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HMG-CoA Reductase Inhibitors in Osteoporosis

Do They Reduce the Risk of Fracture?

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Abstract

Osteoporosis affects a large number of people in industrialised countries. It has clinical and public-health impacts, most importantly due to subsequent fractures. Osteoporotic fractures are one of the most common causes of disability and are associated with enormous healthcare expenditure. The majority of existing treatment options for osteoporosis only inhibit bone resorption and prevent excessive bone loss but are not capable of stimulating bone formation. However, several recent in vitro and in vivo studies in animals demonstrated that HMG-CoA reductase inhibitors stimulate the production of bone morphogenetic protein (BMP-2), which is a potent regulating protein in osteoblast differentiation and activity. This suggests that HMG-CoA reductase inhibitors may have an anabolic effect on bones, making them a potentially interesting treatment option for osteoporosis. Additionally, several studies in humans showed that some HMG-CoA reductase inhibitors may have a beneficial effect on bone turnover and may lead to an increase in bone mineral density.

Consequently, several observational studies tried to evaluate whether use of HMG-CoA reductase inhibitors is associated with a decreased risk of fractures. Even though not all results of these epidemiological studies, using different designs in different study populations, were entirely consistent, they provided substantial evidence that HMG-CoA reductase inhibitor use may decrease the bone fracture risk by approximately 50%. On the other hand, reanalyses of two randomised controlled trials of HMG-CoA reductase inhibitor therapy, designed to assess cardiovascular outcomes, could not show that patients treated with HMG-CoA reductase inhibitors had a lower fracture risk in comparison with placebo-treated patients.

Therefore, to conclusively assess the potential of HMG-CoA reductase inhibitors in the prevention and treatment of osteoporosis, randomised controlled trials need to be performed to address this conflicting issue. Until the results of such trials are available, practitioners should prescribe the drugs that have been proven to reduce the risk of osteoporotic fractures.

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Acknowledgements

Christoph R. Meier is recipient of a grant from the Swiss National Science Foundation (grant number 32-056 751). The Boston Collaborative Drug Surveillance Program is supported in part by grants from AstraZeneca, Bayer AG, Berlex Laboratories, Boehringer Ingelheim Pharmaceuticals, Inc., Boots Healthcare International, Bristol-Myers Squibb Pharmaceutical Research Institute, Glaxo Wellcome Inc., Hoffmann-La Roche Ltd, Janssen Pharmaceutica, L.P., RW Johnson Pharmaceutical Research Institute, McNeil Consumer Products Company, Novartis Farmacéutica, S.A., and Searle. The authors have no conflicts of interest that are directly relevant to the content of this manuscript.

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Authors and Affiliations

  1. Basel Pharmacoepidemiology Unit, Division of Clinical Pharmacology & Toxicology, University Hospital, Basel, CH-4031, Switzerland

    Raymond G. Schlienger & Christoph R. Meier

  2. Department of Pharmacy, Institute of Clinical Pharmacy, University of Basel, Basel, Switzerland

    Raymond G. Schlienger

  3. Boston Collaborative Drug Surveillance Program, Boston University Medical Center, Lexington, Massachusetts, USA

    Christoph R. Meier

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Correspondence to Raymond G. Schlienger.

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Schlienger, R.G., Meier, C.R. HMG-CoA Reductase Inhibitors in Osteoporosis. Drugs Aging 20, 321–336 (2003). https://doi.org/10.2165/00002512-200320050-00002

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