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

Abstract

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 >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 >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.In the present report, we describe the results of a randomized, placebo-controlled, double-blind trial of the tetracycline antibiotic, doxycycline, in subjects with knee osteoarthritis (OA). Selection of doxycycline as a potential disease-modifying OA drug was based not on the premise that OA is an infectious disease, but rather on results of in vitro studies showing 1) that doxycycline inhibited the degradation of type XI collagen, one of the minor collagens of articular cartilage, by 72-kd gelati-

The peroxisome proliferator–activated receptor γ agonist pioglitazone reduces the development of cartilage lesions in an experimental dog model of osteoarthritis: In vivo protective effects mediated through the inhibition of key signaling and catabolic pathways

“…The experimental dog model of ACLT-induced OA has been used extensively for such purposes (20,21,23,(25)(26)(27) and could thus be an exception and serve as a useful tool in the study of human OA. Studies have recently shown that the positive effects of doxycycline on OA structural changes in an experimental dog model of OA (28) could also be seen in patients with knee OA treated with this drug (29). These findings are interesting, but before any final judgment can be made, the results need to be further validated by confirmatory studies.…”

Persistence, Localization, and External Control of Transgene Expression After Single Injection of Adeno-Associated Virus into Injured Joints

“…It has a long-term record of relative safety and few recognized adverse effects, namely sun sensitivity, monilial vaginitis, and nonspecific gastrointestinal symptoms. In a human trial that used doxycycline for 30 months, only these three side effects were observed (Brandt et al, 2005). No serious adverse events, such as death, hospitalization, and development of a life-threatening or debilitating condition, were attributable to doxycycline.…”

Periodic knee injections of BMP‐7 delay cartilage degeneration induced by excessive running in rats

“…However, the effect of hyaluronan on prevention of OA seems to be limited according to several metaanalyses. 17 Recently, novel approaches such as injection of caspase inhibitors, 18 treatment with basic fibroblast growth factor, 19 oral doxycycline, 20 and oral glucosamine 21 have been reported for OA prevention. In our results, BMP-7 reduced OA progression but did not block progression of OA completely.…”