Statins and Osteoporosis: A Clinical Review

Michael J. Gonyeau, Pharm.D.

Disclosures

Pharmacotherapy. 2005;25(2):228-243. 

In This Article

Abstract and Introduction

Osteoporosis is a leading public health threat affecting approximately 44 million people in the United States. Most of the therapies for this disease work to prevent further bone loss, improve bone mineral density, and reduce the risk of fractures. These agents, however, have not been proved to increase bone formation significantly. Therefore, the ideal agent would not only improve bone strength by decreasing bone breakdown, but also promote bone formation in the ultimate quest to prevent fractures. The 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) have become an area of research in the battle against osteoporosis. Two mechanisms for beneficial effects of statins on bones have been proposed, and 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. The inherent problems with observational studies also must be addressed. Until that time, the use of statins in the prevention of fractures or the treatment of osteoporosis requires further study.

Osteoporosis is defined by the National Osteoporosis Foundation as a disease characterized by low bone mass and structural deterioration of bone tissue, leading to bone fragility and an increased risk of fracture.[1] Osteoporosis is a leading public health threat that affects approximately 44 million people in the United States. An estimated 10 million Americans have osteoporosis, of which 80% are women, and an additional 34 million have low bone mass, placing them at an increased risk for osteo-porosis. Every year, osteoporosis is responsible for approximately 1.5 million fractures, with the most common being hip, spine, and wrist; these fractures led to a reported $17 billion in direct costs in 2001.[2] Consequently, osteoporosis is an enormous human and economic burden that is expected to become more significant over time as a result of the increasing elderly population.

Although the exact pathophysiology of osteoporosis is unknown, the disease occurs when the activity of osteoclasts (cells responsible for the removal of bone) exceeds that of osteoblasts (cells responsible for the formation of new bone). Treatment strategies have been designed to restore the balance between bone resorption and formation largely by inhibiting osteoclast activity, or by stimulating bone formation. Several over-the-counter and prescription drugs are used in the treatment and/or prevention of osteoporosis, including calcium and vitamin D supplementation, bisphosphonates,[3,4,5,6,7,8,9,10] hormone replacement therapy (HRT),[11,12,13,14,15] raloxifene,[16,17,18] calcitonin,[19,20] and teriparatide.[21,22]

Many of these drugs work to prevent further bone loss, improve bone mineral density (BMD), and reduce the risk of fractures. However, most of these agents have not been proved to increase bone formation significantly. Therefore, the ideal agent would not only improve bone strength by decreasing bone breakdown, but also promote bone formation in the ultimate quest to prevent fractures.

Teriparatide is a synthetic parathyroid hormone analog proved to increase bone formation and reduce the risk for osteoporosis-related fractures in clinical trials.[21,22] It is approved for postmenopausal women and hypogonadal men with osteoporosis. Potential complications associated with teriparatide include its lack of an oral formulation and its increased potential for osteosarcoma.

Research is ongoing in the search for new compounds with bone-building effects, with interesting results. One group of authors observed that intermittent nitrate use was associated with increased BMD at the hip and heel in more than 6000 elderly women.[23] The proposed mechanism for clinical improvement due to nitrates is increased bone growth without increased bone breakdown. Preliminary results suggest decreased bone breakdown similar to that with bisphosphonates, and a potential increase in bone formation by as much as 20%.[24]

One of the most intense areas of research for new compounds to battle the scourge of osteo-porosis has centered on 3-hydroxy-3-methyl-glutaryl coenzyme A (HMG-CoA) reductase inhibitors, or statins.[25,26,27,28,29,30,31,32]

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