Will Testosterone /Growth Hormone Improve Bone Structure

描述（由申请人提供）：睾酮和生长激素的缺乏都会导致男性骨质疏松症，每种激素的替代都会增加骨密度，但尚不清楚替代会在多大程度上改善骨质量。最近发展的磁共振为基础的技术，骨结构分析允许非侵入性，纵向评估的几个结构参数的骨，骨质量的重要贡献，包括那些反映的小梁网络的完整性。使用这些技术的初步数据表明，性腺功能减退的男性的小梁结构大大恶化相匹配的性腺功能正常的男性。拟议研究的总体目标是使用由于垂体功能减退症导致的睾酮和生长激素联合缺乏的模型，以确定睾酮和生长激素的替代是否会改善有助于其质量的骨结构参数。使用这两种激素的理由不仅是它们是受试者缺乏的激素，而且它们都是合成代谢的，不像大多数其他影响骨骼的药物，它们在许多组织中的作用是累加的。我们计划选择18岁以上的男性，由于垂体或下丘脑疾病而明显缺乏睾酮和生长激素，并且未接受治疗;随机接受睾酮单独或睾酮加生长激素两年;并调整剂量以保持血清睾酮和IGF-1正常。将在治疗0、12和24个月时通过磁共振评估胫骨远端的骨小梁结构。磁共振参数将包括骨体积分数、骨小梁厚度和反映骨小梁网络完整性的结构参数。将通过DEXA评估脊柱和髋关节的骨密度，通过外周QCT评估胫骨的皮质厚度和密度。患有可能因睾酮或生长激素替代而加重的疾病的男性将被排除，入组的受试者将在整个研究期间接受这些疾病的监测。本研究的潜在意义在于，它应证明（1）已知可增加骨密度的合成代谢激素是否不仅会增加骨体积分数和骨小梁厚度，而且还会改善骨小梁网络的完整性，这对骨质量甚至更重要;以及（2）基于磁共振的骨结构分析的价值，这可能会改变未来评估骨质量的方式。

DESCRIPTION (provided by applicant): Deficiencies of testosterone and growth hormone both cause osteoporosis in men, and replacement with each increases bone mineral density, but it is not known to what extent, if any, replacement improves bone quality. The recent development of magnetic resonance-based techniques for the structural analysis of bone permits the noninvasive, longitudinal assessment of several structural parameters of bone that contribute importantly to bone quality, including those that reflect the integrity of the trabecular network. Preliminary data using these techniques demonstrate that the trabecular architecture of hypogonadal men is greatly deteriorated compared to that of matched eugonadal men. The overall goal of the proposed study is to use the model of combined testosterone and growth hormone deficiencies due to hypopituitarism to determine if replacement of testosterone and growth hormone will improve structural parameters of bone that contribute to Its quality. The rationale for the use of these two hormones is not only that they are the hormones the subjects will be lacking, but also that they are both anabolic, unlike most other agents that affect bone, and that their effects in many tissues are additive. We plan to select men who are greater than 18 yrs old, unequivocally deficient in testosterone and growth hormone due to pituitary or hypothalamic disease and untreated for both; randomize them to receive testosterone alone or testosterone plus growth hormone for two years; and adjust the doses to keep the serum testosterone and IGF-1 normal. Trabecular structure of the distal tibia will be assessed by magnetic resonance at 0, 12, and 24 months of treatment. The magnetic resonance parameters will include bone volume fraction, trabecular thickness, and architectural parameters that reflect the integrity of the trabecular network. Bone density of the spine and hip will be assessed by DEXA and cortical thickness and density of the tibia by peripheral QCT. Men will be excluded who have diseases that could be exacerbated by testosterone or growth hormone replacement, and subjects who enroll will be monitored for these conditions throughout the study. The potential significance of this study is that it should demonstrate (1) if anabolic hormones known to increase bone density will increase not only bone volume fraction and trabecular thickness, but will also improve the integrity of the trabecular network, which would be of even greater importance for bone quality; and (2) the value of magnetic resonance-based analysis of bone structure, which could change how bone quality is evaluated in the future.