A “best-in-class” systemic biomarker predictor of clinically relevant knee osteoarthritis structural and pain progression

Abstract

We aimed to identify markers in blood (serum) to predict clinically relevant knee osteoarthritis (OA) progression defined as the combination of both joint structure and pain worsening over 48 months. A set of 15 serum proteomic markers corresponding to 13 total proteins reached an area under the receiver operating characteristic curve (AUC) of 73% for distinguishing progressors from nonprogressors in a cohort of 596 individuals with knee OA. Prediction based on these blood markers was far better than traditional prediction based on baseline structural OA and pain severity (59%) or the current “best-in-class” biomarker for predicting OA progression, urinary carboxyl-terminal cross-linked telopeptide of type II collagen (58%). The generalizability of the marker set was confirmed in a second cohort of 86 individuals that yielded an AUC of 70% for distinguishing joint structural progressors. Blood is a readily accessible biospecimen whose analysis for these biomarkers could facilitate identification of individuals for clinical trial enrollment and those most in need of treatment.

Bisdemethoxycurcumin, a curcumin, protects chondrocytes, and reduces cartilage inflammation via the NRF2/HO‐1/NLRP3 pathway

“…Age, gender, and obesity have been identified as major causative factors in addition to trauma 4 . Yet, the precise cause of OA remains a mystery 6,7 . Most of the existing medications are symptom‐based and while they may provide temporary relief, they may also be associated with certain side effects 8 .…”

An osteoarthritis pathophysiological continuum revealed by molecular biomarkers

“…We hypothesize that molecular entities predicting incident RKOA are similar to those predicting progression of RKOA because of a similar underlying molecular pathophysiology, thereby supporting the concept of a biological OA continuum. To test this hypothesis, we evaluated a serum proteomic biomarker panel that we showed predicted RKOA progression with initial discovery in the Foundation for National Institutes of Health (FNIH) cohort [a subset of individuals from the Osteoarthritis Initiative (OAI) with established RKOA] and with validation in the Biomarker Factory cohort ( 19 ). The current study was designed to evaluate the proteomic panel for its ability to predict incident RKOA in the Chingford 1000 Women study, a longitudinal cohort of middle-aged women with RKOA data available over 10 years.…”

From Bench to Bedside: Improving the Magic 8 Ball—Prognostication for Osteoarthritis

“…We recently made a substantial step forward in this regard for predicting progression of osteoarthritis (OA), which affects hundreds of millions of people and is a leading cause of disability worldwide [5]. Zhou and colleagues [6] very recently reported on a panel of 15 serum proteomic biomarkers that can distinguish knee OA progressors from nonprogressors. The specifics of their study are beyond both the scope of this column and my ability to explain them.…”

“…The research team followed patients for just three or four years, which might seem like a long time in orthopaedic clinical research, but in the context of a chronic disease like OA that can take decades to evolve, this is on the short side. Additionally, most patients already had moderate-to-severe OA at baseline, and the mean participant age was 65.8 years [6]. This is why the authors attempted to distinguish progressors from nonprogressors rather than, for example, OA developers versus nondevelopers.…”

“…The next step is further validation. Have Zhou and collaborators [6] actually discovered a crystal ball? This should happen concurrent with, or followed by, testing in patients with earlier stage OA or no OA at all.…”