title: Association Between Biochemical Markers of Bone Turnover and Bone Changes on Imaging: Data From the Osteoarthritis Initiative.
abstract: To determine the relationship between biochemical markers involved in bone turnover and bone features on imaging in knees with osteoarthritis (OA).
  
  
  
  We analyzed data from the Foundation for the National Institutes of Health OA Biomarkers Consortium within the Osteoarthritis Initiative (n = 600). Bone marrow lesions (BMLs), osteophytes, and subchondral bone area (mm2) and shape (position on 3-D vector) were assessed on magnetic resonance images, and bone trabecular integrity (BTI) was assessed on radiographs. Serum and urinary markers (serum C-terminal crosslinked telopeptide of type I collagen [CTX-I], serum crosslinked N-telopeptide of type I collagen [NTX-I], urinary NTX-I, urinary C-terminal crosslinked telopeptide of type II collagen [CTX-II], and urinary CTX-Iα and CTX-Iβ) were measured. The associations between biochemical and imaging markers at baseline and over 24 months were assessed using regression models adjusted for covariates.
  
  
  
  At baseline, most biochemical markers were associated with BMLs, with C statistics for the presence/absence of any BML ranging from 0.675 to 0.688. At baseline, urinary CTX-II was the marker most consistently associated with BMLs (with odds of having ≥5 subregions affected compared to no BML increasing by 1.92-fold [95% confidence interval (95% CI) 1.25, 2.96] per 1 SD of urinary CTX-II), large osteophytes (odds ratio 1.39 [95% CI 1.10, 1.77]), bone area and shape (highest partial R2= 0.032), and changes in bone shape over 24 months (partial R2range 0.008 to 0.024). Overall, biochemical markers were not predictive of changes in BMLs or osteophytes. Serum NTX-I was inversely associated with BTI of the vertical trabeculae (quadratic slope) in all analyses (highest partial R2= 0.028).
  
  
  
  We found multiple significant associations, albeit mostly weak ones. The role of systemic biochemical markers as predictors of individual bone anatomic features of single knees is limited based on our findings.
authors.affiliation: Royal North Shore Hospital and Institute of Bone and Joint Research, Kolling Institute, University of Sydney, Sydney, New South Wales, Australia.
authors.forename: Leticia A
authors.initials: LA
authors.lastname: Deveza
authors.affiliation: Duke University School of Medicine, Durham, North Carolina.
authors.forename: Virginia B
authors.initials: VB
authors.lastname: Kraus
authors.affiliation: Orthopaedic and Arthritis Center for Outcomes Research, Brigham and Women's Hospital, Boston, Massachusetts.
authors.forename: Jamie E
authors.initials: JE
authors.lastname: Collins
authors.affiliation: Boston University School of Medicine, Boston, Massachusetts.
authors.forename: Ali
authors.initials: A
authors.lastname: Guermazi
authors.affiliation: Boston University School of Medicine, Boston, Massachusetts, and University of Erlangen, Nuremberg, Erlangen, Germany.
authors.forename: Frank W
authors.initials: FW
authors.lastname: Roemer
authors.affiliation: Imorphics, Manchester, UK.
authors.forename: Michael
authors.initials: M
authors.lastname: Bowes
authors.affiliation: University of California, San Francisco.
authors.forename: Michael C
authors.initials: MC
authors.lastname: Nevitt
authors.affiliation: Merck KGaA, Darmstadt, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Ladel
authors.affiliation: Royal North Shore Hospital and Institute of Bone and Joint Research, Kolling Institute, University of Sydney, Sydney, New South Wales, Australia.
authors.forename: David J
authors.identifier: 0000-0003-3197-752X
authors.initials: DJ
authors.lastname: Hunter
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood / Q000652:urine; D016723:Bone Remodeling / Q000502:physiology*; D015331:Cohort Studies; D016208:Databases, Factual / Q000639:trends*; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging / Q000639:trends*; D008297:Male; D008875:Middle Aged; D020370:Osteoarthritis, Knee / Q000000981:diagnostic imaging* / Q000378:metabolism*; D011859:Radiography / Q000639:trends*
chemical_list: D015415:Biomarkers