Statins and osteoporosis: A latent promise Estatinas y osteoporosis: una promesa latente

The clinical use of statins as therapeutic tools for osteoporosis has not yet reached the status of solid scientific dogma, even though it has been almost 15 years since the emergence of the first experimental evidence on the effect of this class of drugs on bone metabolism, specifically stimulating the formation of “new bone”. Statins are a groupof competitive inhibitors consistingof the hydroxy-methyl-glutaryl-CoA (HMG-CoA) reductase and therefore have been widely used for the treatment of hypercholesterolemia. Thefirst experimental evidence in an animalmodel of the osteomodulador effect of statins was reported by Mundy et al.,1 who demonstrated that treatment with lovastatin, simvastatin, fluvastatin and mevastatin resulted in a significant increase (up to 2–3 times compared with controls) in the rates and bone formation markers, and that the effect of statins were comparable to that induced by treatmentwith bonemorphogenetic protein-2 (BMP-2) and fibroblast growth factor, which are known stimulants of bone metabolism.2 Other studies conducted in animalmodels, replicated the effects of statins as stimulating bone formation. However, the application of this knowledge to the treatment of metabolic bone diseases in humans has not been able to find solid support, as studies in humans have shown conflicting results. The potential positive effect of statins on bone formation can be explained from three mechanisms: (a) the promotion of osteogenesis (b) suppression of apoptosis of osteoblasts and (c) inhibition of osteoclastogenesis.3 The promotion of osteogenesis appears to be linked to mechanisms of prenylation as a posttranslational modification and necessary for certain key proteins in some signaling cascades. The HMG-CoAreductase enzymecatalyzes the synthesis ofmevalonate, which is a limiting step for the formation reactions of farnesyl pyrophosphate and geranyl isoprenoids, which are the initial actions for the synthesis of cholesterol. The major effect of the statins is a decrease of the catalytic activity of HMG-CoA reductase, for the transformation of HMG-CoA tomevalonate, and finally