title: Use of thiazolidinediones and the risk of elective hip or knee replacement: a population based case-control study.
abstract: OBJECTIVE
  Osteoarthritis (OA) is the most common musculoskeletal condition in the elderly population. However, no disease modifying drug exists for this disease. In vivo animal studies have suggested that thiazolidinediones (TZD) may be used as disease modifying osteoarthritis drugs (DMOADs). To our knowledge, this has not yet been examined in humans before. The aim was to determine the risk of total joint replacement (TJR) in patients using TZDs compared with diabetic patients using other antidiabetic drugs.
  
  
  METHODS
  A population based case-control study was performed using the Clinical Practice Research Datalink (CPRD). Cases (n = 94 609) were defined as patients >18 years of age who had undergone total knee (TKR) or hip replacement (THR) between 2000 and 2012. Controls were matched by age, gender and practice/surgery. Conditional logistic regression analyses were used to estimate the risk of TKR and THR with the use of TZDs in patients currently using one or more antidiabetic drugs. In order to determine effect with prolonged use, we also stratified TZD users by total number of prescriptions prior to surgery. We statistically adjusted our analyses for lifestyle factory, comorbidities and concomitant drug use.
  
  
  RESULTS
  There was no difference in risk of TKR (OR 1.09, 95% CI 0.93, 1.27) and THR (OR 0.92, 95% CI 0.76, 1.10) when TZD users were compared with other AD users. Furthermore, we did not find an association with prolonged use of TZDs and TJR.
  
  
  CONCLUSIONS
  Despite promising results from animal in vivo studies, this study did not find any evidence for a disease modifying osteoarthritic effect of TZDs.
authors.affiliation: Department of Pharmacoepidemiology & Clinical Pharmacology, Utrecht University, Utrecht.|Department of Epidemiology, CAPHRI School for Public Health and Primary Care, Maastricht University, Maastricht.
authors.forename: Johannes T H
authors.initials: JT
authors.lastname: Nielen
authors.affiliation: Department of Pharmacoepidemiology & Clinical Pharmacology, Utrecht University, Utrecht.|Department of Clinical Pharmacy and Toxicology, Maastricht University Medical Center, Maastricht.
authors.forename: Frank
authors.initials: F
authors.lastname: de Vries
authors.affiliation: Department of Epidemiology, CAPHRI School for Public Health and Primary Care, and CARIM School for Cardiovascular Diseases, Maastricht University, Maastricht.
authors.forename: Pieter C
authors.initials: PC
authors.lastname: Dagnelie
authors.affiliation: Department of Pharmacy, Sint Maartenskliniek, Nijmegen.|Department of Pharmacy, Radboud University Medical Center, Nijmegen.
authors.forename: Bart J F
authors.initials: BJ
authors.lastname: van den Bemt
authors.affiliation: Department of Orthopaedics, Maastricht University Medical Center, Maastricht.
authors.forename: Pieter J
authors.initials: PJ
authors.lastname: Emans
authors.affiliation: Department of Pharmacoepidemiology & Clinical Pharmacology, Utrecht University, Utrecht.|Department of Clinical Pharmacy, University Medical Center Utrecht, Utrecht.
authors.forename: Arief
authors.initials: A
authors.lastname: Lalmohamed
authors.affiliation: Department of Pharmacoepidemiology & Clinical Pharmacology, Utrecht University, Utrecht.
authors.forename: Anthonius
authors.initials: A
authors.lastname: de Boer
authors.affiliation: Department of Internal Medicine, Division of Rheumatology, Maastricht University Medical Center, Maastricht, the Netherlands.
authors.forename: Annelies
authors.initials: A
authors.lastname: Boonen
mesh_terms: D000368:Aged; D019644:Arthroplasty, Replacement, Hip / Q000706:statistics & numerical data*; D019645:Arthroplasty, Replacement, Knee / Q000706:statistics & numerical data*; D016022:Case-Control Studies; D003920:Diabetes Mellitus / Q000188:drug therapy; D017558:Elective Surgical Procedures; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D016015:Logistic Models; D008297:Male; D015207:Osteoarthritis, Hip / Q000150:complications / Q000188:drug therapy* / Q000601:surgery; D020370:Osteoarthritis, Knee / Q000150:complications / Q000188:drug therapy* / Q000601:surgery; D045162:Thiazolidinediones / Q000008:administration & dosage / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D007004:Hypoglycemic Agents; D045162:Thiazolidinediones
keywords: arthroplasty; diabetes mellitus; glitazones; osteoarthritis; thiazolidinediones