Statins: new drugs for treating osteoporosis?

Statins are widely used lipid-lowering drugs that reduce cholesterol synthesis by inhibiting 3-hydroxy-3-glutaryl-coenzyme A (HMG-CoA) reductase activity. They also strongly stimulate bone formation in rodents. If the drugs' potent bone-building activity results directly from inhibition of HMG-CoA reductase, there should be less bone fracturing in humans who have taken statins to lower their serum cholesterol and prevent heart attacks, but the data gleaned from several databases are contradictory. According to some reports the lipid-lowering doses of oral statins increased bone mineral density and more than halved the risk of fracturing various bones, while according to others, including the very large Women's Health Initiative Observational Study (WHI-OS), the drugs did not significantly affect the fracturing risk. Such contradictory data could be due in part to one of the commonly used statins, pravastatin which only targets hepatocytes, or due to bone growth being stimulated by something other than inhibition of HMG-CoA reductase. Therefore, different doses of statins may be needed to build bone or optimally lower serum cholesterol. To be able to answer the question posed by the title of this editorial, it will be necessary to carry out a controlled trial using designer statins that are less liver-oriented and thus better for assessing the optimal doses needed, specifically for osteogenicity rather than for their cholesterol-lowering ability.