Effects of doxycycline on progression of osteoarthritis: Results of a randomized, placebo‐controlled, double‐blind trial

OBJECTIVE: To confirm preclinical data suggesting that doxycycline can slow the progression of osteoarthritis (OA). The primary outcome measure was joint space narrowing (JSN) in the medial tibiofemoral compartment. METHODS: In this placebo-controlled trial, obese women (n = 431) ages 45-64 years with unilateral radiographic knee OA were randomly assigned to receive 30 months of treatment with 100 mg doxycycline or placebo twice a day. Tibiofemoral JSN was measured manually in fluoroscopically standardized radiographic examinations performed at baseline, 16 months, and 30 months. Severity of joint pain was recorded at 6-month intervals. RESULTS: Seventy-one percent of all randomized subjects completed the trial. Radiographs were obtained from 85% of all randomized subjects at 30 months. Adherence to the dosing regimen was 91.8% among subjects who completed the study per protocol. After 16 months of treatment, the mean +/- SD loss of joint space width in the index knee in the doxycycline group was 40% less than that in the placebo group (0.15 +/- 0.42 mm versus 0.24 +/- 0.54 mm); after 30 months, it was 33% less (0.30 +/- 0.60 mm versus 0.45 +/- 0.70 mm). Doxycycline did not reduce the mean severity of joint pain, although pain scores in both treatment groups were low at baseline and remained low throughout the trial, suggesting the presence of a floor effect. However, the frequency of followup visits at which the subject reported a > or = 20% increase in pain in the index knee, relative to the previous visit, was reduced among those receiving doxycycline. In contrast, doxycycline did not have an effect on either JSN or pain in the contralateral knee. In both treatment groups, subjects who reported a > or = 20% increase in knee pain at the majority of their followup visits had more rapid JSN than those whose pain did not increase. CONCLUSION: Doxycycline slowed the rate of JSN in knees with established OA. Its lack of effect on JSN in the contralateral knee suggests that pathogenetic mechanisms in that joint were different from those in the index knee.