title: Advances in prevention and treatment of bone metastases in prostate cancer. Role of RANK/RANKL inhibition.
abstract: BACKGROUND
  Bone metastases are a common complication of prostate cancer, so treatment and prevention are essential to slow the progression of the disease and the occurrence of skeletal related events (SREs), which have devastating consequences for the quality of life of patients.
  
  
  METHODS
  Bone metastases are characterized by increased bone turnover and altered balance between osteogenesis and osteolysis, with activation of the RANK and its ligand (RANKL). In patients with metastatic prostate cancer, bisphosphonates have been the bone-targeted agents most commonly used to date. Zoledronic acid has demonstrated efficacy in the reduction and delay of SREs in patients with bone metastases. Denosumab, a RANKL inhibitor, has been demonstrated to be superior to zoledronic acid in the prevention of SREs in castration-resistant prostate cancer (CRPC). Both agents are being considered, along with other new bone-targeted agents, for the prevention of bone metastases in patients with nonmetastatic CRPC, where denosumab has already demonstrated superiority over placebo.
  
  
  CONCLUSIONS
  Denosumab and zoledronic acid prevent SREs in patients with prostate cancer and bone metastases. Denosumab also has a potential role in delaying bone metastases in nonmetastatic patients. Advances in the treatment of CRPC include an increasing focus on prevention of the progression of bone disease.
authors.affiliation: Servicio de Urología, Complejo Hospitalario Universitario, A Coruña, España. Electronic address: fgveiga@telefonica.net.
authors.forename: F
authors.initials: F
authors.lastname: Gomez-Veiga
authors.forename: J
authors.initials: J
authors.lastname: Ponce-Reixa
authors.forename: S
authors.initials: S
authors.lastname: Martinez-Breijo
authors.forename: J
authors.initials: J
authors.lastname: Planas
authors.forename: J
authors.initials: J
authors.lastname: Morote
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000517:prevention & control / Q000556:secondary*; D061067:Antibodies, Monoclonal, Humanized / Q000494:pharmacology / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D050071:Bone Density Conservation Agents / Q000494:pharmacology / Q000627:therapeutic use; D001859:Bone Neoplasms / Q000150:complications / Q000188:drug therapy / Q000517:prevention & control / Q000556:secondary*; D017326:Clinical Trials, Phase III as Topic; D000069448:Denosumab; D004164:Diphosphonates / Q000494:pharmacology / Q000627:therapeutic use; D004311:Double-Blind Method; D005544:Forecasting; D005598:Fractures, Spontaneous / Q000209:etiology / Q000517:prevention & control; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D008954:Models, Biological; D058990:Molecular Targeted Therapy; D015337:Multicenter Studies as Topic; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors* / Q000502:physiology; D017410:Practice Guidelines as Topic; D011471:Prostatic Neoplasms / Q000473:pathology*; D011788:Quality of Life; D053245:RANK Ligand / Q000037:antagonists & inhibitors* / Q000502:physiology; D016032:Randomized Controlled Trials as Topic; D053246:Receptor Activator of Nuclear Factor-kappa B / Q000502:physiology*; D000077211:Zoledronic Acid
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D007093:Imidazoles; D009363:Neoplasm Proteins; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; C505686:TNFRSF11A protein, human; C505688:TNFSF11 protein, human; D000069448:Denosumab; D000077211:Zoledronic Acid