Zoledronic Acid Infusions No Better Than Placebo For Knee Osteoarthritis

Dawn Aitken, PhD

Yearly zoledronic acid infusions were no better than placebo at significantly reducing cartilage volume loss over 24 months in patients with knee osteoarthritis, according to recent study findings.

The findings suggested that zoledronic acid should not be used to treat the condition.

Dawn Aitken, PhD, and a team of investigators conducted a 24-month multicenter, double-blind placebo-controlled randomized clinical trial at 4 sites in Australia to determine the effects of intravenous zoledronic acid on knee cartilage volume loss in patients with symptomatic knee osteoarthritis and bone marrow lesions.

Aitken, from the Menzies Institute for Medical Research, and the Australia- and Canada-based colleagues included patients >50 years old with knee pain (pain score >40 mm on a 100-mm visual analog scale) on most days during the last month, met the American College of Rheumatology criteria for symptomatic knee osteoarthritis, and had subchondral bone marrow lesion on an MRI. If a patient had 2 eligible knees, the 1 with the worst pain and mild joint space narrowing was selected.

Participants were randomized by a staff member at 1 of the 4 sites who was not involved with the study. Each patient was assigned 1:1 to receive a single 15-minute intravenous infusion of zoledronic acid (5 mg in a 100 mL saline solution) or identical placebo (100 mL saline solution) at baseline and at 12 months. The patients were followed up until 24 months.

The primary outcome was the change in tibiofemoral cartilage volume. Investigators measured the change using MRI over 24 months. Additional outcomes included the change in total bone marrow lesion size after 6 and 24 months; change in knee pain after 3, 6, 12, 18, and 24 months; and the Western Ontario and McMaster Universities Osteoarthritis Index pain score.

The team screened 408 participants and 223 were randomized to receive zoledronic acid (n=113) or placebo (n=110). Only 190 participants (85%) completed the trial.

The mean age of the patients was 62 years old and 52% were women. The mean value of knee pain scores was higher, and the cartilage volume was lower in the placebo group than the zoledronic acid cohort.

There was no significantly different change between the zoledronic acid and placebo groups over 24 months (-878 mm_­³ vs -919 mm³; between-group difference, 41 mm³; 95% CI, -79 to 161 mm³; P=.5).

For secondary outcomes, there were also no significant between-group differences, including knee pain assessed by visual analog scale (−11.5 in the zoledronic acid group vs −16.8 in the placebo group; between-group difference, 5.2; 95% CI, −2.3 to 12.8; P=.17) and changes in knee pain assess by the Western Ontario and McMaster Universities Osteoarthritis Index (−37.5 vs −58.0; between-group difference, 20.5; 95% CI, −11.2 to 52.2; P=.21) over 24 months.

There were also no significant differences between changes in bone marrow lesion size (−33 mm² vs −6 mm²; between-group difference, −27 mm²; 95% CI, −127 to 73 mm²; P=.6) over 24 months.

Patients in the zoledronic acid group had more adverse events than those in the placebo group (96% vs 83%), which consisted mostly of acute reactions.

Although previous research showed that zoledronic acid reduced knee pain and bone marrow lesion size in those with knee osteoarthritis after 6 months, the findings did not support the use of such treatment for slowing down volume loss over 24 months.

The study, “Effect of Intravenous Zoledronic Acid on Tibiofemoral Cartilage Volume Among Patients With Knee Osteoarthritis With Bone Marrow Lesions,” was published online in JAMA Rheumatology.