{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T17:05:07Z","timestamp":1790269507085,"version":"4.1.0"},"reference-count":50,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2014,8,26]],"date-time":"2014-08-26T00:00:00Z","timestamp":1409011200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"NIH","award":["AR050245"],"award-info":[{"award-number":["AR050245"]}]},{"name":"NIH","award":["AR48769"],"award-info":[{"award-number":["AR48769"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatology"],"published-print":{"date-parts":[[2014,9]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>To evaluate joint tissue remodeling using the urinary collagen biomarkers urinary \u03b1\u2010C\u2010telopeptide of type I collagen (\u03b1\u2010CTX) and urinary C\u2010telopeptide of type II collagen (CTX\u2010II) and to determine the association of these biomarkers with osteoarthritis (OA) severity, progression, and localized knee bone turnover.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Participants (n = 149) with symptomatic and radiographic knee OA underwent fixed\u2010flexion knee radiography at baseline and 3 years, and late\u2010phase 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 \u03b1\u2010CTX and CTX\u2010II were determined by enzyme\u2010linked immunosorbent assay. Immunohistochemical analysis of human OA knees was performed to localize the joint tissue origin of the biomarker epitopes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Urinary \u03b1\u2010CTX 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\u2010II concentrations were strongly associated with intensity of bone scintigraphic uptake, with JSN and osteophyte severity, and with OA progression based on osteophyte score. Urinary \u03b1\u2010CTX localized primarily to high bone turnover areas in subchondral bone. CTX\u2010II localized to the bone\u2013cartilage interface, the tidemark, and damaged articular cartilage.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Baseline urinary \u03b1\u2010CTX, 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\u2010II 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.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.38739","type":"journal-article","created":{"date-parts":[[2014,6,6]],"date-time":"2014-06-06T10:37:59Z","timestamp":1402051079000},"page":"2440-2449","source":"Crossref","is-referenced-by-count":51,"title":["Alpha C\u2010Telopeptide of Type I Collagen Is Associated With Subchondral Bone Turnover and Predicts Progression of Joint Space Narrowing and Osteophytes in Osteoarthritis"],"prefix":"10.1002","volume":"66","author":[{"given":"Janet L.","family":"Huebner","sequence":"first","affiliation":[{"name":"Duke University School of Medicine Durham North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne C.","family":"Bay\u2010Jensen","sequence":"additional","affiliation":[{"name":"Nordic Bioscience Herlev 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