title: Varus malalignment negates the structure-modifying benefits of doxycycline in obese women with knee osteoarthritis.
abstract: OBJECTIVE
  To estimate the extent to which varus malalignment, a source of abnormal intra-articular stresses in the medial tibiofemoral compartment and risk factor for progression of knee osteoarthritis (OA), may have diminished the structure-modifying benefit of doxycycline in knee OA.
  
  
  METHODS
  Post hoc treatment group comparisons from a randomized, placebo-controlled trial of the effect of doxycycline (100mg, twice daily) on medial joint space narrowing (JSN) in subgroups of varus and non-varus OA knees. Subjects (N=379 with X-ray follow-up) were obese 45-64-year-old women with unilateral knee OA at baseline. JSN was measured manually in semiflexed anteroposterior (AP) radiographs acquired with standardized fluoroscopic positioning. The anatomic-axis angle (AAA) was measured in each baseline radiograph and transformed to an estimate of the mechanical-axis angle (MAA(est)) using a validated regression equation. Knees with MAA(est)<178 degrees were classified as varus.
  
  
  RESULTS
  In our original comparison with placebo, doxycycline slowed the rate of medial JSN in OA knees by 38% at 16 months and by 33% at 30 months. Among non-varus OA knees, 16-month JSN in the doxycycline group was 44% slower than in the placebo group (0.09 vs 0.16 mm/year, P=0.080), and 39% slower at month 30 (0.10 vs 0.17 mm/year, P=0.026). JSN in varus knees (0.20-0.27 mm/year) was more rapid than in non-varus knees (P=0.083) and unaffected by doxycycline.
  
  
  CONCLUSIONS
  Varus malalignment negated the slowing of structural progression of medial-compartment OA by doxycycline. To our knowledge, this is the first report documenting that static varus angulation can negate a pharmacologic structure-modifying effect.
authors.affiliation: Indiana University School of Medicine, Indianapolis, IN, USA. smazzuca@iupui.edu
authors.forename: S A
authors.initials: SA
authors.lastname: Mazzuca
authors.forename: K D
authors.initials: KD
authors.lastname: Brandt
authors.forename: R
authors.initials: R
authors.lastname: Chakr
authors.forename: K A
authors.initials: KA
authors.lastname: Lane
mesh_terms: D000890:Anti-Infective Agents / Q000627:therapeutic use*; D017760:Bone Malalignment / Q000503:physiopathology*; D018450:Disease Progression; D004318:Doxycycline / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007719:Knee Joint / Q000187:drug effects*; D008875:Middle Aged; D009765:Obesity / Q000150:complications*; D020370:Osteoarthritis, Knee / Q000188:drug therapy* / Q000503:physiopathology; D012720:Severity of Illness Index; D016896:Treatment Outcome
chemical_list: D000890:Anti-Infective Agents; D004318:Doxycycline