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

Abstract

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.

Association Between Biochemical Markers of Bone Turnover and Bone Changes on Imaging: Data From the Osteoarthritis Initiative

“…Our analyses were performed both with and without the inclusion of covariates, including age, sex, BMI, and K/L grade. It has been demonstrated that these demographic features and K/L grade may affect bone biochemical markers levels . Moreover, they were often independently associated with the imaging markers in our study.…”

Osteoarthritis Year in Review 2016: biomarkers (biochemical markers)

“…commercially available biomarkers were associated with age: sHA (rho ¼ 0.19), PIIANP (rho ¼ 0.27) and C1,2C (rho ¼ 0.20). Likewise gender differences were seen for uCTX-II, MMP-3, uCol2-1 NO 2 and sHA 45 . Cartilage damage and concentrations of sCOMP, sCTX-II, sMMP-3, sPIIINP, and sHA were determined in 79 patients who underwent knee arthroscopy or total knee replacement in a study by Jiao and colleagues 47 .…”

“…During the past year, OARSI has published a set of recommendations for the use of soluble biomarkers in clinical trials. The OARSI-endorsed publications summarize the key steps necessary for the qualification of a biomarker as a drug development tool and the various contexts for which OA biomarkers may be used 45,46 . In an effort to qualify more biomarkers as drug development tools, the Foundation for the National Institutes of Health/Osteoarthritis Initiative (FNIH/OAI) biomarkers consortium ef released the results of their soluble (urinary, abbreviated with a prefix u and serum, abbreviated with a prefix s) biomarker analysis 45,46 .…”

“…The OARSI-endorsed publications summarize the key steps necessary for the qualification of a biomarker as a drug development tool and the various contexts for which OA biomarkers may be used 45,46 . In an effort to qualify more biomarkers as drug development tools, the Foundation for the National Institutes of Health/Osteoarthritis Initiative (FNIH/OAI) biomarkers consortium ef released the results of their soluble (urinary, abbreviated with a prefix u and serum, abbreviated with a prefix s) biomarker analysis 45,46 . Among the important findings, the FNIH/OAI investigators found that time integrated concentrations, over a 24-month period, of urinary Ctelopeptide of type II collagen (uCTX-II), serum hyaluronan (sHA) and serum N-terminal telopeptide of type I collagen (sNTX-I) were associated with subject cases that had both progressive pain and radiographic progression of knee OA over a 4-year period (area under the curve (AUC) 0.63).…”

“…However, there were only a limited number of novel biomarkers; most were previously identified molecules such as matrix metalloproteinases (MMPs), interleukins, adipokines and joint related serum biomarkers MMP-degraded C-reactive protein (CRPM), MMP degraded type III collagen (C3M), cartilage oligomeric matrix protein (COMP), HA, N-terminal propeptide of collagen IIA (PIIANP), Col2-3/4 Cterminal cleavage product of types I and II collagen, uCTX-II, matrix metalloproteinase-3 (MMP-3) and urinary nitrated type II collagen degradation fragment (uCol2-1 NO 2 ) 45,46 . The first analytical data came from the OAI biomarker initiative where 18 biomarkers believed to be associated with OA were tested in 129 blood or urine samples from OA patients 45 . The data showed that three OA is a heterogeneous disease with a variety of pathophysiologic drivers leading to multiple phenotypes, many of which may overlap in patients.…”