Zoledronic acid disappoints in ZAP2 knee osteoarthritis trial
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.
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