title: Aromatase inhibitors associated with knee subchondral bone expansion without cartilage loss.
abstract: BACKGROUND
  The profound estrogen depletion caused by aromatase inhibitors (AIs) is associated with musculoskeletal symptoms, but the underlying pathophysiology remains unclear.
  
  
  OBJECTIVE
  To assess the effects of AI therapy on structural changes in knee cartilage and subchondral bone over 2 years in postmenopausal women. Setting and participants Thirty women with breast cancer, mean age 58.5 (standard deviation ± 5.6) years and 62 healthy controls, mean age 56.5 (standard deviation ± 4.6) years.
  
  
  METHODS
  Annualized changes in tibial cartilage volume and subchondral bone area, and worsening of tibiofemoral cartilage defects from paired knee magnetic resonance imaging 2 years apart were compared between the two groups.
  
  
  RESULTS
  The AI-treated women had significantly greater expansion of the tibial plateau than the control group. The mean annualized differences, after adjusting for age, body mass index and baseline bone area, were 22.1 mm(2) (95% confidence interval (CI) 7.6-36.6, p = 0.003) for the medial tibial plateau and 19.1 mm(2) (95% CI 9.6-28.5, p < 0.001) for the lateral tibial plateau. The annual change in tibial cartilage volume and the worsening of cartilage defects did not differ between women taking AI therapy and controls.
  
  
  CONCLUSIONS
  AI therapy is associated with knee subchondral bone expansion knee with no effect on knee cartilage in postmenopausal women without pre-existing joint symptoms. This suggests the effect of severe estrogen depletion on knee is on bone, with the tibial bone expansion most likely a response to mechanical load in the setting of bone loss. Whether this then results in an increased risk of knee osteoarthritis will need to be determined.
authors.affiliation: School of Public Health and Preventive Medicine, Monash University , Melbourne , Victoria.
authors.forename: S R
authors.initials: SR
authors.lastname: Davis
authors.forename: R J
authors.initials: RJ
authors.lastname: Bell
authors.forename: Y
authors.initials: Y
authors.lastname: Wang
authors.forename: F
authors.initials: F
authors.lastname: Hanna
authors.forename: M
authors.initials: M
authors.lastname: Davies-Tuck
authors.forename: R
authors.initials: R
authors.lastname: Bell
authors.forename: J
authors.initials: J
authors.lastname: Chirgwin
authors.forename: F
authors.initials: F
authors.lastname: Cicuttini
mesh_terms: D000077384:Anastrozole; D047072:Aromatase Inhibitors / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy*; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D000077289:Letrozole; D008279:Magnetic Resonance Imaging; D008592:Menisci, Tibial / Q000033:anatomy & histology / Q000187:drug effects*; D008875:Middle Aged; D009570:Nitriles / Q000494:pharmacology; D017698:Postmenopause; D011446:Prospective Studies; D013977:Tibia / Q000187:drug effects* / Q000473:pathology; D014230:Triazoles / Q000494:pharmacology
chemical_list: D047072:Aromatase Inhibitors; D009570:Nitriles; D014230:Triazoles; D000077384:Anastrozole; D000077289:Letrozole