Using serum biomarkers to detect early change in joint tissues in horses

Using serum biomarkers to detect early change in joint tissues in horses

A breakthrough in early detection of osteoarthritis and prediction of fractures?
Jul 01, 2009

Figure 1: Post-mortem sample from leg opposite to that suffering catastrophic injury in a racehorse. Although there is intact articular cartilage, subchondral bone necrosis and sclerosis can be visualized. Courtesy of Norrdin RW, Kawcak CE, Capwell BA, McIlwraith CW. Subchondral bone failure in an equine model of overload arthrosis. Bone 1999:22;133-139.
Osteoarthritis is a common problem for the athletic horse and has been estimated to cause 60 percent of lameness cases in the athletic horse.

The osteoarthritic joint is characterized by damage to, and loss of, articular cartilage matrix components, along with reduced joint function. Early discussion on osteoarthritis (OA) in the horse extrapolated from human medicine, where it was considered that OA was a disease involving primary degradation in the articular cartilage and that all other events were secondary to this process. It is now clear that the sequence of events in equine OA is variable, but synovial membrane, fibrous joint capsule, articular cartilage, subchondral bone and intra-articular ligaments can all be involved in primary and/or secondary roles.

Most equine joint lesions probably are induced by acute trauma, repetitive load or overload. The inflammatory reaction in the synovial membrane and capsule, and any alteration in the dynamic equilibrium between biosynthesis and degradation of cartilage extracellular matrix (ECM) have been implicated in the pathogenesis of OA.

The inflammatory process results in increased levels of inflammatory mediators, and release of different macromolecules and their fragments into synovial fluid and serum follow the anabolic and catabolic processes in the articular cartilage.

Figure 2: Microdamage with (A) micro-crack formation and (B and C) osteocyte necrosis in samples from subchondral bone from a horse exercised on pasture (B) and on a treadmill (C). Courtesy of Dr. C.E. Kawcak.
Because the biochemical alterations caused by OA involve dynamic processes within all elements that constitute the joint, these mediators and products of tissue metabolism do not originate solely from the cartilage or the synovial membrane, but also from subchondral bone.

Clinical examination and radiographic imaging still are the most commonly used techniques for diagnosis of osteochondral disease, yet osteochondral damage seen during arthroscopic surgery is usually more severe than that seen on radiographs. It is the author's opinion that there usually is a good correlation between the severity of clinical signs (principally lameness and synovial effusion) and the amount of damage or disease found at arthroscopy of joints.

Figure 3: Principle of biomarker release from articular cartilage, bone and synovial membrane into synovial fluid, lymphatics, blood and urine.
However, in humans, although the most common complaint of a patient with OA is pain, only about half the patients with radiographic OA have symptoms (Hochberg et al., 1989). The reason(s) that these have or do not have pain is not always clear because only some causes of pain have been studied (Altman and Dean, 1989). There is no "diagnostic test" for OA in man (Altman, 1997), but focus on MRI and biomarkers for diagnosis has occurred in recent years.

Problem for racing industry

Of equal importance and certainly of more importance from an equine welfare perspective is the common occurrence of intra-articular fractures, many of which can be catastrophic. These fractures continue to be a serious problem for the horse racing industry, as both a significant cause of fatality and a common cause of days lost from training.

Not only is primary disease of the subchondral bone an important part of the osteoarthritic cascade (as mentioned previously), but it is also the initial event in pathologic fracture development at the level of the subchondral bone (most catastrophic fractures are intra-articular fractures in the metacarpophalangeal joint).

Work at the Orthopaedic Research Center at Colorado State University by Dr. Chris Kawcak demonstrated that microdamage in the subchondral bone can develop early when horses are subjected to athletic exercise on the treadmill.

In addition, post-mortem examination of racehorse joints at CSU (euthanized for catastrophic injury in another limb), has revealed a range of bone decrease, including microfractures, diffuse microdamage and primary osteocytic death. Figure 1 illustrates a sample from a horse euthanized because of catastrophic injury in the other limb. This incidental finding at post-mortem showed the presence of subchondral bone necrosis, with a peripheral area of sclerosis under intact cartilage in the distal palmar area of the metacarpus. Figure 2 shows microdamage and osteocyte necrosis that can occur early in association with exercise.

The ability to identify horses at increased risk of fracture before injury could be of considerable benefit, as it would allow early intervention aimed at preventing injury, e.g. by modification of a horse's training regimen.