Arthritis: When Bones Collide
The old gray mare, she ain't what she used to be. She doesn't move as easily as she once did; she doesn't jump fences or wheel around the paddock with the same grace and fluidity she had in her youth. On cold and rainy days, she comes out of her stall feeling positively creaky. She doesn't care for having her feet held up for long periods of time by the farrier, or for working on hard ground.
What's up with the old gray mare? Well, in a word, osteoarthritis. Whether it was years of wear and tear that started the process, or a single, traumatic injury, she's now experiencing the painful after effects--when synovial fluid in her joints thins and fails to lubricate, the cartilage that provides a smooth articulating surface breaks down, and bone ends up grinding excruciatingly against bone. No wonder the old gray mare doesn't want to flex her joints the way she once did!
Osteoarthritis probably accounts for the end of more equine performance careers than any other single cause. And until recently, it was considered an irreversible process. New research, however, offers some hope, and there are now several treatments that can significantly improve joint lubrication, slow or halt the deterioration of the joint surfaces, and reduce pain and inflammation--giving horsemen valuable options for coping with this destructive condition.
A horse's joints are marvels of biological engineering, especially considering the extreme pressures brought to bear on the equine skeleton in motion. That the bones involved can glide frictionlessly over, under, around, and against each other is due to the ingenious interior structure of each joint.
In a normal, healthy joint, the ends of the bones are coated with a thin layer of friction-reducing articular cartilage. They are surrounded by a joint capsule with a tough outer layer (to connect the bones and protect the joint) and a permeable inner layer, or synovial membrane, which secretes synovial fluid and allows the passage of nutrients and other elements from the bloodstream. Synovial fluid, a slippery, viscous liquid that many researchers describe as being about the same consistency as egg whites, fills the joint capsule, nourishes the articular cartilage, and provides essential lubrication.
Synovial fluid is a nutrient-rich brew that contains proteins and enzymes, water, leukocytes, and the key ingredient sodium hyaluronate, which is responsible for the fluid's elastoviscous qualities. Sodium hyaluronate (formerly known as hyaluronic acid) is a negatively-charged sugar chain, or glycosaminoglycan (GAG), which arranges itself in complicated coils, adapting to the pressure changes in the joint capsule as the horse moves. It assures the unhindered passage of metabolites to and from tissues throughout the joint, and also serves as a stabilizer and shock absorber for the structures that are undergoing continual, changing mechanical stresses.
Cartilage, the other main shock-absorbing component of a joint, is an efficient but flawed structure. Its structural framework is a web of collagen fibers, with cells called chondrocytes scattered along the matrix. Chondrocytes produce giant proteoglycan molecules that resemble bottle brushes and bind the GAGs; the GAGs in turn extract and loosely hold large amounts of positively charged water molecules. When cartilage is damaged, there is a decrease in the number of GAGs; therefore, the cartilage holds less water.
Among the talents of cartilage: it conforms to the bone surfaces for a tight fit between weight-bearing bones; it spreads pressure evenly over a broad area; and it "manages" the water in its matrix, squeezing it out when the joint is under pressure, and drawing it back in when the joint is "unweighted." This in and out movement of the fluid transports nutrients throughout the cartilage. Cartilage also, in a way, acts like a sponge, conforming to loading demands by changing its shape and size, and regaining its original shape when the pressure is off. This "squeeze film lubrication" is the most important part of cartilage on cartilage lubrication. This cartilage lubrication is much like hydroplaning--there is a thin coat of water between surfaces acting to decrease the coefficient of friction.
But here's the downside: cartilage is one of the body's most primitive structures. It has no blood or nerve supply of its own, so cartilage has little or no ability to heal or repair itself. Only in rare cases when the cartilage is torn directly off the bone can healing take place (because the resulting space allows capillaries to break through and patch up the holes with fibrocartilage). Even then, the repair work is substandard and won't stand up to repeated stresses. As a result, although cartilage performs admirably under normal conditions, it only takes a 5-10% overload of work stresses to begin the process of cartilage breakdown.
A Vicious Cycle
The effects of the wear and tear of hard work, uneven or unyielding footing, and poor conformation might trigger the deterioration of cartilage, which is where osteoarthritis begins. Although the horse notices no pain at this stage and continues to work with no observable lameness, inside his joints, havoc is ensuing.
As soon as cartilage cells begin to erode, the cells of the synovial membrane respond by cleaning up the debris--a classic inflammatory response. Although the debris-eating cells are simply doing their job, the action of breaking down and removing the foreign bodies from the area changes the chemical makeup of the fluid in the joint, introducing excess fluids and a greater concentration of destructive enzymes and prostaglandins into the closed space and destroying the lubricating sodium hyaluronate. The synovial fluid begins to lose viscosity, becoming less like egg whites and more like water.
Deprived of its protective cushioning and lubrication, the cartilage breaks down further. More enzymes are released to clean up the second round of debris, and that creates even more inflammation. Now swollen and sore, the joint experiences increased friction as the synovial fluid gets thinner, the synovial capsule thickens, and the vicious cycle accelerates.
Eventually, chondrocytes, suffering from a compromised nutrient supply, can't keep up with repairs, and the cartilage develops pits, holes, and fissures, opening the bone ends to direct trauma. The bone responds with a defense that only causes further destruction--it lays down new bone to strengthen the surface (a process called sclerosis) and extend its margins (bone spurs and osteophytes). In its final stages, if left unchecked, arthritis causes the fusing of equine joints.
When Is It Arthritis?
Once cartilage damage is noticeable, most researchers categorize the condition of the horse's joints as officially arthritic. But in the early stages, cartilage damage might be very subtle (and because cartilage has no nerve endings and does not register pain, the horse might appear sound). The two earliest stages of degenerative joint disease (DJD) are synovitis (inflammation of the synovial membrane) and capsulitis (inflammation of the joint capsule). Both are common signs of overworked joints and possible conformational weaknesses.
Other precursors of arthritis include injuries of the ligaments within a joint; pre-existing articular cartilage damage (sometimes originating with developmental orthopedic disease episodes in the horse's youth, causing abnormal cell growth and thickened, brittle cartilage); and osteochondral fractures (also known as bone chips, and especially common in the fetlock and knee joints). Any of these can start the cycle of inflammation in a joint and instigate the breakdown of cartilage.
Most owners and trainers are well-acquainted with the signs of arthritic changes in their horses. Although the degree of lameness might be mild (and is sometimes only seen at faster gaits), the swelling of the joint capsule, heat, pain response on palpation and flexion, and the decreased range of motion are telltale.
While osteoarthritis can target practically any joint, it is particularly common in "high-motion joints"--including the fetlocks, upper (antebrachiocarpal) joint of the knee, and the hock joint, according to Roy Pool, DVM, PhD, a leading researcher in equine joint pathology from the University of California, Davis. In a seminar on joint function presented at the 1995 American Association of Equine Practitioners Convention, Pool noted, "High-motion joints and low-motion joints (such as the pastern joint) have different patterns of movement and are subjected to different forces during athletic performance. Therefore, they undergo different patterns of degenerative joint disease."
In the same vein, the occupation of the horse will greatly influence the pattern of wear and tear, with certain occupations leading to a higher percentage of arthritis in one area of the body versus another area.
Suspicions of arthritic damage can be confirmed by taking a sample of synovial fluid. Laboratory analysis can detect decreased levels of sodium hyaluronate, increased protein levels, and decreased viscosity of the joint fluid. Even color can be an indicator: normal synovial fluid is a very pale straw color, while the fluid from a joint coping with arthritis is often dark or blood-tinged.
A particle analysis can establish counts of circulating white blood cells (the type and number of which can indicate infection), synovial lining cells, cartilage cells, and bone cells--the more cells, and the more cartilage cells in particular, the worse the prognosis. Possible bone fractures also can be indicated by minute particles of bone floating in the fluid.
C. Wayne McIlwraith, BVSc, PhD, Diplomate ACVS, of Colorado State University, and one of North America's leading experts on equine osteoarthritis, has reported that joint fluid analysis should be a routine part of evaluating arthritic conditions.
Radiographic exams are useful as well, but X rays won't detect early signs of degenerative joint disease or infectious arthritis. They can, however, point out fractures and bone fragments, and can help provide a piece of the puzzle.
Arthroscopy (in which a slender optical instrument is inserted into the joint cavity) gives the most definitive diagnosis of arthritis, as your veterinarian can actually see the extent of the damage. Most veterinarians, however, do not routinely use arthroscopy as a diagnostic because it is an invasive procedure requiring anesthesia.
Cartilage, Heal Thyself
At least two researchers are making promising inroads into the realm of cartilage repair, offering hope that arthritic changes may someday be reversed. At Cornell University, Alan Nixon, BVSc, MS, Diplomate ACVS, is working on a series of studies that involve growing chondrocytes in culture, stimulating them with specific growth factors (small proteins involved in cell repair and growth and hormone stimulation), and grafting them back into arthritic joints.
Just growing cartilage cells in vitro is a bit of a feat. Nixon's team has managed it by harvesting bone marrow-derived stem cells from the same animal to be treated later for arthritis.
"Bone marrow stem cells can adapt to becoming cartilage cells, if you treat them right and talk to them carefully," reports Nixon with a smile.
Over several weeks, with the influence of specific growth factors (themselves the product of futuristic recombinant DNA cloning, resulting in yeast cultures that produce the proteins in large quantities), the cells develop into creditable chondrocytes, which later are carefully placed, with the aid of an arthroscope, at the sites of cartilage damage in a joint.
The ingenious factor in Nixon's experiments is a biological "glue" called fibrin, which literally acts like epoxy to help attach new chondrocytes to the original cartilage surface and keep them there long enough to take hold and grow. Fibrin has two components, fibrinogen and thrombin, which function in the body to form blood clots. Mixed on injection into the joint at the time of a cartilage graft, the fibrinogen (to which growth factors have been added) and thrombin combine to form a rubbery, bloodless clot which slow-releases growth factors over a period of weeks. The grafted chondrocytes result in a much-improved cartilage surface, with tissue that is close to normal.
"It looks like this is one of the best results we've had so far," says Nixon. "(The cartilage) is so much better attached, and it tends to stick around longer, which is crucial."
But while the process is extremely promising, it's not likely to evolve into a simple procedure that can be performed in the average barn.
"It's quite involved," says Nixon, "and you need to be very good with an arthroscope. Furthermore, the horse must be placed under general anesthetic to collect the bone marrow stem cells from the sternum or hip. I think its use by practitioners is still a few years away."
Meanwhile, McIlwraith's team at Colorado State University is investigating the use of a "micropick" technique borrowed from human orthopedic surgeon Richard Steadman, MD. In an effort to encourage cartilage repair and regrowth, the micropick is used to make tiny holes in the subchondral bone underneath the damaged cartilage in equine joints--a significant advance over previous methods of debriding cartilage, which usually injured the subchondral bone in the process. Maintaining the bone integrity means that cartilage has a better blood supply and nutrient source for regrowth, and initial results are encouraging.
McIlwraith's team is now investigating the addition of growth factors to encourage even better healing of cartilage.
Both of these studies might provide valuable techniques for the future. But what can be done right now to treat an arthritic horse?
Methods of treating osteoarthritis have come a long way in recent years. Nonetheless, stall rest still seems to be one of the best general treatments. The use of hydrotherapy (cold water and/or ice packs) can help reduce inflammation and swelling in the acute phase of the injury. The reality, however, is that many horses' careers don't permit extended layoff time. Consequently, the treatment most often chosen until relatively recently has been the injection of corticosteroids into the joints.
Nothing beats corticosteroids when it comes to quick relief. They hold inflammation-causing interleukins and enzymes at bay, decrease pain, and reduce the swelling of the synovial membrane, while improving nutrient and waste exchange to the joint. But there's a steep price to pay with these benefits. Corticosteroids put a wrench in the process of normal healing and can mask lameness symptoms, encouraging horse and owner to vigorously use a joint that is by no means healed. As a result, they have often been implicated as encouraging the eventual deterioration of the joint, rather than helping it.
On top of this, studies have indicated that corticosteroids might have a deleterious effect on chondrocytes and GAGs in the articular cartilage. How much of an effect this has on cartilage function is still unclear, but most veterinarians recommend caution when it comes to repeated doses of corticosteroids, and they emphasize sufficient stall rest even when the joint seems improved.
Dimethyl sulfoxide (DMSO), applied topically, is often used in combination with corticosteroids to help reduce swelling and inflammation in joints. A free-radical "scavenger," DMSO has become a standard in most horsemen's medical kits as it has both a powerful anti-inflammatory action and a unique ability to penetrate swiftly through tissues, carrying other drugs throughout the site up to three times faster than they would travel otherwise.
Non-steroidal anti-inflammatories (NSAIDs) such as phenylbutazone, naproxen, and flunixin meglumine (Banamine) have been used for pain relief in arthritic conditions for decades. Administered systemically (orally or by injection), they prevent prostaglandin production and block pain receptors, and also have an anti-inflammatory effect. Less damaging, and less potent, than corticosteroids, they provide only temporary pain relief, rather than actual healing; in addition, the long-term use of some NSAIDs has been implicated in gastrointestinal ulcers.
Joint lavage, a pricey technique performed under local or general anesthesia, is an option to consider with certain types of joint damage (particularly where bone chips are suspected). Flushing fluid through the joint often helps rinse out many of the irritating particles that aggravate cartilage and stimulate an over-eager immune response; lavage is sometimes done in conjunction with arthroscopic surgery to remove bone fragments.
The arrival of injectable sodium hyaluro-nate, in 1970, was a breakthrough in the treatment of equine arthritis, although original results didn't live up to researchers' expectations. It was soon discovered that it was most useful when administered early in the cycle of damage, rather than as a last-ditch effort for a severely damaged joint. Used appropriately, sodium hyaluronate (which goes under several different brand names, and is often sourced from rooster combs or human umbilical cords) can provide significant relief and actually promote the production of natural sodium hyaluro-nate within the joint.
Until recently, sodium hyaluro-nate has been administered intra-articularly (injected into the joint), but studies now have indicated that intravenous injection is also effective (and considerably easier to use), finding its way to the injured joint and going to work to increase the viscosity of the synovial fluid and inhibit damaging enzymes. Most remarkably, it encourages the body to manufacture more of its own sodium hyaluronate. The action by which it does this is unclear, but joints injected with exogenous hyaluronate do show a significant improvement in sodium hyaluronate concentrations long after the injectible has dissipated. This, combined with the anti-inflammatory action of the drug, makes sodium hyaluronate a powerful tool. It can also be used as a maintenance medication when no acute inflammatory symptoms exist but chronically poor synovial fluid is produced.
Because the pharmacology of hyaluronate is so complex, it will probably never be inexpensive, but it does pay to shop around. Several studies have indicated that the higher the molecular weight and concentration of the sodium hyaluronate, the better the results (both in terms of duration of soundness and percent improvement in flexion and movement).
Another powerful tool in combatting osteoarthritis is polysulfated glycosaminoglycan (PSGAG), commonly known by the trade name Adequan. Of all the drugs currently available, PSGAG (which first arrived on the North American market in 1984) is probably the most powerful; it combines all the healing properties of sodium hyaluronate with a unique chondroprotective quality (meaning it protects the cartilage from further deterioration, and might even help lay down new cartilage by binding to the existing cartilage structure).
PSGAG has been shown in studies to inhibit more than a dozen lysosomal enzymes, as well as interleukins and superoxide radicals both in the joint capsule and the cartilage matrix itself. It also encourages the joint capsule to synthesize sodium hyaluronate and promote the cartilage to lay down new collagen and proteoglycans. So in effect, it can actually reverse the symptoms and damage of arthritis. Studies have demonstrated that PSGAG is even more effective than sodium hyaluronate in reversing lameness and inflammation, and maintaining that improvement over time; in a large clinical trial, veterinarians classified approximately 91% of arthritic horses' responses to PSGAG treatment as good or excellent.
Of course, nothing this good comes without a price. Manufactured from bovine tracheal cartilage, PSGAG undergoes a lengthy extraction and purification process that pushes its price upwards of $100 a dose (and several doses are generally needed to show response; some horses remain on a maintenance program for life). It can be administered either intra-articularly (which of course opens the horse's joint to the possibility of infection) or intra-muscularly, where it shows the same talent for "finding" the trouble spots as does hyaluronate. (If used intra-articularly, most veterinarians recommend a concurrent course of antibiotics.)
There also are several products on the market which purport to be oral forms of glycosaminoglycans, usually in the form of chondroitin sulfate. There are opposing opinions regarding efficacy of these oral forms in the veterinary community. In a study by Gary White, DVM, et al., published in the Journal of Equine Veterinary Science in 1994, twelve horses with similar arthritic lesions demonstrated no benefit from after more than a month of feeding oral GAGs, either from a chondroprotective or anti-inflammatory point of view.
Deciding which treatment to use on your own old gray mare is dependent in large part on how advanced the arthritic changes are, and how much work you expect of her. Sodium hyaluronate, while less expensive than PSGAG, is most effective in cases caught at the synovitis/capsulitis stage; PSGAG might be the first line of defense when the damage is more severe. If the horse is only mildly affected, you might decide instead to just maintain her with judicious use of anti-inflammatories like bute, and reduce her workload. If the damage is extremely severe, as in a "dry" joint (one in which the cartilage erosion is very deep and the synovial fluid is of very poor quality), the sad truth is there are no miracles, and nothing can reverse the degradation.
Nixon points out, pragmatically, that "traumatic joint disease is going to be with us forever. It goes with the activities we ask of these horses. Things wear out, and if you ask the maximum of them, they sometimes wear out faster."
The same, of course, can be said of us all...but at least veterinary science is now providing some terrific tools with which to help us in dealing with osteoarthritic conditions.
About the Author
Karen Briggs is the author of six books, including the recently updated Understanding Equine Nutrition as well as Understanding The Pony, both published by Eclipse Press. She's written a few thousand articles on subjects ranging from guttural pouch infections to how to compost your manure. She is also a Canadian certified riding coach, an equine nutritionist, and works in media relations for the harness racing industry. She lives with her band of off-the-track Thoroughbreds on a farm near Guelph, Ontario, and dabbles in eventing.
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