Zoledronic Acid May Not Improve Knee Osteoarthritis-Related Pain, Function Long-Term

knee pain
knee pain
Zoledronic acid did not significantly reduce knee pain or bone marrow lesion size overall in patients with knee osteoarthritis over 24 months.
The following article is part of conference coverage from the European League Against Rheumatism (EULAR) Congress 2018 in Amsterdam, The Netherlands. Rheumatology Advisor’s staff will be reporting breaking news associated with research conducted by leading experts in rheumatology. Check back for the latest news from EULAR 2018.

Although research had indicated that a single infusion of zoledronic acid may alleviate knee osteoarthritis-related pain and reduce the size of associated bone marrow lesions at 6 months,1 these effects were not maintained at 24 months, according to a study presented at the European League Against Rheumatism (EULAR) Congress, held June 13 to 16, 2018, in Amsterdam, Netherlands.

In this multicenter, double-blind, placebo-controlled clinical trial, 223 patients (aged ≥50 years; mean age, 62.0±8.0 years; 52.5% women) who reported knee osteoarthritis-associated pain scores ≥40 mm on a 0-to-100 mm visual analog scale (VAS) and presenting with bone marrow lesions visible on magnetic resonance imaging (MRI) were randomly assigned to receive an annual infusion of zoledronic acid (5 mg in 100 mL) saline or placebo (100 mL saline).

Patients with severe knee OA, as indicated by grade 3 joint space narrowing on radiographic examination (using the Osteoarthritis Research Society International atlas), were not included in the study. Changes from baseline to 24 months in knee pain and function —  assessed with the VAS and the Western Ontario and McMasters Universities Osteoarthritis Index (WOMAC) — and changes in total knee bone marrow lesion size (assessed from 5 sites and evaluated using proton density-weighted MRI) were the study’s outcomes.

Across the cohort, baseline levels were as follows: knee pain assessed with WOMAC (0-500 scale), 200.0±105.0; knee function assessed with WOMAC (0-1700 scale), 656.9±352.9; knee pain assessed via VAS, 51.0±20.5; and median bone marrow lesion size, 489.6 mm2.  Two years after the initial infusion, outcomes were comparable in participants who had received zoledronic acid vs placebo: WOMAC-assessed knee pain: -37.5 vs -58.0, respectively; P =.205; VAS-assessed knee pain: -11.5 vs -16.8, respectively; P =.17; knee function: 134.9 vs -159.2, respectively; P =.65; and knee bone marrow lesion size: -33.5 mm2 vs -11.7 mm2, respectively; P =.68.

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In patients with no radiographic evidence of osteoarthritis (grade 0 joint space narrowing), zoledronic acid was found to improve knee function compared with placebo (-296.9 vs -78.5, respectively; P =.06). Zoledronic acid-related adverse events included musculoskeletal pain and stiffness, as well as flu-like symptoms.

Once-yearly infusion of [zoledronic acid] did not significantly reduce knee pain or [bone marrow lesion] size overall in [patients with knee osteoarthritis] over 24 months but may have symptomatic benefit in milder disease,” concluded the study authors.

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  1. Laslett LL, Doré DA, Quinn SJ, et al.  Zoledronic acid reduces knee pain and bone marrow lesions over 1 year: a randomised controlled trial. Ann Rheum Dis. 2012;71(8);1322-1328.
  2. Cai G, Aitken D, Laslett L, et al. A multicenter randomised controlled trial of zoledronic acid for osteoarthritis of the knee with bone marrow lesions. Ann Rheum Dis. 2018;77(Suppl 2):OP0016.