title: Adjuvant therapy with bone-targeted agents.
abstract: OBJECTIVE
  The use of bone-targeting agents in the adjuvant setting has focused on two main areas: prevention of chemotherapy-induced bone loss (CTIBL) and the potential antitumour effects in preventing development of metastasis. Here, we review recent advances within these two areas.
  
  
  RESULTS
  Trials of oral and intravenous bisphosphonates for prevention of CTIBL in breast cancer have informed both UK and European guidelines on management. A large randomized trial of denosumab, an antibody to RANK ligand, in prostate cancer has demonstrated prevention of bone loss and a reduction in fractures. The data supporting the use of bone-targeted agents in prevention of metastasis are less consistent, with variable findings from the randomized controlled trials in both breast and prostate cancer reported to date. However, the emerging evidence suggests that modification of the bone microenvironment does influence the clinical course of both early breast cancer and castrate-resistant prostate cancer, particularly in clinical settings in which bone metabolism is no longer primarily regulated by reproductive hormones.
  
  
  CONCLUSIONS
  The role of bisphosphonates in CTIBL in breast cancer is now defined, but in other malignancies more evidence is needed prior to recommendation as standard treatment. In the role of preventing metastasis, results of ongoing studies are awaited to help clarify populations of patients who will derive benefit. Alternative therapies including the RANKL inhibitor denosumab may provide an alternative adjuvant treatment strategy. Combination therapy with adjuvant bone-targeted agents is yet to be investigated.
authors.affiliation: Yorkshire Cancer Research Academic Unit of Clinical Oncology, Weston Park Hospital, Sheffield, UK.
authors.forename: C
authors.initials: C
authors.lastname: Wilson
authors.forename: R E
authors.initials: RE
authors.lastname: Coleman
mesh_terms: D000277:Adjuvants, Pharmaceutic / Q000627:therapeutic use; D000284:Administration, Oral; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000627:therapeutic use; D047072:Aromatase Inhibitors / Q000627:therapeutic use; D050071:Bone Density Conservation Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D000069448:Denosumab; D004164:Diphosphonates / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D010024:Osteoporosis / Q000139:chemically induced / Q000188:drug therapy*; D017697:Premenopause; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D053245:RANK Ligand / Q000627:therapeutic use
chemical_list: D000277:Adjuvants, Pharmaceutic; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D047072:Aromatase Inhibitors; D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D053245:RANK Ligand; D000069448:Denosumab