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Calcium crystal deposition may be a risk factor for knee osteoarthritis (OA), according to a new study.

In an analysis including more than 6400 middle-aged to older adults, individuals with knee chondrocalcinosis were 75% more likely to develop knee OA than those without the condition at baseline.

Because knee chondrocalcinosis and OA are often observed together, it is commonly considered a feature of the OA disease process, said Jean W. Liew, MD, an assistant professor of rheumatology at Boston University, Boston, and coauthor of the study.

“This study suggests that calcium crystal deposition is a cause of knee OA rather than just a consequence,” she told Medscape Medical News.

The analysis included data from two independent cohorts: the Rotterdam Study (RS) and the Multicenter Osteoarthritis Study (MOST). RS enrolled individuals aged 55 years or older residing in Rotterdam, the Netherlands. MOST, which recruited participants from Birmingham, Alabama, and Iowa City, Iowa, enrolled adults aged 50-79 years with preexisting knee OA or at increased risk for OA due to overweight status, knee injury, or knee symptoms.

Researchers examined the association between baseline knee chondrocalcinosis, measured via x-ray, and development of radiographic knee OA over time. Radiographic knee OA was defined as a Kellgren and Lawrence grade (KLG) ≥ 2 or if the individual had undergone knee replacement at follow-up.

The analysis, published online on August 5, 2025, in Annals of the Rheumatic Diseases, included 3737 individuals from the RS cohort and 2750 individuals from the MOST cohort. At baseline in the RS cohort, 76.1% of participants had no signs of radiographic knee OA (KLG = 0), and 4.3% had knee chondrocalcinosis. For the MOST cohort, 68.5% had no signs of radiographic knee OA, and 5.0% had knee chondrocalcinosis at baseline.

The analysis found that knee chondrocalcinosis increased the risk for incident radiographic knee OA after adjustment for age, sex, and BMI. The pooled odds ratio (OR) between both groups was 1.75 (95% CI, 1.25-2.27; P < .001). There were no cases of regression of chondrocalcinosis during follow-up, which suggests that chondrocalcinosis does not resolve over time, Liew and colleagues wrote.

In a subgroup analysis including only individuals with KLG of 0 at baseline, the results were similar (OR = 1.77; 95% CI, 1.04-3.01; P = .035). More severe chondrocalcinosis was also associated with increased risk of developing knee OA.

Commenting on the study for Medscape Medical News, Sara Tedeschi, MD, MPH, noted that these findings “strongly suggest that [chondrocalcinosis] is a risk factor for the new development of osteoarthritis in people who don’t currently have radiographic osteoarthritis.”

Tedeschi is the head of crystal-induced arthritic diseases at Brigham and Women’s Hospital in Boston.

“One of the unique features of this paper,” she said, “is that they were able to look at knees that had chondrocalcinosis at baseline but no osteoarthritis at baseline and were able to follow them forward” with years of follow-up data.

Treatment Options

Liew now wants to explore whether treatments for inflammation related to calcium crystal deposition could also help prevent or delay progression of OA in this subset of patients.

“It’s time to look at designing studies focused on this subgroup of people (with chondrocalcinosis on imaging) and testing whether treatments that work for crystal-associated arthritis like gout or calcium pyrophosphate deposition disease would also work for knee OA,” she said.

“Hints of such benefits have appeared in previous cardiovascular randomized controlled trials of colchicine, where patients receiving the drug had a lower risk of joint replacement as a secondary outcome,” noted Tedeschi.

It’s “one interesting therapy to consider” for potential future trials, as are other anti-inflammatory medications like interleukin-1 inhibitors, she added.

This research was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Tedeschi has worked as a consultant for Merck, Avalo Therapeutics, and Amgen. Liew reported having no relevant disclosures.