The use of biomarkers to determine the severity of osteoarthritis in the tarsus of an older horse population

Abstract

Background: Osteoarthritis (OA) is a group of diseases of different causes that ultimately lead to synovitis, subchondral bone remodeling, and articular cartilage degeneration. OA commonly develops in the distal intertarsal (DIT) and tarsometatarsal (TMT) joints of performance horses. Currently, the most accurate method of identifying OA in these joints is a combination of thorough physical, lameness, and radiographic examinations. However, many horses may have pain attributed or localized to these joints with minimal radiographic changes present. A novel way to identify and classify the degree of OA is through the measurement of molecular biomarkers. Molecular biomarkers of OA reflect quantitative and dynamic variations associated with joint metabolism. Objectives: (1) define the direct and indirect biomarker concentrations in synovial fluid from the tibiotarsal, distal intertarsal, and tarsometatarsal joints in horses with varying degrees of tarsal OA, and (2) validate/refute that the biomarker concentrations in these joints increase with severity of OA in the distal joints as determined by a radiographs (all joints), MRI (PIT, DIT, TMT joints), arthroscopic evaluation/ gross pathology (TT joint), and (3) determine if biomarker concentrations in the TT synovial fluid (SF) can be used to evaluated OA severity in the DIT and TMT joints. Methods: A cohort study of 11 older horses (>8 years) with variable amounts of OA in the tarsal joints identified on radiographs were included. The TT joints were examined by arthroscopy/gross examination. The distal tarsal joints were examined by MRI. Biomarkers BAP, CPII, C2C, CTX II, CS846 were examined in the distal tarsal joints; additional biomarkers C1,2C, IL-1β, IL-6, IL-8, IL-10, and TNFα were examined in the TT joint. Various statistical analyses were used to determine association between imaging modalities and biomarkers to degrees of OA severity. Results: In the TT joint, C2C and IL-6 were the best biomarkers distinguishing OA severity. There was more pathology present in TT joints than could be seen on radiographs, suggesting that arthroscopic surgery is still the best method to evaluate TT joint OA. In the distal tarsal joints, radiographs were better at distinguishing OA and correlated to the corresponding MRIs, but underestimated the degree of SCB bone sclerosis, and number and size of osteophytes in many of the cases. MRI also provided information about cartilage damage and SCB hyperintensity. The severity of SCB sclerosis and presence of SCB hyperintensity on MRI was a good indicator for separating moderate/severe from mild OA. Of the biomarkers evaluated, the best at determining OA severity in the DIT joint were BAP, CPII, and C2C. These biomarkers also correlated to subchondral bone hyperintensity on MRI. In the TMT joint, CPII was the best biomarker to determine OA severity. No biomarker was identified in the SF in the TT joint capable of identifying OA in the distal tarsal joints. Conclusions: Biomarkers have the potential to be a valuable source of information about the OA disease process in the tarsal joints. SF from the joint of interest must be collected. Further research is needed with more horses. To the author’s knowledge, this is the first study examining biomarkers in an older horse population and hopes it provides a template for forthcoming research.