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，每一种替代都会增加骨矿物质密度，但在多大程度上（如果有的话）替代会改善骨质量尚不清楚。基于磁共振的骨结构分析技术的最新发展允许对骨的几个结构参数进行无创的纵向评估，这些参数对骨质量有重要贡献，包括那些反映骨小梁网络完整性的结构参数。使用这些技术的初步数据表明，性腺功能低下的男性的小梁结构与性腺功能正常的男性相比大大恶化。本研究的总体目标是使用垂体功能低下导致的睾酮和生长激素联合缺乏的模型来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因为它们是受试者将缺乏的激素，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，而且它们在许多组织中的作用是附加的。我们计划选择年龄大于18岁、因垂体或下丘脑疾病而明确缺乏睾酮和生长激素且未接受治疗的男性；将他们随机分为单独接受睾酮或睾酮加生长激素两组，为期两年；并调整剂量以保持血清睾酮和IGF-1正常。在治疗0、12和24个月时通过磁共振评估胫骨远端小梁结构。磁共振参数包括骨体积分数、骨小梁厚度和反映骨小梁网络完整性的结构参数。通过DEXA评估脊柱和髋部骨密度，通过外周QCT评估胫骨皮质厚度和密度。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在外，入组的受试者将在整个研究过程中对这些疾病进行监测。本研究的潜在意义在于，它应该证明(1)已知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，还会改善骨小梁网络的完整性，这对骨质量更重要；(2)基于磁共振的骨结构分析的价值，这可能会改变未来骨质量的评估方式。

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.