Is there a connection between the cholesterol-lowering drugs known as statins and improved bone health? Recently, news reports seemed to indicate one. But how strong is the connection? And just what could it mean for the millions of people with osteoporosis?

The possible connection between statins and bone health was first announced in 1999. A team of scientists tested more than 30,000 drugs looking for compounds that would stimulate the production of a protein critical to bone formation. Only statins increased the levels of the bone formation protein.

In follow-up studies on mice and rats, the researchers found statins directly targeted to bone or bone marrow increased bone formation by almost 50 percent in just five days. Orally-administered statins took longer and showed a smaller increase in bone formation. The mechanism of possible action was not clearly defined.

Statins have been available to the public for more than 10 years as cholesterol-lowering drugs. They have been proven beneficial for people at risk of coronary heart disease and stroke. Thus, if a connection to bone-formation exists, it could be reviewed through retrospective studies of people already taking the drug.

That's precisely the response the initial announcement generated. Over the past year, several retrospective studies were conducted in the United States, England, Switzerland and Japan. Although some of the studies seemed to support the connection between statins and bone health, others questioned any benefit.

• A study at Boston's Brigham and Women's Hospital found that statins seem to be mildly protective against non-pathological fracture among older women. The study compared statin use between a group of controls and a group of women over age 60 who had experienced a fracture of the hip, upper arm, lower leg, wrist or spine during a one-year period.
• Another group of investigators from Brigham and Women's Hospital reviewed records of elderly patients enrolled in New Jersey public assistance health-care programs. They also found that statin use seemed to be associated with a significantly reduced risk of hip fracture.
• In London, doctors compared bone mineral density (BMD), indicator of bone health, between a group of women taking statins and a group of controls. After adjusting for age, weight, and height, they found that statin users had significantly higher measures of BMD.
• The Swiss study compared the use of statins with other cholesterol-reducing drugs. Researchers found that patients who took statins had a significantly reduced fracture risk not seen in patients who took other cholesterol-reducing drugs.
• However, a Japanese study of patients with type 2 diabetes seemed to indicate a negative correlation between statin use and BMD. That is, patients taking statins had a lower BMD than those not on the drug.
• Researchers from the Women's Health Initiative Observational Study compared the rates of hip, lower arm or wrist and other clinical fractures among current and non-users of statins. They found that fracture rates in both groups were similar, regardless of how long or what kind of statin was used. An examination of bone mineral density among statin users and non-users found that the differences were not statistically significant.
• The most recent study involved a secondary analysis of data from the Long-term Intervention with Pravastatin in Ischaemic Disease (LIPID) trial. The analysis of women, participants aged 65 years and older, and the entire study showed no evidence of a reduced frequency of fracture in patients treated with pravastatin.

The controversy over the connection between statins and bone health reinforces the need for controlled trials before any treatment is adopted or altered. Statin drugs are taken by about 8 million Americans to treat high cholesterol levels. But individuals with high cholesterol are often not at risk for osteoporosis. Additionally, there are several different types of statin drugs, each with different dosage levels. No randomized controlled blended study has yet been done to determine whether statin drugs are effective in individuals with osteoporosis.

Most doctors who work with osteoporosis are taking a cautionary approach to the news about statins. Current treatments such as bisphosphonates and hormone replacement therapy can cut the risk of fracture almost in half. Doctors warn that statins should not be used as a substitute for these treatments.