TREATMENT

LOVASTATIN: A PREVENTATIVE FOR DEXAMETHASONE-INDUCED OSTEONECROSIS AND OSTEOPOROSIS

Xudong Li, Quanjun Cui, Heather Wilson, Gwo-Jaw, Wang, Gary Balian
Orthopaedic Research Laboratory, Department of Orthopaedic Surgery, School of Medicine Box 800374, University of Virginia, Charlottesville, VA, 22908

The mechanism whereby Lovastatin can counteract steroid-induced osteonecrosis and osteoporosis is poorly understood. We assessed the effect of Lovastatin on a pluripotential cell line, Dl, which is capable of differentiation to either osteoblast or adipocyte lineage. The expression of CBFal and PPARy, which are bone cell and fat cell transcription factors respectively, were determined semiquantitively by RT-PCR. Reporter gene activity was measured by cotransfecting the cells with the osteocalcin-promoter and reporter genes. Lovastatin enhanced osteoblast differentiation as assessed by a 2x increase in expression of CBFal and by a 5x increase in osteocalcin promoter activity. Expression of PPARy was decreased by 50%. Thus by enhancing osteoblast gene expression and by inhibiting adipogenesis, Lovastatin acts to shunt uncommitted osteoprogenitor cells in marrow from the adipocytic to the osteoblastic differentiation pathway. Future studies could be directed towards evaluating Lovastatin and other lipid-lowering drugs for the potential therapy of osteonecrosis and osteoporosis.