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. ? ?

National Institute of Health (NIH)
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Research Project (R01)
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Orthopedics and Musculoskeletal Study Section (ORTH)
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Lester, Gayle E
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University of Pennsylvania
Internal Medicine/Medicine
Schools of Medicine
United States
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Al Mukaddam, Mona; Rajapakse, Chamith S; Bhagat, Yusuf A et al. (2014) Effects of testosterone and growth hormone on the structural and mechanical properties of bone by micro-MRI in the distal tibia of men with hypopituitarism. J Clin Endocrinol Metab 99:1236-44