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21-04-2020 | Rheumatology | News | Article

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Zoledronic acid disappoints in ZAP2 knee osteoarthritis trial

Author: Claire Barnard

medwireNews: Annual infusions of zoledronic acid do not reduce cartilage volume loss, pain, or bone marrow lesion size in people with knee osteoarthritis (OA), suggest findings from the phase 3 ZAP2 trial.

Graeme Jones (University of Tasmania, Hobart, Australia) and co-investigators report in JAMA that tibiofemoral cartilage volume decreased by an average of 878 mm3 from baseline to the 2-year follow-up among 113 bisphosphonate-naïve patients with knee OA and bone marrow lesions who were randomly assigned to receive a 15-minute intravenous infusion of zoledronic acid 5 mg at baseline and again at 1 year.

By comparison, the 110 participants who were instead assigned to receive placebo infusions experienced an average cartilage volume loss of 919 mm3, giving a nonsignificant between-group difference of 41 mm3.

Jones and team say that knee pain and bone marrow lesion size decreased in both groups over the study period, with no significant between-group differences. Specifically, the average WOMAC pain score decreased by 37.5 points from a baseline of 180.0 points in the zoledronic acid group, and by 58.0 points from a baseline of 219.9 points in the placebo arm. Mean bone marrow lesion size decreased by 33 mm2 and 6 mm2 in the zoledronic acid and placebo groups, respectively.

In all, 96% of participants given zoledronic acid and 83% of those given placebo experienced adverse events, with the between-group difference mainly attributed to a higher rate of acute reactions in the active treatment arm (87 vs 56%). The most frequently occurring acute reactions were musculoskeletal pain and stiffness (70 vs 30%), fever (52 vs 8%), and headache and dizziness (42 vs 26%).

The study authors report that rates of adverse events other than acute reactions were comparable in the zoledronic acid and control groups, at 68% and 67%, respectively, but knee replacement rates were higher in the active treatment arm, with corresponding rates of 9% and 2%.

“These findings do not support the use of zoledronic acid for slowing cartilage volume loss or alleviating knee pain in patients with knee osteoarthritis,” conclude the investigators.

medwireNews is an independent medical news service provided by Springer Healthcare. © 2020 Springer Healthcare part of the Springer Nature Group

JAMA 2020; 323: 1456–1466

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