title: Association between biomarkers of tissue inflammation and progression of osteoarthritis: evidence from the Rotterdam study cohort.
abstract: BACKGROUND
  We aimed to investigate the prognostic value of two biomarkers of tissue inflammation, matrix metalloproteinase-dependent degradation of C-reactive protein (CRPM) and connective tissue type I collagen turnover (C1M), on the incidence and progression of radiographic osteoarthritis (OA) in the Rotterdam Study, a prospective cohort. Moreover, the independent effect of these biomarkers with respect to the established biomarkers of OA progression, like urinary type II collagen degradation (uCTX-II) and serum cartilage oligomeric protein (COMP), was evaluated.
  
  
  METHODS
  Serum levels of C1M, CRPM, COMP and CRP of 1335 participants aged >55 years were measured in fasting serum using ELISA. The commercial ELISA detecting CTX-II was used in urine. Radiographs at baseline and 5-year follow-up were scored for OA stage by Kellgren-Lawrence grade. The associations between progression and incidence of OA and the baseline biomarkers were examined using logistic regression and generalized estimating equations adjusted for age, sex, BMI, and possible other confounders.
  
  
  RESULTS
  The uCTX-II, COMP, and CRP concentrations were associated with the incidence and progression of OA. Moreover, OA progression was positively associated with CRPM (OR = 1.3, p = 0.01) and CRP (OR = 1.3, p = 0.01) levels with similar effect size as uCTX-II (OR = 1.3, p = 0.01) and COMP (OR = 1.2, p = 0.02). CRPM had prognostic value for progression of OA independent from the uCTX-II and COMP.
  
  
  CONCLUSIONS
  Our study confirmed the associations between uCTX-II and COMP concentrations and OA progression. Importantly, we showed for the first time that CRPM predicts the risk of OA progression independent of the established biomarkers uCTX-II and COMP.
authors.affiliation: Department of Internal Medicine, Erasmus University Medical Center, P.O. Box 2040, Rotterdam, 3000, CA, Netherlands.
authors.forename: Fatemeh
authors.initials: F
authors.lastname: Saberi Hosnijeh
authors.affiliation: Biomarkers and Research, Nordic Bioscience, Herlev, Denmark.
authors.forename: Anne Sofie
authors.initials: AS
authors.lastname: Siebuhr
authors.affiliation: Department of Internal Medicine, Erasmus University Medical Center, P.O. Box 2040, Rotterdam, 3000, CA, Netherlands.|Department of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors.forename: Andre G
authors.initials: AG
authors.lastname: Uitterlinden
authors.affiliation: Department of Radiology, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors.forename: Edwin H G
authors.initials: EH
authors.lastname: Oei
authors.affiliation: Department of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors.forename: Albert
authors.initials: A
authors.lastname: Hofman
authors.affiliation: Biomarkers and Research, Nordic Bioscience, Herlev, Denmark.
authors.forename: Morten A
authors.initials: MA
authors.lastname: Karsdal
authors.affiliation: Department of General Practice, Erasmus University Medical Center, Rotterdam, Netherlands.|Department of Orthopedics, Erasmus University Medical Center, Rotterdam, Netherlands.
authors.forename: Sita M
authors.initials: SM
authors.lastname: Bierma-Zeinstra
authors.affiliation: Biomarkers and Research, Nordic Bioscience, Herlev, Denmark.
authors.forename: Anne C
authors.initials: AC
authors.lastname: Bay-Jensen
authors.affiliation: Department of Internal Medicine, Erasmus University Medical Center, P.O. Box 2040, Rotterdam, 3000, CA, Netherlands. j.vanmeurs@erasmusmc.nl.
authors.forename: Joyce B J
authors.initials: JB
authors.lastname: van Meurs
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood*; D002097:C-Reactive Protein / Q000378:metabolism; D064236:Cartilage Oligomeric Matrix Protein / Q000097:blood; D015331:Cohort Studies; D024043:Collagen Type II / Q000097:blood; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000276:immunology / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010003:Osteoarthritis / Q000097:blood / Q000276:immunology / Q000473:pathology*; D010446:Peptide Fragments / Q000097:blood; D011379:Prognosis
chemical_list: D015415:Biomarkers; D002097:C-Reactive Protein; D064236:Cartilage Oligomeric Matrix Protein; D024043:Collagen Type II; D010446:Peptide Fragments; C000590554:C-terminal cross-linking telopeptide of type II collagen, human; C577553:TSP5 protein, human
keywords: Biomarker; CRP; Inflammation; Osteoarthritis; Prospective cohort