Will Testosterone /Growth Hormone Improve Bone Structure

描述(申请人提供)：睾丸激素和生长激素的缺乏都会导致男性的骨质疏松症，两者的替代都会增加骨密度，但尚不清楚替代疗法在多大程度上改善了骨质量。最近基于磁共振的骨结构分析技术的发展使得对骨的几个结构参数进行非侵入性的纵向评估成为可能，这些结构参数对骨质量有重要影响，包括那些反映骨小梁网络完整性的参数。使用这些技术的初步数据显示，与匹配的优性腺男性相比，性腺功能低下的男性的骨小梁结构严重恶化。这项拟议研究的总体目标是使用睾酮和生长激素联合缺乏的模型来确定替代睾酮和生长激素是否会改善骨的结构参数，从而提高其质量。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因素，而且它们在许多组织中的作用是相加的。我们计划选择18岁以上、由于脑下或下丘脑疾病而明确缺乏睾酮和生长激素且未对两者进行治疗的男性；随机将他们分为单独接受睾酮治疗或睾酮加生长激素治疗两年；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，将通过磁共振对胫骨远端的小梁结构进行评估。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。脊柱和髋部的骨密度将通过DEXA进行评估，胫骨的皮质厚度和密度将通过外周QCT进行评估。那些患有可能会因睾酮或生长激素替代而恶化的疾病的男性将被排除在外，在整个研究过程中，将对登记的受试者进行这些情况的监测。这项研究的潜在意义是，它应该证明(1)已知的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，这对骨质量将更加重要；(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.