Femur Fracture Outcomes Associated with Bisphosphonate Use

与双磷酸盐使用相关的股骨骨折结果

• 批准号: 8818973
• 负责人: Joan C Lo
• 金额: $ 49.16万
• 依托单位: KAISER FOUNDATION RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-01-15 至 2018-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8818973
• 关键词: Address; Age; Area; Asians; Benefits and Risks; California; Caucasians; Chronic; Clinical; Country; Data; Diaphyses; Disease; Event; Female; Femoral Fractures; Fracture; Health Planning; Hip Fractures; Hip region structure; Image; Innate Bone Remodeling; Investigation; Knowledge; Lateral; Mechanical Stress; Older Population; Oral; Osteoporosis; Outcome; Pathologic; Patients; Pharmaceutical Preparations; Pharmacy facility; Population; Postmenopause; Race; Randomized Clinical Trials; Reaction; Reporting; Risk; Risk Factors; Secondary to; Spinal Fractures; Stress Fractures; Subgroup; System; Treatment outcome; Woman; adverse outcome; base; bisphosphonate; clinical practice; cohort; digital; experience; follow-up; health care delivery; interest; member; older women; osteoporosis with pathological fracture; patient population; population based; public health relevance; racial and ethnic disparities; racial/ethnic difference; repaired; spine bone structure; treatment duration

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.

描述（由申请人提供）：骨质疏松症是老年绝经后女性中非常普遍的疾病，预计有二分之一的白人女性在其一生中会经历骨质疏松性骨折 - 通过骨质疏松症治疗可大大降低这种风险。在临床实践中，口服双膦酸盐药物被认为是骨质疏松症的主要治疗方法之一，基于强有力的随机临床试验证据表明，口服双膦酸盐药物在治疗期间可显着降低髋部、椎体和非椎体临床骨折的风险。 治疗的前 3-5 年。然而，关于初始治疗期之后骨折结果的数据有限，并且最近关于接受长期双磷酸盐治疗的女性非典型股骨骨折的报告引起了人们对最佳治疗持续时间的担忧。非典型股骨骨折表现为股骨骨干中的横向骨折，从股骨外侧皮质的局部骨膜反应区域向内侧延伸。这些不寻常的骨折被认为是继发于正常骨重塑的长期抑制和微裂纹修复受损，在高机械应力区域中裂纹进展不受阻碍的病理扩展。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，虽然非典型骨折的风险似乎远低于典型骨质疏松性髋部骨折的风险，但随着双磷酸盐治疗持续时间的延长，非典型骨折的风险会增加，并且对于亚洲种族女性来说，非典型骨折的风险可能要高得多。本研究将利用两个人群队列来实现两个具体目标：目标 1 将检查开始双磷酸盐治疗的女性中早期停止双磷酸盐治疗与随后发生非典型股骨骨折的风险之间的关系。目标 2 将研究长期持续双磷酸盐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。这项合作调查将在北加州和南加州凯撒医疗机构内进行，将汇集接受双磷酸盐治疗的最大女性群体之一，可以系统地确定治疗暴露和股骨骨折结果。预计亚洲女性群体中将有高达 15-20% 的双膦酸盐暴露女性，这项研究将填补绝经后女性骨质疏松症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。