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.

Conclusion: 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.

Figure 1

Mean rate (± SE) of medial-compartment joint space narrowing (JSN) over 30 months in varus, neutral and valgus knees: comparisons of knees treated with doxycycline and placebo. For varus, neutral and valgus knees, N’s in the doxycycline treatment group were 35, 37 and 109, respectively. For the placebo arm of the RCT, the corresponding N’s were 42, 49 and 89, respectively).