title: Reduction of leucocyte telomere length in radiographic hand osteoarthritis: a population-based study.
abstract: BACKGROUND
  Although age is the strongest predictor of osteoarthritis, the exact mechanism underlying this disorder remains elusive.
  
  
  OBJECTIVE
  To examine the association between leucocyte telomere length (LTL), a bio-indicator of ageing, and radiographic hand osteoarthritis.
  
  
  METHODS
  An unselected, predominantly female sample from the TwinsUK Adult Twin Registry (Twin Research and Genetic Epidemiology Unit, St Thomas Hospital, London, UK) was studied. Radiographs of both hands were obtained with a standard posteroanterior view and assessed for radiographic osteoarthritis according to the Kellgren/Lawrence (K/L) score. Individual radiographic features including osteophytes and joint space narrowing (JSN) were also assessed on a four-point scale using a standard atlas. Hand osteoarthritis was defined radiographically as having >or=3 osteoarthritis-affected joints of both hands (K/L score>or=2). Severity of hand osteoarthritis was indicated semiquantitatively by total K/L scores, osteophytes, JSN scores and proportion of joints affected. Mean LTL was measured by the terminal restriction fragment length using the Southern blot.
  
  
  RESULTS
  A total of 1086 Caucasian subjects (mean (SD) age 55 (8.0) years) were studied. LTL was 6.95 (0.64) kb and was inversely correlated with age. After adjustment for age, sex, body mass index and smoking, LTL was significantly shorter by 178 bp in subjects with hand osteoarthritis (n = 160) than in those without (n = 926; p = 0.04). LTL was also significantly associated with semicontinuous measures of osteoarthritis (eg, total K/L score, JSN score, osteophyte score and proportion of joints affected) after adjustment (all p<or=0.02) in a dose-response fashion.
  
  
  CONCLUSIONS
  Shorter LTL equivalent to around 11 years of annual loss in normal people is associated with radiographic hand osteoarthritis and disease severity, suggesting potential shared mechanisms between osteoarthritis and ageing, and implicating oxidative stress and low-level chronic inflammation in both conditions.
authors.affiliation: Twin Research and Genetic Epidemiology Unit, St Thomas' Hospital, Lambeth Palace Road, London SE1 7EH, UK. guangju.zhai@kcl.ac.uk
authors.forename: G
authors.initials: G
authors.lastname: Zhai
authors.forename: A
authors.initials: A
authors.lastname: Aviv
authors.forename: D J
authors.initials: DJ
authors.lastname: Hunter
authors.forename: D J
authors.initials: DJ
authors.lastname: Hart
authors.forename: J P
authors.initials: JP
authors.lastname: Gardner
authors.forename: M
authors.initials: M
authors.lastname: Kimura
authors.forename: X
authors.initials: X
authors.lastname: Lu
authors.forename: A M
authors.initials: AM
authors.lastname: Valdes
authors.forename: T D
authors.initials: TD
authors.lastname: Spector
mesh_terms: D000328:Adult; D000368:Aged; D000375:Aging / Q000235:genetics; D004200:Diseases in Twins / Q000235:genetics*; D005260:Female; D050823:Hand Joints / Q000000981:diagnostic imaging*; D006801:Humans; D007962:Leukocytes / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D010003:Osteoarthritis / Q000000981:diagnostic imaging / Q000235:genetics*; D011859:Radiography; D012720:Severity of Illness Index; D016615:Telomere / Q000235:genetics*