的平均年龄为 43.2 岁，而女性患者为 65.7 岁。骨质疏松性骨折的累积概率在 TDF 暴露后≥5 年增加。髋部骨折（95%置信区间）的发生率为每 10000PY7.2（3.1-14.2）例。
在日本 HIV 感染者中，TDF 治疗≥5 年除了增加老年绝经后妇女的骨折风险外，还会增加年轻男性的骨折风险。
