Genetic and acquired factors influencing the effectiveness and toxicity of drug therapy in osteoporosis

摘要

Introduction: Osteoporosis is a highly prevalent skeletal disorder characterized by compromised bone\udstrength, usually related to decreased bone mass and microstructural alterations of bone tissue,\udpredisposing a person to an increased risk of fracture. As other prevalent disorders, osteoporosis is\udthe result of a complex interplay of genetic and acquired factors.\udAreas covered: We provide an update of recent studies aimed at identifying the clinical and genetic\udfactors that influence the response to drugs used to treat osteoporosis, as well as those determining the\udrisk of two intriguing adverse effects of antiresorptives: osteonecrosis of the jaw (ONJ) and atypical\udfemoral fractures (AFF).\udExpert opinion: Several clinical factors have been suggested to increase the risk of a poor drug\udresponse, such as advanced age and frailty. Candidate gene studies suggest that some common\udpolymorphisms of the Wnt pathway and farnesyl diphosphate synthase (FDPS), the target enzyme for\udbisphosphonates, also influence the response to antiresorptives. However, they await for replication in\udlarge independent cohorts of patients. Similarly, some genetic and acquired factors may influence the\udrisk of ONJ and AFF. Preliminary data suggest that the risk of suffering these adverse effects may have a\udpolygenic basis.