title: The mechanism of the effect of obesity in knee osteoarthritis: the mediating role of malalignment.
abstract: OBJECTIVE
  Obesity is most strongly linked to osteoarthritis (OA) at the knee. Varus malalignment was examined as a possible local mediator that may increase the impact of body weight at the knee, versus the hip or ankle. Compartment load distribution is more equitable in valgus than in varus knees, and valgus knees may better tolerate obesity. We therefore tested whether 1) body mass index (BMI) is correlated with OA severity in varus knees, 2) the BMI-OA severity correlation is weaker in valgus than in varus knees, 3) BMI is correlated with the severity of varus malalignment, and 4) the BMI-medial tibiofemoral OA severity relationship is reduced after controlling for varus malalignment.
  
  
  METHODS
  In 300 community-recruited patients with knee OA, 2 groups (varus and valgus) were identified based on dominant knee alignment on a full-limb radiograph, i.e., the angle formed by the intersection of the femoral and tibial mechanical axes. Severity of knee OA was assessed by measurement of the narrowest joint space width on radiographs of knees in a fluoroscopy-confirmed semiflexed position.
  
  
  RESULTS
  Alignment direction was symmetric (or neutral in 1 limb) in 87% of patients. One hundred fifty-four patients had varus knees and 115 had valgus knees. BMI correlated with OA severity in the varus group (r = -0.29, P = 0.0009) but not in the valgus group (r = -0.13, P = 0.17). BMI correlated with malalignment in those with varus knees (r = 0.26) but not in those with valgus knees (r = 0.16). The partial correlation of BMI and OA severity, controlling for sex, was reduced from 0.24 (P = 0.002) to 0.04 (P = 0.42) when varus malalignment was added to the model.
  
  
  CONCLUSIONS
  BMI was related to OA severity in those with varus knees but not in those with valgus knees. Much of the effect of BMI on the severity of medial tibiofemoral OA was explained by varus malalignment, after controlling for sex. Whether it precedes or follows the onset of disease, varus malalignment is one local factor that may contribute to rendering the knee most vulnerable to the effects of obesity.
authors.affiliation: Division of Rheumatology, Northwestern University, Chicago, Illinois 60611, USA. l-sharma@nwu.edu
authors.forename: L
authors.initials: L
authors.lastname: Sharma
authors.forename: C
authors.initials: C
authors.lastname: Lou
authors.forename: S
authors.initials: S
authors.lastname: Cahue
authors.forename: D D
authors.initials: DD
authors.lastname: Dunlop
mesh_terms: D000368:Aged; D015992:Body Mass Index; D017760:Bone Malalignment / Q000503:physiopathology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000150:complications*; D020370:Osteoarthritis, Knee / Q000150:complications* / Q000000981:diagnostic imaging; D011859:Radiography; D012720:Severity of Illness Index