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
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
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
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
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:
- Detect joint damage at an earlier stage than conventional methods.
- Provide information on disease activity and progressive joint damage.
- Predict future illness and cause of disease.