Femur Fracture Outcomes Associated with Bisphosphonate Use

描述(申请人提供)：骨质疏松症是一种在老年绝经后妇女中非常普遍的疾病，预计每2名白人妇女中就有1人在有生之年经历骨质疏松性骨折-这种风险通过骨质疏松症治疗大大降低。在临床实践中，口服双膦酸类药物被认为是治疗骨质疏松症的主要疗法之一，基于强有力的随机临床试验证据表明，在治疗骨质疏松症的过程中，髋部、脊柱和非椎体临床骨折的风险显著降低。 头3-5年的治疗。然而，关于这一初始治疗期之后的骨折结果的数据有限，最近关于接受长期双膦酸药治疗的妇女中非典型股骨骨折的报道提出了对最佳治疗时间的担忧。不典型的股骨骨折表现为股骨干的横形骨折，从股骨外侧皮质局部骨膜反应区域向内侧延伸。这些不常见的骨折被认为是由于长期抑制正常的骨重建和受损的微裂纹修复而发展起来的，在高机械应力区域，裂纹的病理性扩展不受阻碍。初步研究结果表明，接受双磷酸盐治疗的患者发生非典型股骨骨折的风险增加。此外，尽管非典型骨折的风险似乎比典型的骨质疏松性髋部骨折的风险要低得多，但随着双膦酸类药物治疗时间的延长，非典型骨折的风险会增加，而亚洲种族的女性可能会更高。这项研究将利用两个人群队列来解决两个具体目标：目标1将研究早期停止双磷酸盐治疗与启动双磷酸盐治疗的女性随后发生非典型股骨骨折的风险之间的关系。目的2将研究长期持续双膦酸类药物治疗与接受治疗至少三年的女性非典型股骨骨折风险之间的关系。这项合作调查将在加利福尼亚州凯撒永久医院内进行，将汇集接受双磷酸盐治疗的最大女性群体之一，从而可以系统地确定治疗暴露和股骨骨折结果。这项研究预计将有大量的亚洲妇女亚群，占接触双磷酸盐的妇女的15%-20%，这项研究将填补患有骨质疏松症的绝经后妇女的管理方面的重要知识空白，以及治疗结果中潜在的种族/民族差异。

DESCRIPTION (provided by applicant): Osteoporosis is a highly prevalent disorder in older postmenopausal women, with 1 in 2 women of white race expected to experience an osteoporotic fracture in her lifetime - a risk that is substantially reduced with osteoporosis therapy. In clinical practice, the oral bisphosphonate drugs are considered one of the primary therapies for osteoporosis, based on strong randomized clinical trial evidence showing a significant reduction in the risk of hip, vertebral and non-vertebral clinical fractures during the first 3-5 years of therapy. However, data are limited regarding fracture outcomes beyond this initial treatment period, and recent reports of atypical femur fracture in women receiving long-term bisphosphonate therapy have raised concerns regarding the optimal duration of treatment. The atypical femur fractures present as a transverse fracture in the femoral diaphysis extending medially from an area of localized periosteal reaction in the lateral femoral cortex. These unusual fractures are thought to develop secondary to chronic suppression of normal bone remodeling and impaired micro-crack repair, with pathologic extension of unimpeded crack progression in an area of high mechanical stress. Preliminary findings point to an increased risk of atypical femur fracture in patients receiving bisphosphonate therapy. Furthermore, while the risk of atypical fracture appears to be much lower than the risk for typical osteoporotic hip fractures, the risk of atypical fracture is increased with longer bisphosphonate treatment duration and may be much higher for women of Asian race. This study will utilize two population cohorts to address two Specific Aims: Aim 1 will examine the association of early discontinuation of bisphosphonate therapy and subsequent risk of atypical femur fracture among women who initiate bisphosphonate therapy. Aim 2 will examine the association of long-term continuation of bisphosphonate therapy and risk of atypical femur fracture among women who have been treated for at least three years. This collaborative investigation, to be conducted within Kaiser Permanente Northern and Southern California, will assemble one of the largest populations of women receiving bisphosphonate therapy for which treatment exposures and femur fracture outcomes can be systematically identified. With an anticipated large subpopulation of Asian women comprising up to 15-20% of women with bisphosphonate exposure, this study will fill an important knowledge gap in the management of postmenopausal women with osteoporosis and potential racial/ethnic disparities in treatment outcome.