Risedronate Retains Impact on OA Biomarkers : It remains to be seen whether changes in biomarkers will translate into clinical joint preservation.

So either improvement is part of the natural course of the disease or there is a clinical benefit simply in entering a clinical trial. Regardless, this effect needs to be taken into consideration in designing future osteoarthritis trials, said Dr. Bingham, who is also with the division of allergy and immunology at Johns Hopkins University.

In terms of structure, 13% of participants had radiographic progression. There were no statistically significant differences in any treatment group in either cohort.

“When you looked at the people who were showing what was unequivocally progression … there was no drug effect that was demonstrated but interestingly that group of people was only a very small percentage of the entire study population,” said Dr. Bingham.

The radiographic findings also have implications for future trial design: If only a small number of people are going to show substantial worsening in terms of joint structure, then—in order to study an OA drug by looking at structure as an outcome—greater numbers of patients are needed to be able to demonstrate a potential treatment effect, he said.

In both cohorts, a dose-dependent decrease in the level of NTX-I was observed within 6 months for those on risedronate, and it continued through 24 months. The mean percent change from baseline to 24 months for all dosages of risedronate was statistically different from the placebo group. In the North American group, those on placebo had a mean increase in NTX-I of 7.3%, whereas those on risedronate at dosages of 5 mg/day, 15 mg/day, and 50 mg/week had NTX-I level decreases of 21.6%, 39.2%, and 29.2%, respectively. In the European cohort, those on placebo had a mean increase in NTX-I of 3.0%, whereas those on risedronate at dosages of 5 mg/day, 15 mg/day, and 35 mg/week had NTX-I level decreases of 29.0%, 41.7%, and 28.2%, respectively.

The results for CTX-II levels were similar, with those on placebo having increases over 24 months, whereas those on risedronate had early decreases. At 15 mg/day risedronate, reductions of 17.9% and 19.6% from baseline were seen in North American and European patients respectively. In comparison, the North American and European placebo groups had increases of CTX-II levels of 26.3% and 10.1%, respectively.

The biomarker results suggest—from a pathobiologic perspective—that an agent that acts on subchondral bone, interrupts the turnover of bone, and improves bone structure can consequently improve cartilage stability. This suggests a fundamental interaction between bone and cartilage. This could be important because treatments already are available that interrupt bone turnover.

These study results indicate that “potentially the bone is an important therapeutic target in patients with osteoarthritis,” said Dr. Bingham.