Purpose: Knee osteoarthritis (KOA) is a common disease where easily applicable, well-defined and objective tools for monitoring clinical improvement following treatment are not clearly defined; biomarkers could be such a tool. Weight loss is a recommended treatment for obese KOA patients, and short-term assessment of cartilage degradation is important. The aim of this study was to follow changes in cartilage markers Serum Cartilage Oligomeric Matrix Protein (S-COMP) and urine C-terminal telopeptide of collagen type II (U-CTX- II), and bone marker urine C-terminal telopeptide of collagen type I (U-CTX-I), over 16 weeks intensive weight loss in KOA patients.
Methods: 192 subjects from the outpatient clinic at Department of Rheumatology, Frederiksberg Hospital, Denmark were exposed to 16 weeks of weight loss (the CAROT study). Patients were over 50 years of age with a body mass index ≥ 30 kg/m2, and confirmed KOA on standing semi-flexed radiographs. S-COMP, U-CTX-II and U-CTX-I were determined by ELISA. To assess the symptomatic improvement, the change from baseline to 16 weeks in the average score on four subscales of the Knee Injury and Osteoarthritis Outcome Score (KOOS) _ pain, symptoms, function, and knee-related quality of life (KOOS4; range of scores, 0 [worst] to 100[best]). The statistical analysis was based on a general linear model, applying Analysis of Covariance (ANCOVA) with a factor for sex, with BMI and age at baseline both applied as covariates. To assess the bivariate association between each of the biomarkers with changes in body weight and KOOS4, Pearson Correlation Coefficients applied with a P-value ≤0.05 (two-tailed) indicating statistical significance.
Results: 91% (175) of the patients completed the 16 weeks weight loss scheme. The mean weight loss was 13.4 kg (95%CI: 12.5 to 14.4, P< .0001), mean loss of fat mass 11.2 kg (10.4 to 11.9, P<.0001), and maybe a small (non-significant) loss in lean body mass (0.7 kg; P=.089). By self-assessment, the patients showed a significant improvement of 10.0 on KOOS-4 (7.7 to 12.3, P<.0001). Looking at biomarkers at the group level, S-COMP decreased significantly with a mean of 1.1 U/l (0.7 to 1.5, P<.0001), while U-CTX-II increased with a mean of 63 ng/mmol creatine (25 to 101, P=.0013), and U-CTX-I increased with a mean of 66 μg/mmol creatine (46 to 86, P<.0001). On the individual participant level, change in S-COMP was correlated to weight change, with a decrease in S-COMP with decreased weight (r=-.16, P=.03), while U-CTX-II showed no correlation to weight loss (r=.11, P=.16). U-CTX-I increased with weight loss (r=.22, P=.0048). U-CTX-II showed a strong correlation to KOOS-4, with decreasing U-CTX-II with improvement in KOOS-4 (r=-.28, P=.0002), while S-COMP and U-CTX-I did not correlate to KOOS-4 (P>.097).
Conclusions: A weight loss over 16 weeks in obese knee osteoarthritis patients causes a reduction in S-COMP concentration directly associated with the magnitude of weight loss. Changes were also seen in U-CTX-II and U-CTX-I, but only the latter was correlated to the weight loss magnitude.
This study was supported by The Oak Foundation, The Velux Foundation, and The Cambridge Weight Plan.
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