Bone Mineral Content and Density in the Humerus of Adult Myostatin-Deficient Mice

Myostatin (GDF-8), a member of the transforming growth factor-b superfamily of secreted growth and differentiation factors, is a negative regulator of skeletal muscle growth. We investigated the effects of increased muscle mass on bone morphology by examining bone mineral content and density in the humeri of myostatin-deficient mice. We compared the humeri of 11 mixed-gender, adult mice homozygous for the disrupted myostatin sequence with those from 11 mixed-gender, adult wild-type mice. Body mass, deltoid mass, and triceps mass were recorded from each animal and densitometric and geometric parameters were collected from the humerus using peripheral quantitative computed tomography (pQCT). Cross-sectional slices were scanned at four different positions along the humerus corresponding to 15%, 40%, 60%, and 85% of total humerus length. Results show that the myostatin- deficient mice weigh more than controls and have significantly larger triceps and deltoid muscles. The myostatin-deficient animals also have significantly (P < 0.05) higher trabecular area and trabecular bone mineral content (BMC) in the proximal humerus (15% length) and significantly (P < 0.01) higher cortical BMC, cortical area, and periosteal circumference in the region of the deltoid crest (40% length). The myostatin knockouts otherwise do not differ from controls in cortical BMC. Moreover, experimental and control mice do not differ significantly from one another in cortical bone mineral density (BMD) at any of the sites examined. These results suggest that the effects of increased muscle mass on the mouse humerus are localized to regions where muscles attach; furthermore, these effects include increased mineral content of both trabecular and cortical bone.