New Approaches for Diagnosis of Equine Joint Disease and Estimation of Risk and Severity
C. Wayne McIlwraith BVSc, PhD, FRCVS, Diplomate ACVS
Professor and Director, Orthopaedic Research Center, Colorado State University
Early diagnosis of disease in the articular cartilage and subchondral bone is critical for prevention or retardation of the osteoarthritic process. It is equally important to recognize subchondral bone disease before it becomes a fracture or catastrophic injury. The joint is an organ and we need to be able to diagnosis disease in a number of tissues, including the articular cartilage, subchondral bone, synovial membrane, fibrous joint capsule, and the intra-articular ligaments.
Radiographs (x-rays) have been the gold standard of imaging for diagnoses of problems in the bone. They will diagnose fractures and also the end stage effects of osteoarthritis, such as spurs and loss of joint space. However, they are very limited in their ability to look at changes in the synovial membrane, fibrous joint capsule, ligaments, menisci and the subchondral bone. Injuries of all these areas may be early events in joint disease.
Synovitis and capsulitis is commonly the first event in the athlete resulting in pain and dysfunction, as well as the production of deleterious mediators that cause degeneration of the articular cartilage. In addition, we now have good evidence that all fractures into joints, whether they are small chip fragments or larger slab fractures and catastrophic fractures, start as subchondral disease. Subchondral microdamage has been shown in our laboratory to be a very early event associated with exercise. Most of the discussion here will revolve around methods of early diagnosis of disease. However, at the end of the talk we will discuss efforts being made to modulate the joint tissues early to be more resistant to developing problems and prevent injury.
The Need for Early Diagnosis
Early diagnosis is critical for two principal reasons: 1. Failure to treat any joint problem early and effectively will lead to osteoarthritis and 2. Failure to recognize early subchondral bone disease can lead to fractures, many of which are catastrophic. The spectrum of subchondral bone disease includes diffuse microdamage, focal microcracks, as well as bone sclerosis and bone necrosis (death of osteocytes, the cells responsible for making bone).
The following techniques can help early diagnosis. Obviously some are used more than others, but their uses and potential uses will be discussed.
The presence and degree of joint swelling or enlargement, as well as the degree of lameness are critical factors in assessing the amount of damage present in a joint. Most of the time the enlargement is due to excessive synovial fluid in the joint (synovial effusion), but in more chronic cases there can be fibrosis of the joint capsule. If the latter is present, there will also be decreased ability to flex that joint. There also will be pain with flexion. As a generalization, in cases of both OCD and traumatic injuries, the degree of synovial effusion and lameness correlates better than the changes seen on a radiograph.
This has been the standard technique to diagnose fractures and obvious bone disease. Computer and digital radiography systems have improved bone definition. In general, radiographic examination reflects pathologic change in the bone, and you can make specific diagnoses of fractures and OCD. Radiographs can insinuate major joint changes and it can also insinuate some soft tissue changes. The use of contrast radiography systems has been replaced by arthroscopy. While they can define some soft tissue changes, both ultrasonography and arthroscopy do it better. It is also to be noted that 50% loss of bone density needs to occur before it can be detected radiographically, so we do not get definition of early bone disease.
Nuclear Imaging (Bone Scanning or Centigraphy)
This is a very sensitive technique based on the injection of radioactive technetium attached to phosphorous. There are vascular soft tissue and bone phases, but most of the time we use the bone phase. Nuclear imaging is particularly useful for diagnosing early inflammation in tissues. The horse is injected with the technetium and 3 hours later, scanned with a gamma camera for areas of uptake (Figure 1).
The technique is very sensitive in leading to early areas of inflammation. However, it is non-specific and we need more specific imaging techniques to go along with the centigraphy. Nuclear imaging has contributed greatly to the early diagnosis of stress fractures in racehorses. Many of these stress fractures cannot be diagnosed with x-rays and, if they are undiagnosed can lead to a catastrophic fracture. When a catastrophic fracture is present in the pelvis, tibia, or humerus, as they commonly are, euthanasia is the only option. It is imperative, therefore, when have an athletic horse with a lameness that cannot be localized to the distal limb, that we use nuclear imaging to eliminate the presence of stress fractures higher up. These fractures usually heal with a period of rest and severe problems in the horse are thus prevented. Nuclear imaging is often unrewarding for more chronic problems.
Computer tomography is extremely useful for detecting early subchondral bone sclerosis and changes in subchondral density. An example is given in Figure 2, where it can be observed that a radiograph is equivocal in providing any change, but the CT can show quite a lot of change both in general bone density with exercise, as well as the specific problem. Figure 3 also shows changes in the distal metacarpus with exercise.
Figure 2A Figure 2B: Computer Tomography (CT)
CT has enabled us to advance our knowledge and ability to diagnosis early subchondral bone disease extremely well. The remaining problem, however, is one of practicality. At the moment, the CT we use at Colorado State University require anesthesia. Professor Elwyn Firth at Massey University has a portable unit that we were able to do CT's under sedation. The same company that makes the portable CT that is present at Massey University has developed a standing CT, which is under investigation at an equine clinic in France. When this becomes practical, CT offers a great potential tool for early diagnosis of bone change. With recognition of this early change, we can then go ahead and modulate training to prevent further injury.
Magnetic Resonance Imaging (MRI)
This is the gold standard of joints in human orthopedics. Figure 4 illustrates how it shows up change in a carpal joint. It is also of great value for diagnosing disease in the articular cartilage, ligaments, and menisci. We have recently installed and equine dedicated MRI at CSU and it is possible to image all the joints that we are interested in.
As with CT, routine use of MRI to detect early change and prevent injury requires a portable, practical unit. One such unit has been developed, but its field strength is such that it only can be used routinely for imaging the hoof. However, a machine with the field strength of capable of doing this and be used standing will ultimately be developed.
Ultrasonography has been used for many years for diagnosis and definition of tendon injury and ligamentous injury. It has been used more recently for early diagnosis for problems in the joint, and is capable of diagnosing defects in the articular cartilage, particularly OCD lesions, collateral ligament injuries, meniscal tears, as well as chronic proliferative synovitis in the fetlock joint. Until standing MRI is developed, ultrasound examination will probably serve as the gold standard for at least pre-arthroscopic determination of injuries in the joint capsule, meniscus, and cartilage. Sophisticated ultrasound machines are being developed that can diagnose cartilage injury.
Conventional Synovial Fluid Examination
Synovial fluid examination has been used for many years to diagnose infection in joints. The ability to diagnose infection is based on the marked reaction we obtain in the synovial membrane when infection is present. This reaction to inflammation is non-specific, but infection is the only disease process that gives us a certain level of white cell count or total protein in the synovial fluid. For many years, attempts have been made to diagnose the relative amount of cartilage or bone disease with synovial fluid examination, and the advent of biomarkers has helped this (see below). In the meantime, conventional synovial fluid examination remains as a very valuable technique to diagnose infection, but will not ascertain damage in other joints, and is therefore of limited value in preventing severe injury.
Synovial Fluid and Serum Biomarkers
The principal of synovial fluid and serum biomarkers is illustrated in Figure 5.
The principal is that because cartilage degradation involves disruption of the collagen framework, as well as loss of proteoglycan (breakdown and synthesis), products of Type II collagen and proteoglycans are liberated in increased concentrations into the synovial fluid and ultimately the serum. The uses of markers fall into three areas: 1. Improving knowledge and pathogenesis of equine joint disease, 2. Diagnosis of early disease, and 3. Monitoring a response to therapy (experimental and clinical). With regard to the diagnosis of early disease, biochemical and immunologic markers have been developed to provide knowledge on early change in both cartilage and bone. Most of the biomarkers are immunologic, involving the development of an anti-body that recognizes early breakdown change in the components that make up the cartilage and the bone. On the other hand, a biochemical marker measuring the total amount of glycosaminoglycan (GAG) gives us good ability to diagnose early osteoarthritic change in the articular cartilage.
So far, we have been able to develop a selection of markers that can diagnose early osteochondral disease in the joint and early changes with osteoarthritis. Our current research is addressing and ability to detect early changes in the subchondral bone, with the ultimate goal of being able to do a blood test and predict fracture, or at least predicts and increased chance of fracture in an athletic horse.
The markers utilize our ability to diagnose early synthetic changes (which are a common response to early injury), as well as degradation changes (Figure 6). Biomarkers also increase with exercise, and so it is important to differentiate changes with markers with exercise versus changes with disease in exercised horses. A recent project of ours has enabled us to do this.
New Techniques On The Horizon
Gene Chip Microarray
We have been working with an Australian company called Genetraks. Genetraks has developed a computer chip with 3,000 equine gene sequences on it. We have tested this gene chip technology with blood samples from horses developing osteoarthritis and have some significant gene expression changes. Ultimately, we feel that there will be a specific computer chip for different diseases, such as osteoarthritis or early subchondral bone damage, and will help us screen for the potential for injury.
This is a rather futuristic technique enabling computer modeling of all the forces on the tendons, bones, cartilage and ligaments of the joint. Modeling is a computer based mathematical representation of the skeleton, ligaments, and muscles used to calculate forces in muscles and joints. These forces would change with conformation or possibly with the way a horse normally goes. Ultimately we feel that once we have the legs of the horse completely modeled, that with the combination of CT, MRI, and visual examination, we can make predictions of early injury, as well as assessing the potential for a certain individual to injure themselves and possibly with shoeing changes, or conformation manipulation early in life, decrease the likelihood of this injury occurring.
Global Equine Research Alliance
This is a major project that has been done at Massey University with a principal hypothesis that early conditioning of equine limbs can lead to decreased injury when the horses go into athletic activity. The study has been done with New Zealand thoroughbreds, and is a collaboration between Professor Elwyn Firth and Dr. Chris Rogers at Massey University, Dr. Chris Kawcak and myself and Colorado State University, Professors Alan Goodship and Roger Smith at the University of London, and Professor Barneveld and Dr. Rene van Weeran at the University of Utrecht. The project started with 32 foals, and half the foals received a structured exercise program, beginning at 3 weeks of age. At 18 months, both groups came together and went into racing training. Some useful is being developed as far as the difference between the two groups and the modulation of their musculoskeletal tissues, as well as early diagnosis of injury, early disease in the tendons, ligaments, joints, and bones.