Background Osteoarthritis (OA) is a slowly developing degenerative disease affecting the whole joint. Only few biomarkers (e.g. CTX-II and COMP) have been identified as predictors of OA progression. OA is heterogeneous in its aetiology and disease course and recent efforts are focussing on identifying subgroups of patients with distinct disease pathology. Inflammation is acknowledged to be important in disease pathology in a subset of OA population; however, the pathology of this subset is not well described and no radiographic longitudinal analysis of these patients has been presented.
Objectives We investigated the prognostic value of an MMP-derived CRP degradation fragments (CRPM) and connective tissue type I collagen turnover (C1M) on OA progression in a large population-based cohort. In addition, we compared the effects of these biomarkers to the established biomarkers for OA progression and investigated whether their prognostic value was independent.
Methods We investigated 1327 participants from the Rotterdam Study, who were aged >55 years. X-rays at baseline and 5 years follow-up were scored for radiographic OA stage by Kellgren-Lawrence (KL) grade. Progression of knee or hip OA was defined as an increase of at least 1 KL grade. At baseline there were 189 knee OA cases and 75 hip OA cases. After 5 years 122 participants had progression in the knee OA score, while 55 had progression in hip OA score. The following biomarkers were assessed in fasting serum; C1M, CRPM and COMP. The commercial ELISA detecting type II collagen degradation (CTX-II) was assessed in urine. Gender and age adjusted associations between biomarkers and OA progression were assessed by logistic regression analysis. Additionally, adjustments were made for BMI and baseline presence of OA (in case of OA progression). Furthermore, we performed a multivariate analysis with all 4 biomarkers.
Results Increased levels of C1M and CRPM were found to be significantly associated with a higher risk for progression of hip or knee OA (p=0.014 and 0.013 for C1M and CRPM, respectively). Adjustment for BMI and baseline presence of OA attenuated the effect of C1M. Interestingly, these potential confounders did not affect the association between CRPM and OA-progression (OR 2.7 [1.0-7.3], p=0.049). The magnitude of the association of CRPM was similar to the established CTX-II marker (OR 2.8 [1.1-6.2], p=0.012). A multivariate analysis including the biomarkers CRPM, COMP and CTX-II, and possible confounders, showed that all 3 biomarkers independently predicted OA-progression.
Conclusions We show for the first time that a marker of MMP-dependent inflammation is able to predict progression of OA independent of established biomarkers CTX-II and COMP. This indicates that inflammation is associated with fast disease progression in OA and that inflammation has pathological relevance in OA.
Disclosure of Interest A. S. Siebuhr Employee of: Nordic Bioscience, S. Bierma-Zeinstra: None declared, A. Uitterlinden: None declared, M. Karsdal Shareholder of: Nordic Bioscience, Employee of: Nordic Bioscience, A. Bay-Jensen Employee of: Nordic Bioscience, J. Van Meurs: None declared
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