Pharmacogenetics of osteoporosis-related bone fractures: moving towards the harmonization and validation of polymorphism diagnostic tools

Abstract

Osteoporosis is one of the most common skeletal chronic conditions in developed countries, hip fracture being one of its major healthcare outcomes. There is considerable variation in the implementation of current pharmacological treatment and prevention, despite consistent recommendations and guidelines. Many studies have reported conflicting findings of genetic associations with bone density and turnover that might predict fracture risk. Moreover, it is not clear whether genetic differences exist in relation to the morbidity and efficiency of the pharmacotherapy treatments. Clinical response, including beneficial and adverse events associated with osteoporosis treatments, is highly variable among individuals. In this context, the present article intends to summarize putative candidate genes and genome-wide association studies that have been related with BMD and fracture risk, and to draw the attention to the need for pharmacogenetic methodology that could be applicable in clinical translational research after an adequate validation process. This article mainly compiles analysis of important polymorphisms in osteoporosis documented previously, and it describes the simple molecular biology tools for routine genotype acquisition. Validation of methods for the easy, fast and accessible identification of SNPs is necessary for evolving pharmacogenetic diagnostic tools in order to contribute to the discovery of clinically relevant genetic variation with an impact on osteoporosis and its personalized treatment.