Serum biomarkers in healthy, injured, and osteoarthritic knees: a critical review

Abstract

Introduction

Osteoarthritis (OA) can have deleterious effects on the joint. Many targeted strategies have been proposed to identify OA onset and progression prior to presentation of clinical symptoms and radiographic changes. Emerging research has focused on the utility of certain biochemical markers (biomarkers) as potential precursors of OA. Serum biomarkers have been widely studied across disease spectrums for their ability to classify the following characteristics: cartilage damage during early preradiographic stages, disease activity, severity or burden of disease, prognosis prediction, and response to certain treatment approaches. These classifications may be useful for understanding the evaluation and the qualification of biomarkers related to OA.

Objectives

The purpose of this critical review is to summarize and evaluate the existing serum biomarkers currently proposed for the identification and evaluation of osteoarthritis onset and progression in 3 populations: healthy-, anterior cruciate ligament reconstructed-, and osteoarthritic knees using the BIPED (burden of disease, investigative, prognostic, efficacy of intervention and diagnostic) classification.

Methods

Articles that reported on serum biomarkers in individuals with healthy, anterior cruciate ligament reconstructed and osteoarthritic knees were collected from peer-reviewed sources available on Medline (January 1, 2000 through March 31, 2020). Search terms included the following: serum AND biomarker AND knee AND osteoarthritis AND healthy AND (“anterior cruciate ligament” OR “anterior cruciate ligament reconstruction” OR “ACLR”). Articles were limited to studies in humans, written in English, and full text accessible. All serum biomarkers evaluated in the gathered articles were classified according to the BIPED classification.

Results

A total of 164 unique serum biomarkers were identified across healthy individuals, 18 reported on patients after knee injury (commonly anterior cruciate ligament reconstruction), 71 reported on patients with diagnosed osteoarthritis and 5 reported mixed populations. Biomarkers studied most frequently include serum COMP, interleukin-6, C2C, CPII, hyaluronic acid, tumor necrosis factor- alpha, c-reactive protein, MMP-3, high sensitivity-CRP, IL-8 and IL-1B, CS846, YKL-40, and C1,2C.

Conclusions

The results highlight large variations in how these biomarkers respond to different stimuli across multiple populations. The most frequently studied biomarkers were those categorized under the BIPED criteria as diagnostic, burden of disease and prognostic biomarkers. More robust and longitudinal research on serum biomarkers needs to be conducted in these 3 populations.