title: Markers of bone formation and resorption identify subgroups of patients with clinical knee osteoarthritis who have reduced rates of cartilage loss.
abstract: OBJECTIVE
  To determine whether serum markers of bone formation and resorption, used individually or in combination, can be used to identify subgroups who lose cartilage volume at different rates over 2 years within a knee osteoarthritis (OA) population.
  
  
  METHODS
  Changes in cartilage volume over 2 years were measured in 117 subjects with knee OA using magnetic resonance imaging. We examined relationships between change in cartilage volume and baseline serum markers of bone formation [intact N-terminal propeptide of type I procollagen (PINP) and osteocalcin] and resorption [N-telopeptide of type I collagen (NTX-I), C-telopeptide of type I collagen (CTX-I), and C-telopeptide of type I collagen (ICTP).
  
  
  RESULTS
  The baseline markers of bone formation, PINP and osteocalcin (p = 0.02, p = 0.01, respectively), and the baseline markers of bone resorption, CTX-I and NTX-I (p = 0.02 for both), were significantly associated with reduced cartilage loss. There were no significant associations between baseline ratios of bone formation to resorption markers and cartilage loss. However, when subjects were divided into subgroups with high or low bone formation markers (based on levels of marker >or= mean or < mean for the population, respectively), in the subgroup with high PINP there was a significant association between increasing bone resorption markers CTX-I and NTX-I and reduced cartilage loss (p = 0.02, p = 0.001, respectively). Similarly, in the subgroup with high osteocalcin, there was a significant association between increasing CTX-I and NTX-I and reduced cartilage loss (p = 0.02, p = 0.003, respectively). In contrast, in subgroups with low bone formation markers, no significant associations were obtained between markers of bone resorption and cartilage loss.
  
  
  CONCLUSIONS
  Overall, the results suggest that higher bone remodeling (i.e., higher serum levels of bone formation and resorption) is associated with reduced cartilage loss. Considering markers of bone formation and resorption together, it is possible to identify subgroups within the OA population who have reduced rates of cartilage loss.
authors.affiliation: Department of Epidemiology and Preventive Medicine, Monash University, Central and Eastern Clinical School, Alfred Hospital, Melbourne, Victoria 3004, Australia.
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Berry
authors.forename: Rose A
authors.initials: RA
authors.lastname: Maciewicz
authors.forename: Flavia M
authors.initials: FM
authors.lastname: Cicuttini
authors.forename: Mark D
authors.initials: MD
authors.lastname: Jones
authors.forename: Caroline J
authors.initials: CJ
authors.lastname: Hellawell
authors.forename: Anita E
authors.initials: AE
authors.lastname: Wluka
mesh_terms: D015415:Biomarkers / Q000378:metabolism; D001862:Bone Resorption / Q000378:metabolism*; D002358:Cartilage, Articular / Q000378:metabolism / Q000473:pathology*; D024042:Collagen Type I / Q000097:blood; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D020370:Osteoarthritis, Knee / Q000378:metabolism / Q000473:pathology*; D015675:Osteocalcin / Q000097:blood; D010012:Osteogenesis / Q000502:physiology*; D010446:Peptide Fragments / Q000097:blood; D010455:Peptides / Q000097:blood; D011347:Procollagen / Q000097:blood; D011506:Proteins / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D024042:Collagen Type I; D010446:Peptide Fragments; D010455:Peptides; D011347:Procollagen; D011506:Proteins; C052929:collagen type I trimeric cross-linked peptide; C047202:procollagen Type I N-terminal peptide; D015675:Osteocalcin