# Zoledronic Acid in the Treatment of Primary Knee Osteoarthritis: A Randomized Clinical Trial

## TL;DR

Zoledronic acid reduces knee pain and improves quality of life in patients with osteoarthritis, with effects lasting up to six months.

## Contribution

This is the first randomized clinical trial to demonstrate that zoledronic acid effectively reduces pain and NSAID use in primary knee osteoarthritis.

## Key findings

- Zoledronic acid significantly improved pain, stiffness, and function compared to placebo at three and six months.
- NSAID use was significantly lower in the zoledronic acid group.
- Flu-like symptoms were common in the zoledronic acid group but resolved without complications.

## Abstract

Background

Pain in primary knee osteoarthritis (OA) is the most disabling symptom. Osteoclast-initiated subchondral bone resorption, marrow edema, and synovitis collectively contribute to pain. Reduction of osteoclast activity by bisphosphonate may be effective in reducing pain.

Objective

This study aims to assess the role of zoledronic acid (ZA) in reducing the pain of primary knee OA.

Methodology

This double-blind, parallel, placebo-controlled randomized clinical trial was conducted in the Bangabandhu Sheikh Mujib Medical University from January 2023 to December 2023. A total of 79 patients were randomly enrolled in the ZA group (n = 39) and placebo group (n = 40) after having given informed written consent. Each patient was infused with a single infusion of ZA or placebo. Baseline status was measured by three domains (pain, stiffness, and functional status) of the Bangla version of the Western Ontario and McMaster Universities Osteoarthritis Index scale (WOMAC), visual analog scale (VAS), and quality of life by the European Quality of Life-5 Dimensions-5 Levels (EQ-5D-5L). One patient in the ZA group refused to take an infusion.

Patients were followed up at the third and sixth months. During this period, they were allowed to take non-steroidal anti-inflammatory drugs (NSAIDs) on a requirement basis with documentation and advised to undergo non-pharmacological treatment like maintaining ideal body weight, joint protection, and exercise. At the end of the third and sixth months, outcome status was assessed by three domains (pain, stiffness, and functional status) of WOMAC, VAS, and quality of life by EQ-5D-5L. Four patients from the ZA group and one from the placebo group failed to complete follow-up. Finally, the outcome values of 74 patients were compared within and between groups at the end of the third and sixth months. A paired t-test and an independent sample t-test were applied to compare within and between groups. A P-value ≤ 0.05 was considered significant. The study procedure was explained to the patients. Privacy and confidentiality of subjects were maintained.

Results

The study's population was diverse, with an age range of 50-80 years. Sixty (72.5%) were women, and the most common occupations were homemakers (30, 77%) and retired individuals (5, 13%). Vitamin D deficiency was found in 28 (35.4%) subjects, and 30 (38%) had osteoporosis. Within both groups, there was a significant improvement after three months (WOMAC total, P = 0.000, and VAS, P = 0.001) and six months (WOMAC total, P = 0.000, and VAS, P = 0.001) and in comparison, of changes between groups, changes in the ZA group were significantly higher (WOMAC total, P = 0.000, and VAS, P = 0.000) after three and six months. NSAIDs use was considerably lower in the ZA group after three months (P = 0.018) and six months (P = 0.000). Flu-like symptoms were noted in 14 (37%) patients of the ZA group, and injection site reactions occurred in 5 (12.5%) patients of the placebo group and 2 (5.7 %) in the ZA group.

Conclusions

ZA reduces knee pain, stiffness, and NSAID use, and improves functional status and quality of life at three and six months after a single infusion. With its sustained efficacy and reduced NSAID requirements, this treatment offers a promising alternative for patients and inspires clinicians to explore new avenues in OA management.