EXERCISE AND TESTOSTERONE THERAPY AFTER HIP FRACTURE

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。研究设计概述：本研究的目的是评估老年人体弱髋部骨折患者，运动训练联合睾酮治疗对骨量、肌肉力量和功能能力、骨密度、生活质量和ADL表现自我报告的影响。我们将利用华盛顿大学（WU）老年病学和老年学部门，普通临床研究中心和物理治疗项目目前可用的许多设施。88名65岁及以上的社区髋部骨折患者将从地区医院和家庭护理项目中招募，参加一项随机、双盲、安慰剂对照的运动训练和睾酮治疗试验。参与者将在完成标准物理治疗（骨折后12-16周）后入组，因为在骨折后立即入组是不可行的，与标准护理实践相冲突，并可能引入更大的风险。所有参与者都将完成一项运动训练计划，包括2个月的柔韧性、平衡、步行和轻度阻力训练，然后是4个月的渐进式阻力训练。参与者将被随机分配服用1%外用凝胶形式的睾丸激素，或相同的安慰剂凝胶，为期6个月。结果测量将在基线和干预后2个月和6个月获得。主要研究结果测量将是大腿肌肉横截质量（通过1H-MRI）、DXA测量的总瘦体重、骨骼肌力量测量和客观体能测试的总分。第二天的结果测量将是骨密度（BMD，通过DXA），平衡测量，步态，峰值有氧能力，ADLs表现的自我报告，情绪和生活质量。运动训练两组设计的基本原理：有些人可能会认为我们应该采用四组设计来评估睾酮治疗和运动训练的独立效果，或者用家庭运动项目来评估睾酮。在这个阶段，四组试验的招募需求是不可行的，可能需要一个多中心试验。我们建议评估睾酮与运动结合的效果，因为我们正在进行的研究的初步数据表明，尽管运动训练在扭转髋部骨折患者的身体损伤方面优于家庭运动，但许多受试者仍然虚弱。可能需要采用综合方法来最大限度地改善肌肉质量和力量以及相关的身体损伤，并减少持续残疾的风险。来自男性睾酮研究的数据表明，雄激素疗法与运动训练相结合，对肌肉力量和身体成分有叠加效应。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Overview of Research Design: The purposes of this study are to evaluate, in frail elderly hip fracture patients, the effects of exercise training combined with testosterone therapy on measures of skeletal mass, muscle strength and functional capacity, bone mineral density, quality of life, and self-report of ADL performance. We will utilize many of the facilities currently available through the Washington University (WU) Division of Geriatrics and Gerontology, General Clinical Research Center, and the Program in Physical Theray. Eighty-eight community-dwelling post-hip fracture patients aged 65 and over will be recruited from area hospitals and home care programs to participate in a randomized, double-blind, placebo-controlled trial of exercise training and testosterone therapy. Participants will enroll in the study upon completion of standard physical therapy (12-16 weeks post fracture) because enrollment during the immediate post fracture period is not feasible, conflicts with standard care practicec, and may introduce greater risks. All participants will perform an exercise-training program that will consist of 2 months of flexibility, balance, walking and light resistance exercises, followed by 4 months of progressive resistance training. Participants will be randomly assigned to take testosterone in the forma of a 1% topical gel, or an identical placebo gel, for 6 months. Outcome measurements will be obtained at baseline and after 2 and 6 months of the intervention. The primary study outcome measures will be thigh muscle cross-sectional mass (by 1H-MRI), total lean body mass as measured by DXA, measures of skeletal muscle strength, and total score for an objective Physical Performance Test. Seconday outcome meausres will be bone mineral density (BMD, by DXA), measurements of balance, gait, peak aerobic power, self-report of performance of ADLs, mood, and quality of life. Rationale for a 2-group design with exercise training: Some may argue that we should employ a 4-group design for this trial in order to evaluate the independent effects of testosterone therapy and exercise training, or evaluate testosterone with a home exercise program. The recruitment demands of a 4-group trial are not feasible at this stage, and would probably require a multi-center trial. We are proposing to evaluate the effects of testosterone combined with exercise because preliminary data from our ongoing study suggest that although exercise training is superior to home exercise in reversing physical impairments in hip fracture patients, many subjects remain frail. A combined approach may be required to achieve maximal improvements in muscle mass and strenght and related physical impairments, and to reduce the risk of persistant disability. Data from studies of testosterone in men suggest that androgen therapy combined wtih exercise training has additive effects on muscle strength and body composition.