title: Levothyroxine dose and risk of fractures in older adults: nested case-control study.
abstract: OBJECTIVE
  To quantify the effect of levothyroxine dose on risk of fractures in older adults.
  
  
  METHODS
  Nested case-control study.
  
  
  METHODS
  Population based health databases, Ontario, Canada.
  
  
  METHODS
  Adults aged 70 or more prescribed levothyroxine between 1 April 2002 and 31 March 2007 and followed for fractures until 31 March 2008. Cases were cohort members admitted to hospital for any fracture, matched with up to five controls from within the cohort who had not yet had a fracture.
  
  
  METHODS
  Primary outcome was fracture (wrist or forearm, shoulder or upper arm, thoracic spine, lumbar spine and pelvis, hip or femur, or lower leg or ankle) in relation to levothyroxine use (current, recent past, remote). Risk among current users was compared between those prescribed high, medium, and low cumulative levothyroxine doses in the year before fracture.
  
  
  RESULTS
  Of 213,511 prevalent levothyroxine users identified, 22,236 (10.4%) experienced a fracture over a mean 3.8 years of follow-up, 18,108 (88%) of whom were women. Compared with remote levothyroxine use, current use was associated with a significantly higher risk of fracture (adjusted odds ratio 1.88, 95% confidence interval 1.71 to 2.05), despite adjustment for numerous risk factors. Among current users, high and medium cumulative doses (>0.093 mg/day and 0.044-0.093 mg/day) were associated with a significantly increased risk of fracture compared with low cumulative doses (<0.044 mg/day): 3.45 (3.27 to 3.65) and 2.62 (2.50 to 2.76), respectively.
  
  
  CONCLUSIONS
  Among adults aged 70 or more, current levothyroxine treatment was associated with a significantly increased risk of fracture, with a strong dose-response relation. Ongoing monitoring of levothyroxine dose is important to avoid overtreatment in this population.
authors.affiliation: Department of Medicine, University of Toronto, Canada.
authors.forename: Marci R
authors.initials: MR
authors.lastname: Turner
authors.forename: Ximena
authors.initials: X
authors.lastname: Camacho
authors.forename: Hadas D
authors.initials: HD
authors.lastname: Fischer
authors.forename: Peter C
authors.initials: PC
authors.lastname: Austin
authors.forename: Geoff M
authors.initials: GM
authors.lastname: Anderson
authors.forename: Paula A
authors.initials: PA
authors.lastname: Rochon
authors.forename: Lorraine L
authors.initials: LL
authors.lastname: Lipscombe
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D004305:Dose-Response Relationship, Drug; D005260:Female; D005500:Follow-Up Studies; D050723:Fractures, Bone / Q000139:chemically induced*; D006801:Humans; D007037:Hypothyroidism / Q000188:drug therapy*; D008297:Male; D012307:Risk Factors; D013974:Thyroxine / Q000008:administration & dosage / Q000009:adverse effects*
chemical_list: D013974:Thyroxine