Treating Joint Degeneration the Drug-Free Way

The Background -
Lameness resulting from joint degeneration or osteoarthritis (OA) is one of the most prevalent diseases affecting horses and the most common reason that vets are called out to competition horses. OA causes inflammation of the joint lining and progressive destruction of articular cartilage that covers the ends of the bones composing a joint. This destruction decreases both the natural shock-absorbing function and the range of motion of the joint, ultimately resulting in lameness in the affected animal.

Conventional treatments for joint disease include reduced or altered exercise regimes, bandaging, the use of anti-inflammatory agents, anti-arthritic drugs, artificial joint fluid and corticosteroids. For many years these treatments have helped to improve the condition of horses’ joints and subsequently helped maintain their overall soundness. Yet the fact is that all of them offer only limited efficacy; some are associated with side effects and the fact that some of them involve the administration of prohibited substances creates a headache for trainers.
New treatment
With these factors in mind, perhaps it’s not surprising that a completely new form of ‘drug-free’ treatment is attracting increasing interest from both the equine vets and trainers. While it’s still early days, its advocates believe that it may, over time, prove to offer a more effective and side-effect free way forward for the management and treatment of equine joint disease.
The new treatment, which is gaining an increasing foothold in the UK, US, Europe, Australia, South Africa and Saudi Arabia, is called an ‘autologous’ treatment because it effectively involves the horse healing itself.
A range of in-depth studies are underway to test the efficacy of autologous therapies and, while not yet conclusive, initial research results and anecdotal evidence are proving encouraging.
The causes
So, let’s examine how it works. Joint cartilage destruction is caused by a number of substances that increase when inflammation occurs in the joint.
Laboratory and clinical research has shown that one of the main substances responsible for cartilage destruction is interleukin 1 (IL-1). A multitude of research has also shown that antibodies produced against this cartilage-destructive substance can have a beneficial effect in arresting cartilage damage. A protein called IL-1RA has proved particularly helpful in this respect.
Treating the problem
The autologous treatment involves harnessing the regenerative and anti-inflammatory properties of the horse’s own blood cells, including IL-1RA to combat the IL-1, and encouraging damaged musco-skeletal tissues to heal. Effectively then the horse heals itself, a huge potential advantage for hard-pressed trainers trying to juggle horses’ treatment regimes around racing commitments.
The treatment involves a veterinary surgeon taking blood from the horse with a special syringe containing specially treated glass beads. The syringe is then incubated for 24 hours during which time white blood cells locate onto the beads and produce the regenerative and anti-inflammatory proteins.
After incubation, the syringe is placed into a special centrifuge to separate the serum from the blood clot and create a solution known as Autologous Conditioned Serum (ACS) – effectively a type of ‘anti-inflammatory soup’ with boosted levels of IL-1RA and other regenerative proteins. The ACS is then decanted into three to five vials for later intra-articular injection by the vet into the affected joints of the horse to reduce inflammation and initiate cartilage healing. Typically, three treatments are recommended for optimum clinical effect whilst the horse remains in training or is rested.
Results
A study published in 2005 and carried out at Colorado State University examined the efficacy of the ACS therapy compared to a control (placebo).
Sixteen horses were involved in the trial. Eight underwent the ACS therapy and the remaining horses were treated using saline solution. The horses were injected with the protein intra-articularly at weekly intervals for one month and then monitored for therapeutic success until day seventy of the trial. Factors measured included lameness, movement in the joint and a determination of the volume of synovial fluid.
The study demonstrated that compared to the control group the horses treated with the new therapy showed improvement in lameness and swelling.
Further examination histologically showed that there were also significant reductions in cartilage erosion with the ACS therapy compared to the control group.
The ACS process also encouraged the concentration of IL-1RA, the protein that promotes healing, to increase in the affected joints until day 70 showing that the benefit of the treatment is not short-lived.
Veterinary surgeon Dr. Thomas Weinberger, Müggenhausen, Germany, who led the study, commented: “The arthrosis study clearly demonstrates that the ACS Therapy is an efficient and safe alternative to common therapeutic interventions.”
The late Prix d’Amerique winner and world record trotter Victory Tilly is known to have undergone the treatment successfully.
The experience so far
So, what do equine vets make of this revolution? Consultant Equine Surgeon Cedric Chan BVSc CertES(Orth) DiplECVS MRCVS says the results he’s experienced so far have been encouraging but it’s too early for definitive conclusions.
A RCVS and European Recognised Specialist in Equine Surgery, who runs NW Equine Referrals, UK and France, based in England, Chan says: “I became interested in the therapy as a new physiological form of joint treatment for OA after attending a lecture by Professor Wayne McIlwraith and also using it at one of my referral centers in France, which was using it based on Orthogen’s (the company which first developed the treatment) experience.”
He has, in particular, used the treatment after arthroscopic surgery where OA had been demonstrated.
Neal Ashton, BVet Med Cert EP Cert ES (ST) MRCVS, shares Cedric Chan’s views: “The Autologous Conditioned Serum is now regularly considered at Oakham as an option for intra-articular joint disease in a range of joints. It’s proved particularly effective in treating horses which have been non-responsive to steroids.”
Ashton treats a high percentage of competition horses which are competed regularly and cites a key advantage of ACS as its flexibility when fitting in treatment around events. “Certainly trainers and riders seem to understand and are attracted by the concept of the horse healing itself,” he comments.
Andy Bathe MA, VetMB, DipECVS, DEO, MRCVS, Head of the Equine Sports Injuries Clinic at Rossdale & Partners (Newmarket, England) and another user, says: “I was the first user of the new therapy in the UK. Over the last eighteen months we’ve been pleased with the usefulness of this product in treating our practice population of racing Thoroughbreds, as well as on our referral population of a broader range of horses.
“We’ve found it helpful in the management of traumatic joint disease in racing Thoroughbreds, which have only been partially responsive to corticosteroids.
We’ve had some noticeable successes in helping high quality horses achieve the kind of success they deserve. We have also found beneficial effects in soft tissue injuries such as tendon and ligament injuries. It’s a very exciting technology and one which certainly adds to our armory when trying to treat injuries in these athletic horses.”
Lanark-based Clyde Vet Group recently treated the first horse in Scotland and Andrew McDiarmid BVM&S, Cert ES (Orth), MRCVS, head of the practice’s equine division, says: “While the use of this treatment is in its early stages, preliminary results are encouraging and it is definitely an exciting addition to our therapeutic range of treatments in the management of equine lameness. It represents new territory for equine vets and may herald the start of a completely new direction in treating joint disease.
At the moment, we, like other clinics, are primarily using it to treat cases that have not responded to conventional therapies.”
So, what’s the conclusion so far? “At its best, the therapy has proved extremely effective,” says Neal Ashton. “While it hasn’t worked in every case, I’ve treated racehorses which have gone on to win races and eventers which have got round Badminton and Burghley – something they would have struggled to do the year before.
ACS has a well-deserved place in our toolkit of treatments for joint disease.”
With more research indeed planned and in-depth studies underway, the development of autologous therapies could well be a key area to watch for 2008.

Howard Wilder (14 October 2008 - Issue 10) ​

Osteochondritis dissecans - the development, causes and treatments of OCD

By Deborah Spike-Pierce, DVM
​

One of the most common orthopedic problems encountered in young horses is osteochondritis dissecans (OCD).  This is of particular concern in the Thoroughbred industry, where horses are often bought and sold before maturation is complete and are expected to perform starting at a relatively young age.  There are many common sources of confusion surrounding this disease.  Deborah Spike-Pierce, DVM discusses research into the development, causes and treatment of OCD.

Development

In the most basic sense, OCD is caused by a disruption of the normal growth process of bone. It most commonly occurs in young fast growing animals such as large breed dogs, pigs and horses.  Normally, a cartilage framework in the growth plate at the end of a bone is slowly converted into bone as an animal grows.  If this ossification process is interrupted, the syndrome of OCD can result. There are three major stages of this disease, although the term OCD is commonly used to refer to all parts of the syndrome.  The first phase is osteochondrosis (OC), which is a disturbance of ossification of cartilage into bone resulting in excess retained cartilage.  If this retained cartilage results in inflammation of the joint, this stage is termed osteochondritis.  The inflammation may manifest itself clinically as joint distention or lameness.  Osteochondritis dissecans (OCD) is the stage where a portion of the retained cartilage loosens from the parent bone and forms a fragment.  The separated fragment may remain cartilage or it may ossify into bone.  It is the disturbance of this fragment that can cause the most severe clinical form of the disease by shedding debris into the joint, thus causing synovial effusion and lameness.  Not all horses that develop OC will go on to develop OCD.  In many cases, horses will have no clinical signs and areas of retained cartilage will go on to ossify normally as the horses grow with no long term consequences.

Many different parameters have been described as having an affect on the development of OCD. There is no apparent common denominator in OCD formation and the disease is multifactorial.  Nutritional imbalances, trauma, rate of growth, biomechanical influences as well as genetic predisposition have all been documented as potential causes.

Recent research on the relationship between nutrition and development of OCD have found multiple correlations.  It has been shown recently in the United States that the time of year can affect OCD rates due to spring and autumn peaks in the energy content of the grass.  In studies, horses fed diets with low copper, excess zinc, excess phosphorus and high digestable energy have all shown increased rates of OCD.  There has been an emphasis placed on copper intake, especially in pregnant mares, as copper has been shown to play an important role in the repair of osteochondrotic lesions.  Since mineral content of feed and forage vary throughout the world it is recommended to concentrate on a sound nutritional program since the nutritional contribution to OCD formation itself is multifactorial.

Certain sites in each joint are predisposed for OCD formation.  It is thought that a high mechanical load in areas of thickened cartilage where the blood supply is tenuous can lead to OCD due to traumatic causes.  Conformation may play a role in the distribution of the weight that the horse places on the developing bone.   It has been proposed that horses with a toe-out and upright conformation of their hindlimbs may have higher levels of hock OCDs.  This issue is intertwined with genetics as conformation is influenced by genetics.  Conformational variations can also induce more mechanical stress in particular areas and affect the ossification process via trauma.

Research investigating a possible link between genetics and OCD development is ongoing.  Studies in Standardbreds assessing the prevalence of hock OC have shown heritability rates ranging from 0.25 to 0.52.  These numbers appear significant, however certain warmblood studbooks will not allow stallions with hock OCD into their registry and after 20 years the incidence within the breed has not decreased.  This again supports the claim that OCD is a multifactoral disease.The most recent research on OCD development is at the molecular level.  The focus is on the development and maturation of cartilage, growth factors, collagen types and the expression and metabolism of these factors in bone development.

Osteochondritis dissecans can occur in many different joints but is most commonly identified in fetlocks, hocks and stifles.  Generally, the fetlocks are the first joints affected, followed by hocks, where OCD develops between 2-6 months of age.  OCD of the stifle and shoulder joints usually emerges later, often between 6-9 months of age.  In short, the larger the joint or the longer it takes to ossify, the later OCD develops.  These are the typical windows of susceptibility but since OCD may be traumatic as well as purely developmental in nature the disease may manifest itself at a later time.

Clinical Signs

In many cases, OC and OCD may be clinically silent, with no outward signs that a problem is occurring.  In other cases, there are outward manifestations of the disease.  Fetlock OCD may present as a foal or weanling with persistent distention of one or more fetlocks, with or without lameness.  Radiographs of the affected joints may confirm an OCD lesion.  However, traumatic chip fractures of P1 and sesamoid bone fractures present with similar clinical signs, so radiographs may show those lesions instead.

 
A foal or weanling with hock distention (bog) with or without lameness may also have OCD.  Hock OCD is often bilateral, even if distention is only present in one leg.  High quality radiographs are essential in this diagnosis, since small lesions may cause significant joint distention.

Stifle OCD can have a slightly different presentation, often found in a lame yearling with stifle distention.  Radiographs taken at the onset of the lameness and joint effusion may not show an OC or OCD lesion; it may require several weeks for the lesion to be evident radiographically.  However, even without radiographic evidence of a lesion at the onset of the problem, it is important to restrict exercise because the joint debris causing the effusion may result in significant damage to the articular cartilage with excessive exercise.

Diagnosis

A diagnosis of OC or OCD is most often made from radiographs.  OC lesions are characterized by a lucent area in the bone representing an area of retained cartilage.  OCD lesions often have a similar lucent area as well as the presence of a bony fragment.  However, some lesions are not able to be identified on radiographs and exploratory arthroscopy may be necessary to make the proper diagnosis.

Osteochondrosis lesions occur in specific anatomic sites in horses.  In a stifle, OCD lesions most commonly occur in the lateral trochlear ridge of the distal femur (Figure 1), the medial trochlear ridge of the distal femur and less commonly in the patella.  The most common area of OCD in the hock is the distal intermediate ridge of the tibia (Figure 2), followed by the distal lateral trochlear ridge of the talus and the medial malleolus of the distal tibia.  Fetlock OCD most commonly occurs in the proximal (Figure 3) and distal sagittal ridge of the distal cannon bones.

Since Thoroughbreds are sold at ages ranging from a few months old to adulthood, many variations of this syndrome are seen on survey radiographs.  In young horses, a lucency is often seen where the cartilage in this location has not fully ossified.  Many of these areas  will continue to ossify as the horse matures and not develop OCD.  However, some will go on to develop OCD. This is a grey area purchasers face when buying immature horses.

Treatment

Since there is not a preventive solution for OCD, horses with this disease often need to be treated.  This usually consists of either conservative medical management or arthroscopic surgery.  Conservative medical management has been shown to be successful in very young horses that still have the capacity to heal an OC or OCD lesion.  Regimes may include a modified exercise program, medication, and supportive therapy.  Exercise modification may involve reducing the intensity and amount of exercise (changing from large field to small paddock turnout, for example) or it may be as drastic as stall rest in severe clinical cases.  Medications focus on improving the health of the joint, decreasing inflammation, and augmenting the blood flow to the area of OC or OCD.  Supportive therapy can be as simple as bandaging an effused joint.

If a lesion is non-responsive to conservative management it may need surgical intervention. Surgical treatment is generally the treatment of choice in true OCD lesions that have a flap (versus the OC lesions that characterize the initial phase of this disease).  Surgery is recommended in these types of lesions even if the horse is not showing clinical signs.  It is likely that a true OCD lesion visible on radiographs will become a clinical problem in training and thus require down time for surgical treatment during the training or racing process.  Therefore, it is best removed before the joint is inflamed and further damage occurs.  Prognosis varies by joint but is generally favorable, except in the case of the shoulder joint.

In a study of Thoroughbreds with stifle OCD affecting the femoropatellar joint the affected horses’ overall racing performance was not significantly different than their unaffected siblings.  Fewer of these horses started races at two years old, but there was no difference at three years of age.  The size of a stifle lesion can be a concern when a horse is marketed; however no study has been able to link the size of the lesion with performance.  It is also important to note that the radiographic size of an OCD is not always consistent with the true size identified at surgery because a portion of the OCD is cartilaginous and therefore not identifiable radiographically. 
A study of hock OCD in Thoroughbreds and Standardbreds who underwent arthroscopic removal of the OCD lesion showed the overall racing performance was not different between affected horses and their siblings. The site of the lesion also had no impact in  performance.

There has not been a study published assessing racing performace in horses with fetlock OCD lesions.  However, studies involving multiple breeds show favorable results from surgery.  Ninety perfect of horses who had proximal sagittal ridge OCD lesions arthroscopically debrided returned to athletic activity.

Conclusion
Osteochondritis dissecans can be a confusing and concerning disease.  Although research into its causes is ongoing, there are many effective treatment options available.  Many lesions will heal without requiring surgical intervention and the prognosis for those requiring surgery is generally favorable as well.