The Bone Trial of the Testosterone Trial

描述（由申请人提供）：睾酮试验是一项随机、安慰剂对照的六组密切协调试验，受试者为 800 名 65 岁以上、血清睾酮水平明显较低的男性，研究睾酮治疗一年对身体功能、性功能、活力、认知、贫血和心血管风险的影响。睾酮试验已获得资助，预计将于 2010 年夏季开始招募受试者。我们建议在 200 名参加睾酮试验的男性中增加一项骨骼试验。骨骼试验的基本原理是，尽管有明确的证据表明，睾酮可以极大地改善因已知垂体或睾丸疾病而严重性腺功能减退的男性的骨小梁密度和强度，但睾酮改善睾酮缺乏程度较轻的老年男性的骨骼的证据却是模棱两可的。我们建议利用睾酮试验中男性的可用性，这些男性已被招募和筛选，发现其血清睾酮浓度明显较低，并同意参加该试验，以确定睾酮治疗是否会改善他们的骨质量。本试验的总体具体目的是检验以下假设：对于血清睾酮浓度 <275 ng/dL 的 65 岁以上男性，一年睾酮治疗比安慰剂更能改善骨质量。主要具体终点是通过定量计算机断层扫描 (QCT) 测定的脊柱体积骨矿物质密度 (vBMD)。次要终点是髋部 vBMD；通过 QCT 数据确定的有限元分析确定脊柱和髋部的骨强度和强度密度比；通过 DXA 测量腰椎、近端髋部和远端桡骨的面积 BMD；骨转换的血清标志物；和临床骨折。受试者 (200) 将从符合睾酮试验中一项试验资格的男性中招募，他们没有疾病，也没有服用已知影响骨骼的药物。他们将随机接受睾酮或安慰剂凝胶双盲治疗一年。将在基线和 12 个月时进行脊​​柱、髋部和桡骨远端的 QCT 和 DXA。将在基线、1、2、3、6 和 12 个月时测定骨标志物。临床骨折将在 3、6、9、12、18 和 24 个月时进行评估。骨骼试验的意义在于，它将是第一个评估睾酮对 65 岁以上睾酮水平低的男性体积 BMD 的影响的研究，更重要的是，评估睾酮对骨强度的影响。证明睾酮可以改善这些男性的骨强度，这将为进行更大规模、更长时间的试验提供依据，以确定睾酮治疗是否也能减少临床骨折。骨骼试验还将提供临床骨折的数据，以便为更大、更长的试验提供样本量估计。

DESCRIPTION (provided by applicant): The Testosterone Trial is a randomized, placebo-controlled group of six closely coordinated trials in 800 men >65 years old who have unequivocally low serum testosterone of the effect of testosterone treatment for one year on physical function, sexual function, vitality, cognition, anemia and cardiovascular risk. The Testosterone Trial has been funded and is expected to begin enrolling subjects in the summer of 2010. We propose adding a Bone Trial in a subset of 200 men who enroll in The Testosterone Trial. The rationale for The Bone Trial is that although the evidence is clear that testosterone greatly improves trabecular bone density and strength in men who are severely hypogonadal due to known pituitary or testicular disease, the evidence that testosterone improves bone in elderly men who have more modest degrees of testosterone deficiency is equivocal. We propose taking advantage of the availability of men in The Testosterone Trial who have been recruited and screened and found to have unequivocally low serum testosterone concentrations and have agreed to participate in this trial to determine definitively if testosterone treatment will improve their bone quality. The overall specific aim of this trial is to test the hypothesis that testosterone treatment for one year will improve bone quality more than placebo in men >65 years who have serum testosterone concentrations <275 ng/dL. The primary specific end point is volumetric bone mineral density (vBMD) of the spine by quantitated computed tomography (QCT). Secondary end points are vBMD of the hip; bone strength and strength-to-density ratio in the spine and hip by finite element analysis determined from the QCT data; areal BMD of the lumbar spine, proximal hip and distal radius by DXA; serum markers of bone turnover; and clinical fractures. Subjects (200) will be recruited from among men who have qualified for one of the trials in The Testosterone Trial and who have no diseases and are taking no medications known to affect bone. They will be randomized to receive testosterone or placebo gel double blindly for one year. QCT and DXA of the spine, hip and distal radius will be performed at baseline and 12 months. Bone markers will be determined at baseline, 1, 2, 3, 6, and 12 months. Clinical fractures will be assessed at 3, 6, 9, 12, 18 and 24 months. The significance of The Bone Trial is that it would be the first study to assess the effect of testosterone on volumetric BMD in men >65 with low testosterone and, more importantly, on bone strength. Demonstration that testosterone improves bone strength in these men would provide the rationale for a larger, longer trial to determine if testosterone treatment reduces clinical fractures as well. The Bone Trial will also provide data on clinical fractures that will allow sample size estimation for a larger, longer trial.