Combining Testosterone Therapy and Exercise to Improve Function Post Hip Fracture

髋部骨折在老年女性中很常见，可能会对她们的 保持独立。髋部骨折后临床上重要的功能下降和恢复失败 在骨折后长达一年的时间内被记录在案，即使在功能高度正常的人中也是如此 活动前的级别。女性与年龄相关的雄激素缺乏会导致肌肉质量不足， 力量和力量，在骨折前在这一患者群体中很常见，并正在加剧 之后。老年女性髋部骨折患者补充睾酮(T)的初步研究 证明了T治疗在这一人群中的可行性，并显示出瘦体重(LBM)和 与安慰剂相比，服用活性药物后的肌肉力量。运动对恢复肌肉力量的益处 髋部骨折后的身体功能已经被记录在案。然而，尚不清楚T是否会 治疗可以增强锻炼对活动能力和患者报告的功能的影响，或者是否有 观察到的益处持续到积极治疗期之后。建议的是三个小组，多中心， 随机、安慰剂对照、双盲、平行分组治疗老年脆弱女性髋部骨折临床试验 病人。将从6个临床地点招募300名女性髋部骨折患者，采用客观筛查标准 对于T缺乏(血清总睾酮水平和30 ng/dl)和身体虚弱(修改的身体表现) 测试(PPT)分数&lt；28)。这项试验将比较单独的有监督的运动训练(EX)、EX 联合T治疗(EX+T)和无EX加安慰剂T治疗(CON)，以确定增量 高龄女性髋部骨折后补充T对ET的影响接下来将进行为期6个月的干预 经过6个月的无治疗可持续阶段。主要的结果衡量标准是六分钟步行 距离(6MWD)。次要结果指标包括：1)双能x射线吸收测量法(DXA) 全身和阑尾LBM及未骨折近端骨密度的测量 股骨；2)双腿伸展时的最大骨骼肌力(1-rm)；3)客观体能 业绩衡量；和4)自我报告的日常生活活动和生活质量的业绩，包括 髋关节评分问卷(HRQ)。我们计划仔细监测睾丸激素水平，不良事件， 生化参数，以及与坚持干预措施相关的因素。 这项研究的信息有可能改变老年女性髋部骨折的治疗，这是一个问题 这导致了严重的发病率和死亡率，并对公共卫生产生了重大影响。建议数 这项研究与NIA确定针对常见老年疾病的干预措施的使命高度一致， 并改善患有多种疾病或风险因素的老年人的治疗选择。

Hip fractures are common among older women and can have a devastating impact on their ability to remain independent. A clinically important functional decline and failure to recover following a hip fracture has been documented as much as a year after the fracture, even among individuals who were functioning at high levels before the event. Age-associated androgen deficiency in women contributes to deficits in muscle mass, strength and power that are common in this patient population before the fracture, and are exacerbated afterward. A pilot study of testosterone (T) supplementation in elderly female hip fracture patients has demonstrated the feasibility of T treatment in this population, and showed gains in lean body mass (LBM) and muscle strength with active drug, compared to placebo. The benefits of exercise in restoring muscle strength and physical function after a hip fracture have been documented. However, it remains unclear whether T treatment can augment the effects of exercise on mobility and patient-reported function, or whether any observed benefits are sustained beyond the period of active treatment. Proposed is a 3-group, multi-center, randomized, placebo-controlled, double-blinded, parallel group clinical trial in frail elderly female hip fracture patients. 300 female hip fracture patients will be enrolled from 6 clinical sites, using objective screening criteria for T deficiency (serum total testosterone level < 30 ng/dl) and physical frailty (Modified Physical Performance Test (PPT) Score < 28). The trial will compare the effects of supervised exercise training (EX) alone, EX combined with T therapy (EX+T) and no EX with placebo T treatment (CON), to ascertain the incremental impact of adding T to ET in older adult women following hip fracture. The 6-month intervention will be followed by a 6-month no-treatment sustainability phase. The primary outcome measure is the Six Minute Walk Distance (6MWD). Secondary outcome measures include: 1) dual energy x-ray absorptiometry (DXA) measurements of whole body and appendicular LBM and bone mineral density of the unfractured proximal femur; 2) maximal skeletal muscle strength (1-RM) for leg extension in both limbs; 3) objective physical performance measures; and 4) self-reported performance of activities of daily living and quality of life, including the Hip Rating Questionnaire (HRQ). We plan to carefully monitor testosterone levels, adverse events, biochemical parameters, and factors related to adherence to the interventions. Information from this study has the potential to alter treatment of hip fracture in older women, a problem that contributes to significant morbidity and mortality, and has a large public health impact. The proposed study is highly aligned with NIA’s mission of identifying interventions that target common geriatric conditions, and improve treatment options for older adults with multiple morbidities or risk factors.