title: Diagnostic and prognostic value of bone biomarkers in progressive knee osteoarthritis: a 6-year follow-up study in middle-aged subjects.
abstract: OBJECTIVE
  To determine the value of bone markers in early-stage progressive knee osteoarthritis (OA), a population-based cohort of middle-aged subjects with chronic knee complaints was followed over 6 years (two consecutive two 3-year periods).
  
  
  METHODS
  Tibiofemoral (TF) and patellofemoral (PF) radiographs were graded in 128 subjects (mean age at baseline 45 ± 6.2 years) in 2002, 2005 and 2008. Bone formation was assessed by the serum concentration of procollagen type I amino-terminal propeptide (sPINP); bone resorption by the level of the C-terminal cross-linked telopeptides of type I collagen (sCTx-I); and bone mineralization by the values of osteocalcin (sOC) by electrochemiluminescence immunoassay. A novel marker of bone resorption, urinary osteocalcin midfragments (uMidOC), was assayed using enzyme linked immunosorbent assay (ELISA).
  
  
  RESULTS
  Several diagnostic associations were found between the bone markers (PINP, OC, MidOC) and progressive OA expressed by TF osteophytosis. The increasing output of MidOC demonstrated several-fold higher risk for progressive TF osteophytosis [odds ratio (OR) 5.32; 95% confidence interval (CI) 1.41-20.06, P = 0.014] than other bone markers. The values of PINP had prognostic value for subsequent more severely expressed knee OA progression [r(s) = 0.460, P = 0.005].
  
  
  CONCLUSIONS
  Bone metabolism is activated in early-stage knee OA. OA progression was preceded by the enhanced bone formation (by PINP) and accompanied by the activation of bone formation (by PINP), non-collagenous bone resorption (by MidOC), as well as by changes in mineralization (by OC). All three bone markers had diagnostic value, and one of them, PINP, had also a predictive value for knee OA progression, especially for progressive osteophytosis.
authors.affiliation: Clinic of Internal Medicine, University of Tartu, Tartu, Estonia. Jaanika.Kumm@kliinikum.ee
authors.forename: J
authors.initials: J
authors.lastname: Kumm
authors.forename: A
authors.initials: A
authors.lastname: Tamm
authors.forename: M
authors.initials: M
authors.lastname: Lintrop
authors.forename: A
authors.initials: A
authors.lastname: Tamm
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000378:metabolism; D001862:Bone Resorption / Q000378:metabolism; D024042:Collagen Type I / Q000097:blood*; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D005500:Follow-Up Studies; D006801:Humans; D008875:Middle Aged; D020370:Osteoarthritis, Knee / Q000378:metabolism*; D015675:Osteocalcin / Q000378:metabolism*; D010012:Osteogenesis / Q000502:physiology; D010446:Peptide Fragments / Q000097:blood*; D010455:Peptides / Q000097:blood*; D011347:Procollagen / Q000097:blood*
chemical_list: D015415:Biomarkers; D024042:Collagen Type I; D010446:Peptide Fragments; D010455:Peptides; D011347:Procollagen; C052929:collagen type I trimeric cross-linked peptide; C047202:procollagen Type I N-terminal peptide; D015675:Osteocalcin