BALTIMORE, Maryland—The bisphosphonate residronate (Actonel®; Procter & Gamble/sanofi-aventis) did not produce the hoped for slowing of osteoarthritis (OA) progression in placebo-controlled trials but did decrease some biochemical markers of cartilage degradation. Clifton O. Bingham, III, MD, et al, report results of the 2-year multinational Knee Osteoarthritis Structural Arthritis (KOSTAR) study in Arthritis & Rheumatism.¹

"Although risedronate (compared with placebo) did not improve signs or symptoms of OA, nor did it alter progression of OA, a reduction in the level of a marker of cartilage degradation was observed. A sustained clinically relevant improvement in signs and symptoms was observed in all treatment and placebo groups," writes Dr. Bingham, of the division of rheumatology and allergy and clinical immunology at Johns Hopkins University in Baltimore, Maryland.

2000-Patient Study Compared Risedronate to Placebo

The study included 2483 patients with medial compartment knee OA and 2–4 mm of joint space width (JSW). The patients were enrolled in two parallel 2-year studies in North America and Europe. They were randomized to efficacy of a range of risedronate doses (5 mg/day, 15 mg/day, 35 mg/week, 50 mg/week) with placebo. Outcomes were measured by the Western Ontario and MacMaster (WOMAC) universities osteoarthritis index and by the patient global assessment (PGA) scores, in addition to fluoroscopically positioned, semiflexed-view radiography.

The investigators found that all groups of patients had reductions of about 20% in WOMAC and PGA scores, with no significant differences among treatment groups or treatment vs placebo groups. They also found that risedronate did not significantly reduce radiographic progression, whether measured by decreased JSW or by a dichotomous definition of progression (joint space loss of  >e;0.6mm).

There was, however, a dose-dependent reduction in the level of the cartilage degradation marker C-terminal crosslinking telepeptide of type II (CTX-II) collagen in the risedronate-treated patients. "Whether a long-term reduction in the level of CTX-II would translate into a slower rate of progression could not be determined from the current study, due to the limited time period," the authors write.

CTX-II Findings Intriguing, but Clinical Import Unclear

David T. Felson, MD, of the clinical epidemiology unit at Boston University School of Medicine, in Massachusetts, told CIAOMed that the CTX-II finding is intriguing, although its clinical import is unclear. "CTX-II is probably a measure of cartilage degradation, and since residronate affected CTX-II, there is some evidence, perhaps, that risidronate affects cartilage breakdown. In this study, the most important findings are that risidronate had no effect on pain compared to placebo (the placebo group actually did slightly better than the risedronate group). There was also no effect on radiographic progression in the affected knee, so risidronate does not cause a detectable clinically important effect on cartilage loss."

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