Mona Al Mukaddam1, Chamith S Rajapakse, Yusuf A Bhagat, Felix W Wehrli, Wensheng Guo, Helen Peachey, Shane O LeBeau, Babette S Zemel, Christina Wang, Ronald S Swerdloff, Shiv C Kapoor, Peter J Snyder. 1. Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine (M.A.M., H.P., S.O.L., P.J.S.); Laboratory of Structural NMR Imaging, Department of Radiology (C.S.R., Y.A.B., F.W.W.), Department of Biostatistics and Epidemiology (W.G.), and the Clinical and Translational Research Center (S.C.K.), Raymond and Ruth Perelman School of Medicine, University of Pennsylvania; and the Division of Gastroenterology, Hepatology, and Nutrition (B.S.Z.), The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104; and Division of Endocrinology and Metabolism (C.W., R.S.S.), Harbor-University of California at Los Angeles Medical Center and Los Angeles Biomedical Research Institute, Torrance, California 90509.
Abstract
CONTEXT: Severe deficiencies of testosterone (T) and GH are associated with low bone mineral density (BMD) and increased fracture risk. Replacement of T in hypogonadal men improves several bone parameters. Replacement of GH in GH-deficient men improves BMD. OBJECTIVE: Our objective was to determine whether T and GH treatment together improves the structural and mechanical parameters of bone more than T alone in men with hypopituitarism. DESIGN AND SUBJECTS: This randomized, prospective, 2-year study included 32 men with severe deficiencies of T and GH due to panhypopituitarism. INTERVENTION: Subjects were randomized to receive T alone (n = 15) or T and GH (n = 17) for 2 years. MAIN OUTCOME MEASURES: We evaluated magnetic resonance microimaging-derived structural (bone volume fraction [BVF] and trabecular thickness) and mechanical (axial stiffness [AS], a measure of bone strength) properties of the distal tibia at baseline and after 1 and 2 years of treatment. RESULTS: Treatment with T and GH did not affect BVF, thickness, or AS differently from T alone. T treatment in all subjects for 2 years increased trabecular BVF by 9.6% (P < .0001), trabecular thickness by 2.6% (P < .001), and trabecular AS by 9.8% (P < .001). In contrast, testosterone treatment in all subjects significantly increased cortical thickness by 2.4% (P < .01) but decreased cortical BVF by -4.7% (P < .01) and cortical AS by -6.9% (P < .01). CONCLUSION: Combined T and GH treatment of men with hypopituitarism for 2 years did not improve the measured structural or mechanical parameters of the distal tibia more than T alone. However, testosterone significantly increased the structural and mechanical properties of trabecular bone but decreased most of these properties of cortical bone, illustrating the potential importance of assessing trabecular and cortical bone separately in future studies of the effect of testosterone on bone.
RCT Entities:
CONTEXT: Severe deficiencies of testosterone (T) and GH are associated with low bone mineral density (BMD) and increased fracture risk. Replacement of T in hypogonadal men improves several bone parameters. Replacement of GH in GH-deficientmen improves BMD. OBJECTIVE: Our objective was to determine whether T and GH treatment together improves the structural and mechanical parameters of bone more than T alone in men with hypopituitarism. DESIGN AND SUBJECTS: This randomized, prospective, 2-year study included 32 men with severe deficiencies of T and GH due to panhypopituitarism. INTERVENTION: Subjects were randomized to receive T alone (n = 15) or T and GH (n = 17) for 2 years. MAIN OUTCOME MEASURES: We evaluated magnetic resonance microimaging-derived structural (bone volume fraction [BVF] and trabecular thickness) and mechanical (axial stiffness [AS], a measure of bone strength) properties of the distal tibia at baseline and after 1 and 2 years of treatment. RESULTS: Treatment with T and GH did not affect BVF, thickness, or AS differently from T alone. T treatment in all subjects for 2 years increased trabecular BVF by 9.6% (P < .0001), trabecular thickness by 2.6% (P < .001), and trabecular AS by 9.8% (P < .001). In contrast, testosterone treatment in all subjects significantly increased cortical thickness by 2.4% (P < .01) but decreased cortical BVF by -4.7% (P < .01) and cortical AS by -6.9% (P < .01). CONCLUSION: Combined T and GH treatment of men with hypopituitarism for 2 years did not improve the measured structural or mechanical parameters of the distal tibia more than T alone. However, testosterone significantly increased the structural and mechanical properties of trabecular bone but decreased most of these properties of cortical bone, illustrating the potential importance of assessing trabecular and cortical bone separately in future studies of the effect of testosterone on bone.
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