- Paper Report
- Open Access
Bone anabolic effects of statins
- Mike Rogers1
© Current Science Ltd 2000
- Published: 10 January 2000
Excessive osteoclast activity and loss of bone are characteristic features of diseases such as post-menopausal osteoporosis and rheumatoid arthritis. Although bone resorption can be prevented by agents such as bisphosphonates, estrogen or selective estrogen receptor modulators, there are currently no drugs available with bone anabolic properties capable of replacing substantial amounts of bone. To identify agents that may stimulate the production of bone morphogenetic protein (BMP)-2 by osteoblasts (bone-forming cells). Since BMP-2 is a powerful stimulator of osteoblast differentiation, such agents could have anabolic effects on bone in vivo.
Using the reporter assay, BMP-2 expression was stimulated by 1-5 ?molar of the fungal metabolite lovastatin, and the related statins fluvastatin, mevastatin and simvastatin. These compounds also stimulated BMP-2 production by osteoblasts, and increased osteoblast proliferation and bone formation in organ cultures of bone in vitro and when injected over the calvaria of mice. Finally, oral administration of simvastatin increased the volume of trabecular bone and increased the rate of bone formation in normal and ovariectomised rats.
A reporter construct consisting of the BMP-2 promoter linked to the firefly luciferase gene was transfected into an osteoblast cell line, and used to screen a library of over 30,000 natural compounds to identify agents that could stimulate BMP-2 expression.