Varus malalignment negates the structure-modifying benefits of doxycycline in obese women with knee osteoarthritis

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.