Diacerein

PHILADELPHIA -- Numerous interventions are showing promise for altering the course of osteoarthritis, Dr. Sharon Kolasinski reported at a rheumatology update sponsored by the University of Pennsylvania.

Exercise and weight loss have repeatedly been shown to be helpful in patients with this disease, and the findings of recent trials confirm their benefits. Findings from the Observational Arthritis Study in Seniors (OASIS) trial published last year, for example, showed that improving knee strength may reduce knee pain and disability, said Dr. Kolasinski, chief of clinical services in the division of rheumatology at the university.

In two other studies, supervised exercise and weight loss programs resulted in significant reduction in pain and disability scores. Western Ontario and McMaster Universities (WOMAC) pain scores improved by 55% in one study and by 44% in another, while WOMAC disability scores decreased by more than 20%, she said at the meeting, which was also sponsored by the Department of Veterans Affairs.

In addition to these straightforward measures for intervening in osteoarthritis, Dr. Kolasinski discussed several interventions that target cartilage or bone and might also be of benefit:

* Vitamin C. Framingham data revealed that this antioxidant doesn't protect against OA, but it does appear to slow progression. In a comparison of 453 normal volunteers and 187 OA patients, high intake was associated with a threefold decrease in progression of disease.

* Glucosamine/Chondroitin. Metaanalyses suggest that the use of these supplements provides short-term analgesic benefit in OA patients with an effect comparable to that seen with NSAIDs. But the effect, which occurs in about 60% of patients, is delayed. Glucosamine and chondroitin tend to provide benefit in about 2 weeks, while NSAIDS provide benefit in 17 days.

In larger, high-quality studies, the benefit appears to be somewhat smaller than in less well-designed studies. Studies in animals are showing that glucosamine is bioavailable to chondrocytes in joint cartilage, and that it may indeed be disease modifying, Dr. Kolasinski said.

In a double-blind, randomized, controlled trial of 212 patients, 1,500 mg/day of glucosamine appeared to have a small effect on joint space narrowing: 15% of patients in the glucosamine group had joint space narrowing greater than 0.5 mm during the 3-year study period, compared with 30% of those in the control group.

* Diacerein. This anthraquinone has been shown in animal studies to decrease tissue damage, and in human studies to reduce pain and functional impairment in patients with knee and/or hip OA. In a study of 269 patients published last year, patients taking 50 mg b.i.d. of diacerein had less radiographic progression of disease than those taking placebo. Joint space narrowing of 0.5 mm or more occurred in 50.7% of the diacerein patients, compared with 60.4% of those taking placebo.

Diarrhea was a common side effect of the drug, occurring in 46% of patients, compared with 12% of patients in the placebo group.

* Doxycycline. This drug has been shown to have in vitro activity against collagenase and gelatinase, and in animal studies it reduced the severity of OA. Human studies are underway.

* Avocado/Soybean Unsaponifiables. In one randomized, controlled study this supplement was associated with a significant decrease in pain, functional disability, and NSAID dose in OA patients over a 6-month period. Side effects were minimal and comparable to placebo. In another study published in March, the supplement (300 mg once daily) reduced joint space loss by half over a 2-year period, compared with placebo, in patients with joint space width below the median, suggesting this treatment is most useful in patients with milder disease. The mean joint space loss in the treatment group was 0.43 mm, compared with 0.86 mm in the placebo group, Dr. Kolasinski said.

* Vitamin D. Framingham data show that low vitamin D intake and low serum vitamin D levels are associated with three times the risk of progression of knee OA, based on joint space narrowing.

The vitamin, which is known to affect bone rather than cartilage, does not appear to prevent OA in normal knees.

* Risedronate. This is another agent that may have a beneficial effect on bone. An ongoing Proctor & Gamble study is testing the hypothesis that strengthening subchondral bone with risedronate will slow OA progression. In previous studies, the drug was shown to decrease degradation fragments of type II collagen.

"Even though we tend to think of OA as a fairly intransigent disease, we can alter some aspects of the course of the disease. Pain and function can be altered by many of these interventions, and we may even be able to modify the need for surgery by aggressively managing our patients," Dr. Kolasinski said, adding that current research suggests that in the future it may even be possible to modify the pathogenetic mechanisms of the disease.

COPYRIGHT 2002 International Medical News Group
COPYRIGHT 2002 Gale Group