title: Palliative Oncology: Denosumab.
abstract: Bone metastases cause devastating clinical complications leading patients to have pain, poor quality of life, loss of mobility, and autonomy. Complications from osseous metastases cause a big economic burden reflected by repeated admissions for uncontrolled symptoms. Management of symptoms associated with bone metastasis includes systemic analgesics, glucocorticoids, radiation (external beam radiation and radiopharmaceuticals), ablative techniques (radiofrequency ablation and cryoablation), chemotherapeutic agents, hormonal therapies, interventional techniques (eg, kyphoplasty), and surgical approaches. Bisphosphonates have become a standard therapy for bony metastasis. They bind to bone eventually inhibiting osteoclast action. Bisphosphonates decrease fractures when given routinely. Adverse effects of bisphosphonates include osteonecrosis of the jaw and renal insufficiency. Late last year, the Food and Drug Administration approved denosumab to prevent skeletal-related events (SREs) associated with metastatic solid tumors. This drug is a monoclonal antibody that inhibits the receptor activator of nuclear factor κB (RANK)-RANK ligand interaction. Clinical trials have shown superiority over bisphosphonates for the prevention of SREs. This article reviews the mechanism of action, pharmacology, adverse effects, and clinical trial evidence for this new drug.
authors.affiliation: Division of Hematology/Oncology, Mayo Clinic College of Medicine, Mayo Clinic Hospital, Scottsdale, AZ, USA prommer.eric@mayo.edu.
authors.forename: Eric
authors.initials: E
authors.lastname: Prommer
mesh_terms: D014408:Biomarkers, Tumor; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000556:secondary*; D002986:Clinical Trials as Topic; D000069448:Denosumab / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D004164:Diphosphonates / Q000627:therapeutic use; D017277:Drug Approval; D006801:Humans; D011788:Quality of Life; D053245:RANK Ligand / Q000037:antagonists & inhibitors*; D014481:United States; D014486:United States Food and Drug Administration
chemical_list: D014408:Biomarkers, Tumor; D004164:Diphosphonates; D053245:RANK Ligand; C505688:TNFSF11 protein, human; D000069448:Denosumab
keywords: RANK; bisphosphonates; denosumab; osteoprotegerin; pain; prostate cancer