Increased bone mineral density in the femora of GDF8 knockout mice

GDF8 (myostatin), a member of the transforming growth factor (TGF)-beta superfamily of secreted growth and differentiation factors, is a negative regulator of skeletal muscle growth. GDF8 knockout mice have approximately twice the skeletal muscle mass of normal mice. The effects of increased muscle mass on bone modeling were investigated by examining bone mineral content (BMC) and bone mineral density (BMD) in the femora of female GDF8 knockout mice. Dual-energy X-ray absorptiometry (DEXA) densitometry was used to measure whole-femur BMC and BMD, and pQCT densitometry was used to calculate BMC and BMD from cross-sections taken at two different locations: the midshaft and the distal metaphysis. The DEXA results show that the knockout mice have significantly greater femoral BMD than normal mice. The peripheral quantitative computed tomography (pQCT) data indicate that the GDF8 knockout mice have approximately 10% greater cortical BMC (P =.01) at the midshaft and over 20% greater cortical BMC at the metaphysis (P <.001). Likewise, knockouts show approximately 10% greater cortical thickness (P <.001) and significantly greater cortical BMD (P <.001) at both locations. These results suggest that inhibitors of GDF8 function may be useful pharmacological agents for increasing both muscle mass and BMD.