title: Aromatase inhibitor-related musculoskeletal symptoms: is preventing osteoporosis the key to eliminating these symptoms?
abstract: BACKGROUND
  Aromatase inhibitors (AIs) are an effective treatment for postmenopausal women with hormone receptor-positive breast cancer. However, patients receiving AIs report a higher incidence of musculoskeletal symptoms and bone fractures; the mechanism and risk factors for this correlation are not well studied. The aim of this study was to correlate these musculoskeletal symptoms and bone fractures in patients receiving AIs with bone mineral density (BMD), previous tamoxifen use, and administration of calcium/bisphosphonate (Ca/Bis).
  
  
  METHODS
  We reviewed charts of 856 patients with hormone receptor-positive nonmetastatic breast cancer seen at our institution between January 1999 and October 2007. A total of 316 patients met the inclusion criteria of treatment with one of the AIs for > or = 3 months and availability of a dualenergy X-ray absorptiometry (DEXA) during this treatment. Arthralgia, generalized bone pain and/or myalgia, bone fracture after beginning AIs, any tamoxifen treatment, and Ca/Bis therapy were recorded.
  
  
  RESULTS
  Our study demonstrates a significant association between symptoms and DEXA-BMD results (P < .001). Similarly, the group receiving tamoxifen before AIs had fewer patients with arthralgia or generalized bone pain/myalgia or bone fracture (P < .001). Furthermore, the group receiving AIs plus Ca/Bis had more patients without musculoskeletal symptoms and had fewer fractures. Finally, the group receiving steroidal AIs compared with nonsteroidal AIs had more patients with arthralgia or generalized bone pain and/or myalgia, and bone fractures (P < .001).
  
  
  CONCLUSIONS
  Patients on AIs who develop osteoporosis are at increased risk of musculoskeletal symptoms and bone fracture. Comedication with Ca/Bis reduces the likelihood for osteoporosis and musculoskeletal symptoms. Patients who received tamoxifen before AIs were less likely to develop AI-related musculoskeletal symptoms. We recommend that patients on AIs should be offered Ca/Bis to reduce the incidence of musculoskeletal symptoms and fracture, especially if patients are receiving steroidal AI and/or did not receive tamoxifen before AIs.
authors.affiliation: Division of Clinical and Molecular Endocrinology, Cleveland Clinic Cancer, Cleveland, OH, USA. alaf73@yahoo.com
authors.forename: Alaa A
authors.initials: AA
authors.lastname: Muslimani
authors.forename: Timothy P
authors.initials: TP
authors.lastname: Spiro
authors.forename: Asif A
authors.initials: AA
authors.lastname: Chaudhry
authors.forename: Harris C
authors.initials: HC
authors.lastname: Taylor
authors.forename: Ishmael
authors.initials: I
authors.lastname: Jaiyesimi
authors.forename: Hamed A
authors.initials: HA
authors.lastname: Daw
mesh_terms: D015502:Absorptiometry, Photon; D000368:Aged; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use; D047072:Aromatase Inhibitors / Q000009:adverse effects*; D015519:Bone Density / Q000187:drug effects; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D002130:Calcium Phosphates / Q000008:administration & dosage; D004164:Diphosphonates / Q000008:administration & dosage; D005260:Female; D006801:Humans; D008875:Middle Aged; D009140:Musculoskeletal Diseases / Q000139:chemically induced*; D010024:Osteoporosis / Q000517:prevention & control*; D012189:Retrospective Studies; D013629:Tamoxifen / Q000627:therapeutic use
chemical_list: D018931:Antineoplastic Agents, Hormonal; D047072:Aromatase Inhibitors; D002130:Calcium Phosphates; D004164:Diphosphonates; D013629:Tamoxifen; C020243:calcium phosphate