Potential new drug treatment for osteoporosis
Osteoporosis is a global health problem that will take on increasing significance as people live longer and the worlds population continues to increase. Current treatments have been restricted by a lack of drugs capable of restoring bone mass to normal levels. This situation may be about to change with the discovery of beneficial bone-restoration effects of statins.
Greg Mundy and colleagues in the USA have reported that statins, compounds currently in use to lower blood cholesterol levels, induced significant bone growth in mouse bone cell cultures and also in rats and mice in vivo.a If similar effects were observed in humans, statins would offer an effective treatment for those suffering from osteoporosis.
Mundy and co-workers screened 30 000 compounds in an attempt to find potential drug candidates with favourable effects on bone mass. Using a luciferase reporter-gene assay, the researchers looked for compounds that would activate the promoter of the bone morphogenetic protein-2 (BMP-2) gene. Lovastatin was observed in the initial screening to increase luciferase activity in the in vitro assay. When injected subcutaneously into tissue overlying the murine calvaria in live rats, a 50% increase in new bone formation was observed after five days of treatment.
To optimize potential treatments, the challenge will be to identify or synthesize related compounds that distribute themselves preferentially to bone or bone marrow. Pierre Delmas, President of the International Osteoporosis Foundation, told the Bulletin: "Statins are potentially good drugs for the treatment of osteoporosis. They appear to stimulate bone formation without increasing bone resorption. However, the currently marketed statins are unlikely to be used for the treatment of osteoporosis as they are not specific enough to target bone. Its the new statins, currently in development, that are more bone-specific and which offer the greatest promise." The work by Mundy and colleagues offers a step in this direction and may permit identification of compounds that may one day lead to effective oral treatments for osteoporosis.
a Mundy et al. Stimulation of bone formation in vitro and in rodents by statins. Science, 1999, 286: 19461949.