Genetics of the bone response to bisphosphonate treatments

Bone mineral density (BMD) is the best established marker for bone health. Over the last years a large number of studies have pointed to the variability in many target genes and their relation with bone mass and with other determinants of fracture risk such as ultrasound bone properties, skeletal geometry and bone turnover markers. The importance of genetic factors in the bone quality is substantial, but no consensus exists yet on the genes that are involved. Furthermore, there are many differences of clinical outcomes during bone-active treatments in the population-based studies. Heterogeneity in drug response may reflect varying responsiveness to boneactive treatments due to allele variation in the polymorphic target genes. In this regard, polymorphisms of vitamin D receptor and estrogen receptor loci appear genetic determinants of their corresponding hormonal treatment response such as vitamin D and estrogens. The present review focuses on the genetic determinants involved in the clinical response to bisphosphonate treatments for bone disorders. Knowledge of the molecular and functional consequences of the target genes is crucial to fully appreciate their significance and understand their potential clinical implications.