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Increased formation and decreased resorption of bone in mice with elevated vitamin 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 actions. 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 balance 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 mineral apposition rate without altered body weight or calcium homeostatic hormone levels. A 20% increase in trabecular bone volume in transgenic vertebrae was also observed, unexpectedly associated with a 30% reduction in resorption surface rather than greater bone formation. These findings indicate anabolic vitamin D activity in bone and identify a previously unknown pathway from mature osteoblastic cells to inhibit osteoclastic bone resorption, counterbalancing the known stimulatory action through immature osteoblastic cells. A therapeutic approach that both stimulates cortical anabolic and inhibits trabecular resorptive pathways would be ideal for treatment of osteoporosis and other osteopenic disorders.

Type Journal
ISBN 0892-6638 (Print)
Authors Gardiner, E. M.;Baldock, P. A.;Thomas, G. P.;Sims, N. A.;Henderson, N. K.;Hollis, B.;White, C. P.;Sunn, K. L.;Morrison, N. A.;Walsh, W. R.;Eisman, J. A. :
Responsible Garvan Author A/Prof Paul Baldock
Publisher Name FASEB JOURNAL
Published Date 2000-01-01
Published Volume 14
Published Issue 13
Published Pages 1908-16
Status Published in-print
URL link to publisher's version