Virginia B Kraus1, David E Hargrove2, David J Hunter3, Jordan B Renner4, Joanne M Jordan5. 1. Division of Rheumatology, Department of Medicine, Duke Molecular Physiology Institute, Duke University School of Medicine, Durham, North Carolina, USA. 2. LabCorp Clinical Trials, San Leandro, California, USA. 3. Rheumatology Department, Royal North Shore Hospital and Institute of Bone and Joint Research, Kolling Institute, University of Sydney, Sydney, New South Wales, Australia. 4. Department of Radiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA. 5. Department of Medicine, Thurston Arthritis Research Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
Abstract
OBJECTIVE: To establish reference intervals for osteoarthritis (OA)-related biomarkers used in the Foundation for the National Institutes of Health (FNIH) OA Biomarkers Consortium Project. METHODS: A total of 129 'multijoint controls' were selected from 2722 African-American and Caucasian men and women in the Johnston County Osteoarthritis Project. The majority (79%) of those eligible (with biospecimens and baseline data) also had one or more follow-up evaluations 5-15 years later. Multijoint controls were selected to be free of radiographic hand, hip, knee and lumbar spine osteoarthritis (OA), to have no knee or hip symptoms, and minimal hand and spine symptoms at all available time points. Eighteen biomarkers were evaluated in serum (s) and/or urine (u) by ELISA. Reference intervals and partitioning by gender and race were performed with EP Evaluator software. RESULTS: Controls were 64% women, 33% African-Americans, mean age 59 years and mean body mass index 29 kg/m2. Three biomarkers were associated with age: sHyaluronan (positively), sN-terminal propeptide of collagen IIA (positively) and sCol2-3/4 C-terminal cleavage product of types I and II collagen (negatively). Exploratory analyses suggested that separate reference intervals may be warranted on the basis of gender for uC-terminal cross-linked telopeptide of type II collagen (uCTXII), sMatrix metalloproteinase-3, uNitrated type II collagen degradation fragment (uCol2-1 NO2) and sHyaluronan, and on the basis of race for uCTXII, sCartilage oligomeric matrix protein, sC-terminal cross-linked telopeptide of type I collagen and uCol2-1 NO2. CONCLUSIONS: To our knowledge, this represents the best and most stringent control group ever assayed for OA-related biomarkers. These well-phenotyped controls, representing a similar age demographic to that of the OA Initiative-FNIH main study sample, provide a context for interpretation of OA subject biomarker data. The freely available data set also provides a reference for future human studies. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.
OBJECTIVE: To establish reference intervals for osteoarthritis (OA)-related biomarkers used in the Foundation for the National Institutes of Health (FNIH) OA Biomarkers Consortium Project. METHODS: A total of 129 'multijoint controls' were selected from 2722 African-American and Caucasian men and women in the Johnston County Osteoarthritis Project. The majority (79%) of those eligible (with biospecimens and baseline data) also had one or more follow-up evaluations 5-15 years later. Multijoint controls were selected to be free of radiographic hand, hip, knee and lumbar spine osteoarthritis (OA), to have no knee or hip symptoms, and minimal hand and spine symptoms at all available time points. Eighteen biomarkers were evaluated in serum (s) and/or urine (u) by ELISA. Reference intervals and partitioning by gender and race were performed with EP Evaluator software. RESULTS: Controls were 64% women, 33% African-Americans, mean age 59 years and mean body mass index 29 kg/m2. Three biomarkers were associated with age: sHyaluronan (positively), sN-terminal propeptide of collagen IIA (positively) and sCol2-3/4 C-terminal cleavage product of types I and II collagen (negatively). Exploratory analyses suggested that separate reference intervals may be warranted on the basis of gender for uC-terminal cross-linked telopeptide of type II collagen (uCTXII), sMatrix metalloproteinase-3, uNitrated type II collagen degradation fragment (uCol2-1 NO2) and sHyaluronan, and on the basis of race for uCTXII, sCartilage oligomeric matrix protein, sC-terminal cross-linked telopeptide of type I collagen and uCol2-1 NO2. CONCLUSIONS: To our knowledge, this represents the best and most stringent control group ever assayed for OA-related biomarkers. These well-phenotyped controls, representing a similar age demographic to that of the OA Initiative-FNIH main study sample, provide a context for interpretation of OA subject biomarker data. The freely available data set also provides a reference for future human studies. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.
Authors: G B Joseph; M C Nevitt; C E McCulloch; J Neumann; J A Lynch; U Heilmeier; N E Lane; T M Link Journal: Osteoarthritis Cartilage Date: 2018-05-23 Impact factor: 6.576
Authors: Leticia A Deveza; Virginia B Kraus; Jamie E Collins; Ali Guermazi; Frank W Roemer; Michael Bowes; Michael C Nevitt; Christoph Ladel; David J Hunter Journal: Arthritis Care Res (Hoboken) Date: 2017-07-10 Impact factor: 4.794
Authors: Marta Torres-Torrillas; Elena Damiá; José J Cerón; José M Carrillo; Pau Peláez; Laura Miguel; Ayla Del Romero; Mónica Rubio; Joaquín J Sopena Journal: Cartilage Date: 2021-12-03 Impact factor: 3.117
Authors: Hikmat N Daghestani; Joanne M Jordan; Jordan B Renner; Michael Doherty; A Gerry Wilson; Virginia B Kraus Journal: PLoS One Date: 2017-12-29 Impact factor: 3.240
Authors: Graham J Kemp; Fraser Birrell; Peter D Clegg; Daniel J Cuthbertson; Giuseppe De Vito; Jaap H van Dieën; Silvia Del Din; Richard Eastell; Patrick Garnero; Katarzyna Goljanek-Whysall; Matthias Hackl; Richard Hodgson; Malcolm J Jackson; Sue Lord; Claudia Mazzà; Anne McArdle; Eugene V McCloskey; Marco Narici; Mandy J Peffers; Stefano Schiaffino; John C Mathers Journal: Age Ageing Date: 2018-09-01 Impact factor: 10.668