Increased formation and decreased resorption of bone in mice with elevatedvitamin D receptor in mature cells of the osteoblastic lineage

The microarchitecture of bone is regulated by complex interactions between the bone-forming and resorbing cells, and several compounds regulate both a ctions. For example, vitamin D, which is required for bone mineralization, also stimulates bone resorption. Transgenic mice overexpressing the vitamin D receptor solely in mature cells of the osteoblastic bone-forming lineage were generated to test the potential therapeutic value of shifting the bal ance of vitamin D activity in favor of bone formation. Cortical bone was 5% wider and 15% stronger in these mice due to a doubling of periosteal miner al apposition rate without altered body weight or calcium homeostatic hormo ne levels. A 20% increase in trabecular bone volume in transgenic vertebrae was also observed, unexpectedly associated with a 30% reduction in resorpt ion surface rather than greater bone formation. These findings indicate ana bolic vitamin D activity in bone and identify a previously unknown pathway from mature osteoblastic cells to inhibit osteoclastic bone resorption, cou nterbalancing the known stimulatory action through immature osteoblastic ce lls. A therapeutic approach that both stimulates cortical anabolic and inhi bits trabecular resorptive pathways would be ideal for treatment of osteopo rosis and other osteopenic disorders.