Establishment of reference intervals for osteoarthritis-related soluble biomarkers: The FNIH/OARSI OA Biomarkers Consortium

Virginia B. Kraus, David E. Hargrove, David J. Hunter, Jordan B. Renner, Joanne M. Jordan

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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 OsteoarthritisProject. 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 massindex 29 kg/m2. Three biomarkers were associated with age: sHyaluronan ( positively), sN-terminal propeptide ofcollagen 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 crosslinked 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.

LanguageEnglish (US)
Pages179-185
Number of pages7
JournalAnnals of the Rheumatic Diseases
Volume76
Issue number1
DOIs
StatePublished - Jan 1 2017

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National Institutes of Health (U.S.)
Biomarkers
Osteoarthritis
Health
Collagen Type II
Spine Osteoarthritis
Collagen Type I
African Americans
Hip
Knee
Hand
Metalloproteases
Spine
Software
Enzyme-Linked Immunosorbent Assay
Demography
Urine
Degradation
Control Groups
Serum

ASJC Scopus subject areas

  • Rheumatology
  • Immunology and Allergy
  • Immunology
  • Biochemistry, Genetics and Molecular Biology(all)

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Establishment of reference intervals for osteoarthritis-related soluble biomarkers : The FNIH/OARSI OA Biomarkers Consortium. / Kraus, Virginia B.; Hargrove, David E.; Hunter, David J.; Renner, Jordan B.; Jordan, Joanne M.

In: Annals of the Rheumatic Diseases, Vol. 76, No. 1, 01.01.2017, p. 179-185.

Research output: Contribution to journalArticle

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