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Alpha C-telopeptide of type I collagen is associated with subchondral bone turnover and predicts progression of joint space narrowing and osteophytes in osteoarthritis.

Publication ,  Journal Article
Huebner, JL; Bay-Jensen, AC; Huffman, KM; He, Y; Leeming, DJ; McDaniel, GE; Karsdal, MA; Kraus, VB
Published in: Arthritis Rheumatol
September 2014

OBJECTIVE: To evaluate joint tissue remodeling using the urinary collagen biomarkers urinary α-C-telopeptide of type I collagen (α-CTX) and urinary C-telopeptide of type II collagen (CTX-II) and to determine the association of these biomarkers with osteoarthritis (OA) severity, progression, and localized knee bone turnover. METHODS: Participants (n = 149) with symptomatic and radiographic knee OA underwent fixed-flexion knee radiography at baseline and 3 years, and late-phase bone scintigraphy of both knees at baseline, which were scored semiquantitatively for osteophyte and joint space narrowing (JSN) severity and uptake intensity, with scores summed across knees. Urinary concentrations of α-CTX and CTX-II were determined by enzyme-linked immunosorbent assay. Immunohistochemical analysis of human OA knees was performed to localize the joint tissue origin of the biomarker epitopes. RESULTS: Urinary α-CTX concentrations correlated strongly with the intensity of bone scintigraphic uptake and with JSN progression (risk ratio 13.2) and osteophyte progression (risk ratio 3). Urinary CTX-II concentrations were strongly associated with intensity of bone scintigraphic uptake, with JSN and osteophyte severity, and with OA progression based on osteophyte score. Urinary α-CTX localized primarily to high bone turnover areas in subchondral bone. CTX-II localized to the bone-cartilage interface, the tidemark, and damaged articular cartilage. CONCLUSION: Baseline urinary α-CTX, which was localized to high turnover areas of subchondral bone, was associated with dynamic bone turnover of knees, as signified by scintigraphy, and progression of both osteophytes and JSN. Urinary CTX-II correlated with JSN and osteophyte severity and progression of osteophytes. To our knowledge, this represents the first report of serologic markers reflecting subchondral bone turnover. These collagen markers may be useful for noninvasive detection and quantification of active subchondral bone turnover and joint remodeling in knee OA.

Duke Scholars

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Published In

Arthritis Rheumatol

DOI

EISSN

2326-5205

Publication Date

September 2014

Volume

66

Issue

9

Start / End Page

2440 / 2449

Location

United States

Related Subject Headings

  • Radiography
  • Osteoarthritis, Knee
  • Middle Aged
  • Male
  • Knee Joint
  • Humans
  • Female
  • Disease Progression
  • Collagen Type II
  • Collagen Type I
 

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Huebner, J. L., Bay-Jensen, A. C., Huffman, K. M., He, Y., Leeming, D. J., McDaniel, G. E., … Kraus, V. B. (2014). Alpha C-telopeptide of type I collagen is associated with subchondral bone turnover and predicts progression of joint space narrowing and osteophytes in osteoarthritis. Arthritis Rheumatol, 66(9), 2440–2449. https://doi.org/10.1002/art.38739
Huebner, Janet L., Anne C. Bay-Jensen, Kim M. Huffman, Yi He, Diana J. Leeming, Gary E. McDaniel, Morten A. Karsdal, and Virginia B. Kraus. “Alpha C-telopeptide of type I collagen is associated with subchondral bone turnover and predicts progression of joint space narrowing and osteophytes in osteoarthritis.Arthritis Rheumatol 66, no. 9 (September 2014): 2440–49. https://doi.org/10.1002/art.38739.
Huebner JL, Bay-Jensen AC, Huffman KM, He Y, Leeming DJ, McDaniel GE, et al. Alpha C-telopeptide of type I collagen is associated with subchondral bone turnover and predicts progression of joint space narrowing and osteophytes in osteoarthritis. Arthritis Rheumatol. 2014 Sep;66(9):2440–9.
Huebner, Janet L., et al. “Alpha C-telopeptide of type I collagen is associated with subchondral bone turnover and predicts progression of joint space narrowing and osteophytes in osteoarthritis.Arthritis Rheumatol, vol. 66, no. 9, Sept. 2014, pp. 2440–49. Pubmed, doi:10.1002/art.38739.
Huebner JL, Bay-Jensen AC, Huffman KM, He Y, Leeming DJ, McDaniel GE, Karsdal MA, Kraus VB. Alpha C-telopeptide of type I collagen is associated with subchondral bone turnover and predicts progression of joint space narrowing and osteophytes in osteoarthritis. Arthritis Rheumatol. 2014 Sep;66(9):2440–2449.
Journal cover image

Published In

Arthritis Rheumatol

DOI

EISSN

2326-5205

Publication Date

September 2014

Volume

66

Issue

9

Start / End Page

2440 / 2449

Location

United States

Related Subject Headings

  • Radiography
  • Osteoarthritis, Knee
  • Middle Aged
  • Male
  • Knee Joint
  • Humans
  • Female
  • Disease Progression
  • Collagen Type II
  • Collagen Type I