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Bisphosphonates for Knee Osteoarthritis: A Bone of Contention

The increasing prevalence of knee OA heightens the urgency of the search for effective therapies.

Key points
• Bisphosphonates do not decrease pain, improve function, or prevent radiographic progression of knee osteoarthritis when compared with placebo.

• Bisphosphonates may be helpful in the early osteoresorptive phase of osteoarthritis, but further study is needed.

• Bisphosphonates may also be helpful in patients with high levels of bone turnover.

Knee osteoarthritis is the most common form of osteoarthritis in the United States, affecting as many as 14 million adults. Vaysbrot and colleagues1 at Tufts Medical Center in Boston point out that with increasing prevalence and earlier presentation, finding effective therapies for knee osteoarthritis is of high importance.

A key feature of osteoarthritis is abnormal subchondral bone remodeling. The balance between resorption of bone and reformation can be altered in the setting of mechanical stress, with inflammation leading to imbalance in the direction of resorption over growth. Bisphosphonates have been proposed as disease-modifying drugs in osteoarthritis and are used for fracture prevention because of their inhibition of bone resorption.

The researchers sought to determine whether bisphosphonates had any benefit over placebo in knee osteoarthritis. They recently presented their findings in Osteoarthritis and Cartilage.

The study
The researchers conducted a systematic review and meta-analysis of randomized, controlled trials that looked at bisphosphonates and their effect on pain, function, radiographic progression, serious adverse effects, and gastrointestinal adverse events in patients with knee osteoarthritis. Ultimately, 7 studies were included in their analysis.

The results
• The researchers found the overall quality of the studies to be moderate to low.

• The mean change in pain from baseline to study end was not statistically different between those taking bisphosphonates and placebo (standard mean difference [SMD] = -0.16; 95% confidence interval [CI]: -0.34, 0.02).

• Function scores were not significantly different between those taking bisphosphonates verses those on placebo (SMD = -0.02; 95% CI: -0.11, 0.06).

• After 2 years, there was no difference in radiographic progression of knee osteoarthritis in those taking bisphosphonates versus those taking placebo (relative risk (RR) = 0.98; 95% CI: 0.77, 1.26).

• There was no significant difference in serious adverse events between patients with knee osteoarthritis taking bisphosphonates versus those taking placebo (RR = 1.83; 95% CI: 0.38, 8.75).

• There was no significant difference between groups with regards to discontinuation of treatment (RR = 0.88; 95% CI: 0.70, 1.12).

• There was no statistically significant difference in gastrointestinal events between groups (RR = 1.04; 95% CI: 0.87, 1.24).

Implications for clinicians
• There is no compelling evidence to suggest that treating patients with knee osteoarthritis with bisphosphonates will improve their comfort or functioning or reduce the progression of their disease.

• There may be some benefit to prescribing bisphosphonates for those with early knee osteoarthritis, but more study is needed.

• If you choose to prescribe bisphosphonates, you may reassure your patients that adverse effects are no more common than among those taking a placebo.


1. Vaysbrot EE, Osani MC, Musetti MC, et al. Are bisphosphonates efficacious in knee osteoarthritis? A meta-analysis of randomized controlled trials. Osteoarthritis Cartilage. 2018;26:154-164. https://doi.org/10.1016/j.joca.2017.11.013