Pharmacogenomics of Osteoporosis

Abstract

Pharmacogenomics and pharmacogenetics are emerging interdisciplinary areas recently defined, respectively as ''the investigation of variations of DNA and RNA characteristics as related to drug response'', and the study of ''the influence of variations in DNA sequence on drug efficacy and toxicity''. A major challenge of future genetic studies in complex disorders such as osteoporosis is the development of specific genetic tests to identify responders from non-responders as well as to identify patients at higher risk to develop adverse reactions. Even though the knowledge of the genetic determinants of bone fragility and fracture risk has consistently increased over the past decade and despite the parallel development of multiple drugs with antiresorptive or anabolic activity in bone, there is still relatively little known about pharmacogenomics and pharmacogenetics of osteoporosis. This review provides an overview of available information and identifies potential targets for future studies in this field.

The effect of vitamin D receptor BsmI genotype on the response to osteoporosis treatment in postmenopausal women: A pilot study

“…First evidence for an interaction between calcium intake and BsmI VDR polymorphism came from a study by Ferrari et al 19 in a sample of elderly patients receiving calcium and calcitriol supplements, among whom BMD loss was higher in the lumbar spine of the homozygotes for the B allele. Similar results, indicative of the genetreatment interaction, were found in other studies (for a review see Gennari 21 ) were the BB genotype associated with higher response to calcium administration, reduced efficiency of calcium absorption and low response of BMD. Furthermore, a large-scale study 15 reported evidence of weak interactions between calcium intake, VDR variants and BMD as well as with rates of bone loss in a way that favored the bb homozygotes in the lowest calcium intake quartile.…”

“…Furthermore, animal studies 32 suggested that teriparatide shifts stem cells towards the osteoblasts linage. However, teriparatide's effect has not been evaluated in pharmacogenomic studies yet 21 . The results of the present pilot study suggest that in contrast to alendronate, no interaction seems to exist between VDR BsmI polymorphism and teriparatide treatment.…”

“…In this manner, the VDR gene regulates calcium absorption, bone mineralization and remodeling. Environmental factors, 17,18 calcium and vitamin D intake [19][20][21] or antiresorptive treatment [21][22][23][24] have been suggested to alter the VDR BsmI genotype impact on BMD and fracture risk, suggesting an interactive model of environmental influence.…”

Common allelic variants of the farnesyl diphosphate synthase gene influence the response of osteoporotic women to bisphosphonates

“…They included the vitamin D receptor, estrogen receptors, collagen and lipoprotein receptor-related protein (a Wnt coreceptor), but the results have not been adequately replicated. 16,23,24 In this study, we analyzed the relationship of several polymorphisms of the gene encoding the FDPS enzyme, a major target of aminobisphosphonates, with BMD and drug response in postmenopausal women. We only found a quantitatively small and not significant trend for association of one of the SNPs studied with baseline hip BMD.…”

“…14,15 Similarly, little is known about the pharmacogenomics of osteoporosis, and specifically about the possible influence of genetic factors on the therapeutic effects of antiosteoporotic drugs. 16 The aim of this study was to analyze the influence of FDPS polymorphisms on BMD and the response to antiresorbing drugs.…”