Doxycycline Shows Potential in Slowing OA

Doxycycline may slow progression of osteoarthritis (OA) of the knee, according to the results of a randomized, double-blind trial conducted by Brandt et al from the Indiana University School of Medicine in Indianapolis. Their findings were published in the July 2005 issue of Arthritis and Rheumatism.

Doxycycline is a tetracycline antibiotic commonly prescribed by medical doctors for certain infections and to treat acne. In particular, it is used to treat urinary tract infections, gum disease, and other bacterial infections such as gonorrhea and chlamydia. In addition, Doxycycline is sometimes prescribed for the treatment of Lyme disease.

The selection of doxycycline as a potential disease-modifying OA drug was based on the results of previous vitro studies. These studies demonstrated that doxycycline inhibited the degradation of type XI collagen, one of the minor collagens involved in the moving areas of the knee. The presence of doxycycline also inhibited messenger RNA for inducible nitric oxide synthase, an enzyme present in large quantities in OA cartilage, the activity of which causes inflammation.

In this most recent study, 431 obese women between 45 and 64 years with unilateral radiographic knee OA were randomized to receive 30 months of treatment with 100 mg of doxycycline or placebo twice daily. The researchers measured joint space narrowing (JSN) in the medial tibiofemoral compartment. Close-fluoroscopy examination was used to make these measurements manually. At six-month intervals, patients reported severity of joint pain. Of all randomized study subjects, 71% completed the trial and 85% underwent radiographic examination at 30 months. Compared with the placebo group, mean loss of joint space width in the index knee in the doxycycline group was 40% less after 16 months of treatment and 33% less after 30 months. Pain scores in both treatment groups were low at baseline and remained low during the trial. However, the frequency of follow-up visits during which the subject reported at least a 20% increase in pain in the index knee, compared with the previous visit, was lower in the doxycycline group.

In conclusion, the researchers found that in both treatment groups, study subjects who reported at least a 20% increase in knee pain at most follow-up visits had more rapid JSN than did those with stable pain. In effect, Doxycycline slowed the rate of JSN in index knees with OA but did not reduce pain or JSN in the contralateral knee, which suggests that pathogenetic mechanisms in that joint were different from those in the index knee.

Article References
http://my.webmd.com/content/Article/108/108753.htm?z=1728_00000_1000_tn_06, site accessed on 08/11/05

http://www.jri-oh.com/Knee_Articular.htm, site accessed on 08/11/05