COMBINING TESTOSTERONE THERAPY AND EXERCISE TO IMPROVE FUNCTION POST HIP FRACTURE

描述(由申请人提供)：髋部骨折在老年妇女中很常见，可能会对她们保持独立的能力产生毁灭性的影响。髋部骨折后出现明显的功能衰退，许多患者有持续性的力量和活动能力缺陷，这损害了他们独立生活的能力。这些人在持续的支持性服务、反复受伤和住院方面的RSK很高。高危患者包括那些在骨折后阶段骨骼肌力量不足的患者。与年龄相关的雄激素缺乏导致肌肉质量和力量的缺陷，这在该患者群体中很常见。运动训练可以在一定程度上扭转骨骼肌力量和功能表现的缺陷。我们观察到老年女性髋部骨折患者有较高的睾酮缺乏率。睾酮治疗对改善虚弱老年人肌肉质量、力量和功能能力缺陷的作用尚不清楚，特别是对老年妇女。在我们R21项目的基础上进行扩展 为了证明研究的可行性，拟议的项目将开发一项前瞻性随机、双盲、安慰剂对照试验，以确定在社区居住的老年(e65岁)女性髋部骨折患者中，单独和联合接受6个月的睾酮治疗和运动训练在改善骨折后肌肉力量和身体功能方面的有效性。我们的具体目标是：1)最终确定拟议临床试验的方案(研究假设和试验设计、资格标准、研究处理细节、安全性评估、样本量、分析计划，包括中期分析计划)；2)建立研究团队并最终确定试验的协作安排(临床试验地点和相关协议)；3)制定数据管理和质量控制计划；4)制定详细的程序手册，包括建立确保跨地点程序标准化的方法，以及工作人员培训和认证计划。我们将汇聚一支具有专业知识的优秀研究团队，从事髋部骨折患者的临床试验、睾酮替代疗法、运动训练、临床试验设计、MRI和定量CT成像技术、数据分析和管理。这些努力将导致向国家老龄研究所(NIA)提交赠款申请，以测试拟议的干预措施在老年女性髋部骨折患者中的作用。拟议的临床试验也将是 首先阐明睾酮治疗结合运动训练对老年妇女髋部骨折后康复的作用，这是一个对公众健康影响很大的问题。

DESCRIPTION (provided by applicant): Hip fractures are common in elderly women and can have a devastating impact on their ability to remain independent. A significant functional decline following a hip fracture has been documented, and many patients have persistent strength and mobility deficits that impair their capacity for independent living. Such individuals are at high rsk for continued supportive services, recurrent injury, and institutionalization. High-risk patients include those with deficits in skeletal muscle strength during the post-fracture period. Age-associated androgen deficiency contributes to deficits in muscle mass and strength that are common in this patient population. Exercise training can reverse deficits in skeletal muscle strength and functional performance to a modest degree. We have observed a high rate of testosterone deficiency in elderly female hip fracture patients with physical frailty. The role of testosterone therapy for improving deficits in muscle mass, strength, and functional capacity in the frail elderly is unclear, particularly for elderly women. Expanding from our R21 project which showed study feasibility, the proposed project will develop a prospective randomized, double-blinded, placebo-controlled trial to determine, in community-dwelling elderly (e65 yrs) female hip fracture patients, the efficacy of 6 months of testosterone therapy and exercise training, alone and in combination, at improving muscle strength and physical function after the fracture event. Our specific aims are to: 1) Finalize the protocol for the proposed clinical trial (study hypothese and experimental design, eligibility criteria, details of study treatments, safety assessments, sample size, analysis plan, including plans for an interim analysis); 2) Establish the research team and finalize the collaborative arrangements for the trial (clinical trial sites and related agreements); 3) Develop a plan for data management and quality control; 4) Develop a detailed manual of procedures including establishing the means to assure standardization of procedures across sites, and plans for staff training and certification. We will bring together an outstandin team of investigators with expertise conducting clinical trials of hip fracture patients, testosterone replacement therapy, exercise training, clinical trial design, MRI and Quantitative CT imaging techniques, data analysis and management. These efforts will lead to submission of a grant application to the National Institute on Aging (NIA) to test the role for the proposed interventions in elderly female hip fracture patients. The proposed clinical trial will also be the first to elucidate the role of testosterone therapy combined with exercise training for improving recovery in elderly women after hip fracture, which is a problem with a large public health impact.