title: Clinical review: Effect of endocrine therapies on bone in breast cancer patients.
abstract: BACKGROUND
  Two common strategies are used to treat estrogen receptor-positive breast cancer in women: tamoxifen to inhibit estrogen action, and aromatase inhibitors (AIs) to block estrogen biosynthesis. Recent data suggest that AIs are more effective than tamoxifen in the adjuvant and advanced disease settings and are now being more commonly used. Tamoxifen, as a selective estrogen receptor modulator, exerts estrogenic effects to preserve bone, whereas the AIs profoundly lower estrogen levels and cause bone loss. Recent comparative studies of these agents provide extensive data on fracture rates, bone mineral density, and markers of bone formation and resorption.
  
  
  OBJECTIVE
  The aim of the study was to review the mechanistic effects of estrogen on bone and clinical data regarding bone density, bone turnover markers, and fracture rates in women with breast cancer taking tamoxifen or AIs.
  
  
  METHODS
  Data presented reflect a review of the literature and data integration from the perspective of the author's knowledge of the field.
  
  
  RESULTS
  Tamoxifen increases bone density and reduces fractures in postmenopausal women with breast cancer, whereas AIs increase rate of fracture, accelerate loss of bone mineral density, and enhance levels of markers of bone formation and resorption. Bisphosphonates and denosumab counteract the effects of the AIs on bone. Guidelines for management of AI-induced bone loss are available from several sources, but a simple algorithm guides decision making most effectively.
  
  
  CONCLUSIONS
  Endocrine therapy for postmenopausal women with breast cancer exerts substantial effects on bone, and guidelines are available to assist in the management of bone-related problems.
authors.affiliation: Division of Endocrinology and Metabolism, Department of Internal Medicine, University of Virginia Health Sciences System, Charlottesville, Virginia 22908-1416, USA. rjs5y@virginia.edu
authors.forename: R J
authors.initials: RJ
authors.lastname: Santen
mesh_terms: D000328:Adult; D000368:Aged; D018931:Antineoplastic Agents, Hormonal / Q000009:adverse effects / Q000627:therapeutic use*; D047072:Aromatase Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use*; D015519:Bone Density; D050071:Bone Density Conservation Agents / Q000627:therapeutic use; D001846:Bone Development / Q000187:drug effects; D001847:Bone Diseases / Q000139:chemically induced* / Q000188:drug therapy / Q000473:pathology; D001862:Bone Resorption / Q000139:chemically induced / Q000453:epidemiology; D001943:Breast Neoplasms / Q000150:complications* / Q000188:drug therapy* / Q000378:metabolism; D004965:Estrogen Antagonists / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D050723:Fractures, Bone / Q000453:epidemiology; D017408:Guidelines as Topic; D006801:Humans; D008875:Middle Aged; D053245:RANK Ligand / Q000276:immunology; D016032:Randomized Controlled Trials as Topic; D020845:Selective Estrogen Receptor Modulators / Q000627:therapeutic use; D013629:Tamoxifen / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D018931:Antineoplastic Agents, Hormonal; D047072:Aromatase Inhibitors; D050071:Bone Density Conservation Agents; D004965:Estrogen Antagonists; D053245:RANK Ligand; D020845:Selective Estrogen Receptor Modulators; D013629:Tamoxifen