title: New anti-resorptives and antibody mediated anti-resorptive therapy.
abstract: The ageing population and an increase in both the incidence and prevalence of cancer pose a healthcare challenge, some of which is borne by the orthopaedic community in the form of osteoporotic fractures and metastatic bone disease. In recent years there has been an increasing understanding of the pathways involved in bone metabolism relevant to osteoporosis and metastases in bone. Newer therapies may aid the management of these problems. One group of drugs, the antibody mediated anti-resorptive therapies (AMARTs) use antibodies to block bone resorption pathways. This review seeks to present a synopsis of the guidelines, pharmacology and potential pathophysiology of AMARTs and other new anti-resorptive drugs. We evaluate the literature relating to AMARTs and new anti-resorptives with special attention on those approved for use in clinical practice. Denosumab, a monoclonal antibody against Receptor Activator for Nuclear Factor Kappa-B Ligand. It is the first AMART approved by the National Institute for Health and Clinical Excellence and the US Food and Drug Administration. Other novel anti-resorptives awaiting approval for clinical use include Odanacatib. Denosumab is indicated for the treatment of osteoporosis and prevention of the complications of bone metastases. Recent evidence suggests, however, that denosumab may have an adverse event profile similar to bisphosphonates, including atypical femoral fractures. It is, therefore, essential that orthopaedic surgeons are conversant with these medications and their safe usage.
  
  
  CONCLUSIONS
  Denosumab has important orthopaedic indications and has been shown to significantly reduce patient morbidity in osteoporosis and metastatic bone disease.
authors: Freeman Hospital, Newcastle, UK.
authors: A J
authors: AJ
authors: Farrier
authors: Stepping Hill Hospital, Stockport, UK.
authors: L C
authors: LC
authors: Sanchez Franco
authors: Hull Royal Infirmary, Hull, UK.
authors: A
authors: A
authors: Shoaib
authors: Chelsea and Westminster Hospital, London, UK.
authors: V
authors: V
authors: Gulati
authors: University Hospitals of Leicester, Leicester, UK.
authors: N
authors: N
authors: Johnson
authors: Harcourt House, Sheffield, UK.
authors: C E
authors: CE
authors: Uzoigwe
authors: Royal Orthopaedic Hospital, Birmingham, UK.
authors: M Z
authors: MZ
authors: Choudhury
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D061067:Antibodies, Monoclonal, Humanized / Q000494:pharmacology / Q000627:therapeutic use*; D059266:Bisphosphonate-Associated Osteonecrosis of the Jaw / Q000209:etiology; D050071:Bone Density Conservation Agents / Q000494:pharmacology / Q000627:therapeutic use*; D019485:Bone Morphogenetic Proteins / Q000037:antagonists & inhibitors; D001859:Bone Neoplasms / Q000188:drug therapy / Q000556:secondary; D001862:Bone Resorption / Q000188:drug therapy*; D003362:Cost-Benefit Analysis; D000069448:Denosumab / Q000494:pharmacology / Q000627:therapeutic use*; D004164:Diphosphonates / Q000627:therapeutic use; D017277:Drug Approval; D005264:Femoral Fractures / Q000139:chemically induced; D005819:Genetic Markers; D006801:Humans; D006996:Hypocalcemia / Q000139:chemically induced; D010024:Osteoporosis / Q000188:drug therapy; D058866:Osteoporotic Fractures / Q000188:drug therapy; D017410:Practice Guidelines as Topic; D019057:Quality-Adjusted Life Years; D053245:RANK Ligand / Q000037:antagonists & inhibitors
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D061067:Antibodies, Monoclonal, Humanized; D050071:Bone Density Conservation Agents; D019485:Bone Morphogenetic Proteins; D004164:Diphosphonates; D005819:Genetic Markers; D053245:RANK Ligand; C422903:SOST protein, human; C505688:TNFSF11 protein, human; D000069448:Denosumab
keywords: denosumab; metastatic bone disease; osteoporosis