Mechanisms of Bone Anabolism Regulated by Statins.

Bioscience Reports (Impact Factor: 1.88). 07/2012; DOI: 10.1042/BSR20110118
Source: PubMed

ABSTRACT Osteoporosis is a common disease in the elderly population. The progress of this disease results in the reduction of bone mass and can increase the incidence of fractures. Drugs presently used clinically can block the aggravation of this disease. However, these drugs cannot increase the bone mass and may result in certain side effects. Statins, also known as 3-hydroxy-3-methyl-glutarylcoenzyme A (HMG-CoA) reductase inhibitors, are widely prescribed for cardiovascular disease for decades. Nonetheless, accumulating studies demonstrate that statins exert bone anabolic effect and may be helpful for the treatment of osteoporosis. Abundant of experiments have analyzed the mechanisms of bone anabolism regulated by statins. In the present paper, we review the mechanisms of promoting osteogenesis, suppressing osteoblast apoptosis and inhibiting osteoclastogenesis.

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    ABSTRACT: The discovery that statins had bone anabolic properties initiated many investigations into their use for treatment of bone catabolic diseases, such as osteoporosis. This paper reviews the molecular basis of statin's role in bone metabolism, and animal and human studies on the impact of systemic statins on osteoporosis-induced bone fracture incidence and healing, and on bone density. Limitations of systemic statins are described along with alternative dosing strategies, including local applications and bone-targeting systemic preparations. The principal findings of this review are: 1) traditional oral dosing with statins results in minimal efficacy in the treatment of osteoporosis; 2) local applications of statins show promise in the treatment of accessible bony defects, such as periodontitis; and 3) systemically-administered statins which can target bone or inflammation near bone may be the safest and most effective strategy in the treatment of osseous deficiencies.
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    ABSTRACT: Context Tooth extraction and periodontal disease are both common clinical situations associated with alveolar bone loss. Purpose The objective was to analyze the reported results of in vivo studies investigating the effectiveness of statins to reduce alveolar bone resorption. Material and methods Systematic electronic search of the MEDLINE-Pubmed database. Results A total of 21 studies satisfied the inclusion criteria. This review showed that the use of statins reduced significantly alveolar bone resorption observed during periodontal disease and after tooth extraction. Oral administration was effective using high statin concentrations although local administration using a biodegradable carrier was effective with lower concentrations. It was recently reported that statins were effective to reduce alveolar bone loss as an adjunct to SRP in several clinical trials. Further studies are needed to confirm these promising results.
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    ABSTRACT: Although their primary therapeutic indications are different, aminobisphosphonates and statins target enzymes in the mevalonate pathway, which is critical for bone homeostasis. Previous studies have shown that some polymorphisms of the gene encoding farnesyl diphosphate synthase (FDPS), the main target of aminobisphosphonates, modulate the response to these drugs. In this study, we explored whether those single nucleotide polymorphisms (SNPs) also influence the changes in bone mineral density (BMD) following therapy with statins. Sixty-six patients with coronary heart disease were studied at baseline and after 1-year therapy with atorvastatin. BMD was measured by DXA. Three SNPs of the FDPS gene (rs2297480, rs11264359 and rs17367421) were analyzed by using Taqman assays. The results showed that there was no association between the SNPs and basal BMD. However, rs2297480 and rs11264359 alleles, which are in linkage disequilibrium, were associated with changes in hip BMD following atorvastatin therapy. Thus, patients with AA genotype at the rs2297480 locus had a 0.8 ± 0.8 % increase in BMD at the femoral neck, whereas in patients with AC/CC genotypes, BMD showed a 2.3 ± 0.8 % decrease (p = 0.02). Similar results were obtained regarding changes of BMD at the femoral trochanter and when alleles at the rs11264359 locus were analyzed. However, there was no association between BMD and rs17367421 alleles. In conclusion, these results suggest that polymorphisms of the FDPS gene may influence the bone response to various drugs targeting the mevalonate pathway, including not only aminobisphosphonates but also statins.
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