Bisphosphonate Use May Prevent Radiographic Knee Osteoarthritis Progression

Radiograph of a knee with osteoarthritis
Radiograph of a knee with osteoarthritis
Researchers compared the 2-year radiographic progression of knee osteoarthritis between individuals who received vs did not receive bisphosphonates.

Bisphosphonate use may prevent radiographic knee osteoarthritis (OA) progression among women with risk factors for knee OA, according to study results published in the Journal of Bone and Mineral Research.

There are limited data on the protective role of nitrogen-containing oral bisphosphonates on radiographic progression of knee OA. The objective of the current study was to assess the effect of bisphosphonate use on radiographic progression of knee OA in participants enrolled in the Osteoarthritis Initiative (OAI), an open-source study of knee OA.

Researchers completed a propensity-matched retrospective cohort analysis of the OAI to examine the effects of bisphosphonate use on radiographic knee OA progression over 2 years.

Of 1977 women aged ≥50 years with available data, 346 reported use of bisphosphonates, including alendronate (69%), risedronate (19%), or others (12%), at baseline. Researchers propensity-matched 344 of the 346 bisphosphonate users with 344 nonusers.

Radiographic progression, defined by ≥1 Kellgren and Lawrence (KL) grade, was recorded in 95 (13.8%) participants over the 2-year follow-up period, of whom 27 patients had KL <2 (n=10 bisphosphonate users) and 68 had KL ≥2 (n=35 bisphosphonate users). Statistical analysis revealed the 2-year risk for progression was 10.5% and 5.9% for bisphosphonate nonusers and users, respectively, with a baseline KL grade of 0 or 1; risk for progression was 23.0% and 23.5% for nonusers and users, respectively, with a baseline KL grade of 2 or 3.

Bisphosphonate use had no significant effect on OA progression in women who had baseline evidence of radiographic knee OA (KL grade, ≥2); however, in early-stage women with a baseline KL grade <2, the risk for progression was significantly lower for patients who received bisphosphonates (hazard ratio [HR], 0.53; 95% CI, 0.35-0.79).

In addition, the protective effect of bisphosphonates was more significant in nonoverweight (body mass index [BMI], <25 kg/m2) early-stage (KL grade, <2) patients (HR, 0.49; 95% CI, 0.26-0.92; n=166 bisphosphonate users). However, for patients with a higher BMI, bisphosphonate use had no significant effect.

The study had several limitations including the relatively small sample size, potential selection bias, possible misclassification of radiographic outcomes results secondary to variation in radiologist assessment, and missing data on potential confounders.

“Treating individuals with knee OA and osteoporosis risk factors earlier could potentially mitigate more detrimental downstream structural effects on the knee and is particularly important to consider when individuals are nonoverweight,” concluded the researchers.


Hayes KN, Giannakeas V, Wong AKO. Bisphosphonate use is protective of radiographic knee osteoarthritis progression among those with low disease severity and being non-overweight: data from the Osteoarthritis Initiative [published online July 14, 2020]. J Bone Miner Res. doi:10.1002/jbmr.4133