Targeting Transforming Growth Factor Beta to Enhance the Fracture Resistance of Bone

Because aging can lower the fracture resistance of bone in ways that are independent of bone mass, the present project investigated the possibility that transforming growth factor TGF-Beta inhibition could improve multiple measurements of fracture resistance in growing, mature adult, and old rodents. TGF-Beta inhibition was achieved with a neutralizing antibody known as 1D11. When administered to growing mice for 4 weeks 13 to 17 weeks of age, 1D11 substantially increased trabecular bone volume fraction. Moreover, treatment-related improvements in trabecular architecture and tissue mineral density translated to stronger vertebral bodies. When administered to adult 6 months and old rats 22 months for 6 weeks, 1D11 did not have an appreciable effect on trabecular bone. As another example of differential effects of 1D11 between mice and rats, treatment increased the estimated material strength of cortical bone in mice while it increased the structural strength of cortical bone in old rats with no effects on bone in adult rats. In comparison to control antibody treatment, 1D11 also increased the fracture toughness of bone from growing mice and old rats. These effects appear to be independent of bone mass, and identifying the cause e.g., changes in collagen crosslinking is the next step.