Biomarkers aid early detection of joint disease, bone damage
Bone and articular cartilage turnover in horses occurs both in normal and abnormal states, in healthy and in damaged tissue.
In healthy cartilage, a slow constant turnover of the extracellular matrix occurs, and the rate of degradation does not exceed that of replacement. Bone formation and resorption regularly occur to repair skeletal microdamage and to maintain calcium homeostasis. During these processes, metabolites are released in a fairly steady state.
In diseased cartilage, however, various elements are liberated in excessive or unusual amounts, indicating a more severe situation. But there is a benefit:The ability to quantify degradation and formation products of bone and cartilage matrix elements can help in detecting disease or damage to equine joints, structural changes to articular cartilage, and potential bone damage prior to catastrophic injury.
The biomarkers of interest to clinicians are those of joint disease, osteoarthritis (OA) and bone disease or fracture that result in lameness and pain to horses and trauma to bone and joint tissue, those that are indicators of abnormal skeletal tissue turnover.
The potential for these markers, used along with radiographs and MRI, is to help equine practitioners detect/diagnose subtle or early damage to tissues, possibly prior to overt clinical signs or obvious lesions seen in x-rays.
During the last several years, researchers have developed assays to help clinicians use these biomarkers as a part of their diagnostic arsenal.
Bone is composed of mineral, and protein matrix, of which collagen Type I is the main organic constituent, making up about 80-90 percent. The remaining 10-15 percent is of non-collagenous proteins, including osteocalcin, glycoproteins and proteoglycans. The collagen matrix is made sturdy and durable by mineralization with hydroxyapatite crystals.
Within normal bone there is a balance of anabolic and catabolic processes of bone turnover. Bone formation is mediated via the osteoblasts, bone resorption via the osteoclasts, both resulting in release of various molecules. These molecular entities, or biomarkers, are indicative of bone turnover rate. And they can be measured in serum and urine as indicators of the physiological process.
Cartilage turnover is maintained via the chondrocytes that make up 0.15-0.2 percent of the total cartilage volume. The chondrocytes are protected by the extracellular matrix they produce. The primary constituents of the cartilage matrix are Type II collagen and the proteoglycan, aggrecan, which are synthesized and secreted from the chondrocyte. The dry mass of cartilage is about 60 percent collagen Type II, 20 percent proteoglycans. As water is drawn into the matrix, it produces the stiff elastic polymer resistant to impact loading.
With disease, the rate of cartilage degradation exceeds cartilage synthesis, producing a thinner, weaker and less resilient tissue.
Disease, i.e. osteoarthritis (OA) in horses, results from greater degradation and decreased repair of articular cartilage tissue, producing breakdown and erosion of the cartilage surface via extracellular proteineases.
However, early in the disease process, there is some synthesis. Several cartilage protein breakdown products are released into the synovial fluid, blood and urine, which can be measured as disease indicators.
Indirect and direct biomarkers
The disease process involves inflammation of the joints, pain, and loss of flexibility and movement, along with a disturbance of the homeostasis of turnover, producing an imbalance of formation and degradation products.
In OA, there is cartilage breakdown, inflammation of synovial membrane and production of cytokines and enzymes. As the disease proceeds, there is progressive loss of cartilage and subchondral bone change. These changes produce various products which can be measured.
Biomarkers are direct and indirect indicators of abnormal skeletal turnover.
According to Dr. C. Wayne McIlwraith, BVSc, PhD, FRCVS, Dipl. ACVS, Barbara Cox Anthony Chair, director of the Colorado State Equine Orthopedic Research Center (ORC), in equine disease, "the ideal biomarker/s should: