title: Genetic and acquired factors influencing the effectiveness and toxicity of drug therapy in osteoporosis.
abstract: BACKGROUND
  Osteoporosis is a highly prevalent skeletal disorder characterized by compromised bone strength, usually related to decreased bone mass and microstructural alterations of bone tissue, predisposing a person to an increased risk of fracture. As other prevalent disorders, osteoporosis is the result of a complex interplay of genetic and acquired factors.
  
  
  METHODS
  We provide an update of recent studies aimed at identifying the clinical and genetic factors that influence the response to drugs used to treat osteoporosis, as well as those determining the risk of two intriguing adverse effects of antiresorptives: osteonecrosis of the jaw (ONJ) and atypical femoral fractures (AFF).
  
  
  CONCLUSIONS
  Several clinical factors have been suggested to increase the risk of a poor drug response, such as advanced age and frailty. Candidate gene studies suggest that some common polymorphisms of the Wnt pathway and farnesyl diphosphate synthase (FDPS), the target enzyme for bisphosphonates, also influence the response to antiresorptives. However, they await for replication in large independent cohorts of patients. Similarly, some genetic and acquired factors may influence the risk of ONJ and AFF. Preliminary data suggest that the risk of suffering these adverse effects may have a polygenic basis.
authors.affiliation: a Department of Medicine and Service of Rheumatology (LRZ) , Hospital U.M. Valdecilla, University of Cantabria, IDIVAL, RETICEF , Santander , Spain.
authors.forename: Laura
authors.initials: L
authors.lastname: López-Delgado
authors.affiliation: a Department of Medicine and Service of Rheumatology (LRZ) , Hospital U.M. Valdecilla, University of Cantabria, IDIVAL, RETICEF , Santander , Spain.
authors.forename: Leyre
authors.initials: L
authors.lastname: Riancho-Zarrabeitia
authors.affiliation: a Department of Medicine and Service of Rheumatology (LRZ) , Hospital U.M. Valdecilla, University of Cantabria, IDIVAL, RETICEF , Santander , Spain.
authors.forename: José A
authors.initials: JA
authors.lastname: Riancho
mesh_terms: D050071:Bone Density Conservation Agents / Q000008:administration & dosage* / Q000633:toxicity*; D016723:Bone Remodeling / Q000187:drug effects; D004164:Diphosphonates / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005264:Femoral Fractures / Q000188:drug therapy / Q000235:genetics; D051228:Geranyltranstransferase / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007571:Jaw Diseases / Q000188:drug therapy / Q000235:genetics; D010020:Osteonecrosis / Q000188:drug therapy / Q000235:genetics; D010024:Osteoporosis / Q000188:drug therapy* / Q000235:genetics*; D060449:Wnt Signaling Pathway
chemical_list: D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D051228:Geranyltranstransferase
keywords: Atypical femoral fractures; bisphosphonates; denosumab; fractures; osteonecrosis of the jaw; osteoporosis; pharmacogenetics