Statins and Osteoporosis: A Clinical Review

Michael J. Gonyeau, Pharm.D.


Pharmacotherapy. 2005;25(2):228-243. 

In This Article


The use of statins in the prevention of fractures or the treatment of osteoporosis continues to require further study. Although in vitro, in vivo, and animal studies have shown positive effects on bone mineralization and reductions in bone resorption, clinical data on surrogate markers and fracture rates are conflicting. In addition, the inherent problems with observational studies must be addressed. Despite attempts to control for potential confounders, one cannot determine causality of any relationship with this type of trial. This is of particular importance when comparing the observational trial data with the limited prospective trial data, which reveal various effects on clinical fracture outcomes.

The inherent problem with observational studies is most evident in the two trials conducted with use of the GPRD.[57,58] Although in each trial the authors performed their analyses with the same database, they came to categorically opposite conclusions. In more closely evaluating each trial ( Table 3 ), some potentially significant differences can be seen in trial design, patient identification methods, statin use definitions, inclusion and exclusion criteria, confounders controlled for, and diagnostic methods used. Many of these differences may have accounted for the disparity in the results of these studies, highlighting the potential variability of this study type and the importance of patient identification techniques.

Many of the studies in this review conclude that additional large, prospective trials should be conducted to evaluate the role of statins in the treatment of osteoporosis. This is a common conclusion when conducting observational studies that cannot prove causality, but what would the ideal trial on statins in osteoporosis look like? Table 4 outlines many attributes listed in the clinical fracture studies that were reviewed. Each clinical trial is also listed to demonstrate how individual studies compare with these self-defined attributes.

One must remember that the available statins are labeled for the treatment of cardiovascular disease, specifically the lowering of serum cholesterol levels. These agents target the liver as their primary site of action. It is unknown how human bone would be affected with higher concentrations of statins, or even if formulations could be constructed to achieve the desired concentrations. Is the oral route best? What about a transdermal patch or subcutaneous injection that would attempt to bypass the significant metabolism through the liver from the oral route? Additional questions that need to be asked and answered include the following: What is the final outcome of this research? Should statins replace bisphosphonates as the treatment of choice for osteoporosis? Would they be considered as an adjunct to such therapies? Should millions of dollars be spent researching and potentially developing "bone-specific" statins? Time will tell.


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