Mechanically stimulated biomarkers signal cartilage changes over 5 years consistent with disease progression in medial knee osteoarthritis patients

Abstract

Using serum biomarkers to assess osteoarthritis (OA) disease state and risks of progression remain challenging. This study tested the hypothesis that changes to serum biomarkers in response to a mechanical stimulus in patients with medial knee OA signal cartilage thickness changes 5 years later. Specifically, serum concentrations of a collagen degradation marker (C1,2C) and a chondroitin sulfate synthesis marker (CS846) were measured 0.5 and 5.5 hours after a 30-min walk in 16 patients. Regional cartilage thickness changes measured from magnetic resonance images obtained at study entry and at 5-year follow-up were tested for correlations with baseline biomarker changes after mechanical stimulus, and for differences between groups stratified based on whether biomarker levels increased or decreased. Results showed that an increase in the degradation biomarker C1,2C correlated with cartilage thinning of the lateral tibia (R = -0.63, p = 0.009), whereas an increase in the synthesis marker CS846 correlated with cartilage thickening of the lateral femur (R = 0.76, p = 0.001). Changes in C1,2C and CS846 were correlated (R = 0.28, p = 0.037). Subjects with increased C1,2C had greater (p = 0.05) medial tibial cartilage thinning than those with decreased C1,2C. In conclusion, the mechanical stimulus appeared to metabolically link the biomarker responses where biomarker increases signaled more active OA disease states. The findings of medial cartilage thinning for patients with increases in the degradation marker and correlation of cartilage thickening in the less involved lateral femur with increases in the synthetic marker were consistent with progression of medial compartment OA. Thus, the mechanical stimulus facilitated assessing OA disease states using serum biomarkers. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:891-897, 2018.

Osteoarthritis year in review 2018: biomarkers (biochemical markers)

“…Individuals with lesser biomechanical loading on the ACLR limb at the 6-month follow-up exam, compared to the contralateral limb, demonstrated greater concentrations of plasma MMP-3 and IL-6, as well as serum type-II collagen turnover, indicating early interactions between mechanical joint loading and metabolic processes that may influence the future breakdown of cartilage and future KOA onset. In a small intervention study (n ¼ 16), changes to serum level of C1,2C and CS846 in response to a 30-min walk in patients with medial KOA was evaluated 52 . Regional cartilage thickness changes were measured from MRI obtained at study entry and at 5-year follow-up.…”

Modeling knee osteoarthritis pathophysiology using an integrated joint system (IJS): a systematic review of relationships among cartilage thickness, gait mechanics, and subchondral bone mineral density

“…The properties examined here were well motivated for a first systematic review in the framework of the relationship-based IJS model of OA pathophysiology and well developed in the literature. However, future reviews should consider other properties of the knee, such as inflammatory markers 57 , imaging-derived cartilage composition measures 58 , or markers of cartilage matrix turnover 59,60 , as these properties are also mechanosensitive and can be influenced by gait mechanics.…”

Concepts Important to Secondary Prevention of Posttraumatic Osteoarthritis

“…15 A follow-up study of patients with medial knee OA indicated that changes to CS846, a marker of cartilage matrix synthetic activity, predicted cartilage thickening in the less involved lateral compartment. 16 Similar elevations of CS846 were present in a subset of patients 2 years after ACLR. These data support the need to evaluate OA risk and rehabilitation outcomes by assessing the interplay among structure, biology, and mechanics after ACL injury.…”

“…14 Finally, serum biochemical biomarkers may play a role in the clinical assessment of OA disease states and OA risk. Previous researchers 15,16 showed that the change in serum biomarkers in response to a mechanical challenge provided insight into OA disease states. Specifically, changes to serum cartilage oligomeric matrix protein after a 30-minute walk predicted cartilage-thickness changes 5 years later in patients with knee OA.…”