A strong association between chondrocalcinosis, resulting from calcium pyrophosphate dihydrate (CPPD) deposition, and knee osteoarthritis (OA) is firmly established. However, despite the association, a causative pathogenic role for CPPD crystals on the progression of articular degeneration in the knee has not been definitively demonstrated. Here, Neogi et al (Arthritis Rheum 2006; 56(6): 1822) investigate the effect of chondrocalcinosis on the progression of knee OA using magnetic resonance imaging (MRI).
Subjects derived from two cohort studies, the Boston OA Knee Study (BOKS) and the Health Aging and Body Composition Study (Health ABC). BOKS enrolled male and female veterans with symptomatic knee OA. Health ABC enrolled functioning 70 – 79 years olds, of who those with radiographic knee OA were invited to participate. Subjects underwent plain radiography of the knees for grading of knee OA (by the Kelgren/Lawrence method) and the presence or absence of chondrocalcinosis. Radiographic acquisition technique differed by cohort. Subjects in BOKS underwent knee MRI at baseline and at 15 and 30 months. Subjects in Health ABC underwent knee MRI at baseline and three years. MR studies were evaluated for cartilage pathology using the Whole-Organ Magnetic Resonance Imaging Score (WORMS) method and read unblinded to sequence in BOKS, but blinded to sequence in Health ABC.
265 subjects (265 knees) from BOKS and 230 subjects (373 knees) from Health ABC were included in the analysis. Compared to Health ABC, subjects in BOKS were younger (67 vs. 74 years of age), with a greater proportion of males (58% vs. 31%), Caucasians (88% vs. 49%), and a higher mean body mass index (BMI) (31.5 vs. 29.5). Baseline chondrocalcinosis was more frequent in Health ABC compared to BOKS (18.5% vs. 9%, respectively). Baseline meniscal damage was detected in 34% of knees in BOKS and 28% of knees in Health ABC.
In BOKS, baseline knee chondrocalcinosis was associated with a decreased risk of progressive cartilage loss compared to knees without chondrocalcinosis after adjusting for age, gender, BMI and the presence of damaged menisci (RR 0.40 (95% CI 0.2 – 0.7)). This protective affect was noted in analyses of subjects with both damaged and intact menisci. Chondrocalcinosis was not significantly positively or negatively associated with progressive knee cartilage damage in Health ABC, including in subanalyses stratified by baseline meniscal damage.
Chondrocalcinosis was not associated with progressive cartilage damage in knees with baseline OA, but may be associated with a reduced risk of progressive damage in some populations.
Age is associated with both chondrocalcinosis and knee OA, and is a potential confounder of the relationship of chondrocalcinosis to knee OA. Cross sectional studies are incapable of reliably establishing causal relationships between exposures and outcomes and previous prospective studies examining the chondrocalcinosis/knee OA relationship have used radiographic techniques lacking sufficient sensitivity to yield convincing conclusions. This study is the best, to date, and elegantly shows a lack of association between chondrocalcinosis and progression of knee cartilage damage. The protective effect is interesting, but not consistent across the two cohorts examined. The discrepancy may be related to fundamental differences in the two cohorts, selection of subjects, or in differences in data acquisition and analysis. Regardless, the findings are compelling and deserve additional investigation into the mechanistic basis of the potential protective effect. Chondrocalcinosis is also associated with osteophyte formation, and this may exhibit effects on knee pain and function independent of cartilage damage, an issue not addressed by this investigation. In addition, further study is needed to establish the role of chondrocalcinosis in the initiation of knee OA, in which it may exhibit differing effects compared to those who already have OA.
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