NEWS
Pentosan polysulfate: The wonder from Down Under
Posted: Wednesday, January 18, 2012 10:24 AM
THERMOGRAPHY IMAGE OF INFLAMMED HOCK
Courtesy of Kenneth L. Marcella, D.V.M.
by Kenneth L. Marcella, D.V.M.
Pentosan polysulfate has been in use in Australia and various parts of Europe for more than 30 years. This multifaceted drug initially was used to help prevent blood clots and fat buildup in humans.
Researchers then discovered the anti-arthritic properties of sodium pentosan polysulfate, which was approved as an injectable treatment for osteoarthritis in dogs in Australia in 1986. New Zealand, the United Kingdom, Canada, and Ireland followed. Pentosan was soon approved for use as a joint treatment for humans throughout most of the European Economic Community, Scandinavia, South Africa, and Australia.
Although specific research investigating pentosan polysulfate’s possible benefits in the horse were not done at that time, veterinarians began using it as a treatment for equine osteoarthritis. Claims both for and against its efficacy have circulated for years.
Plenty of information suggests that pentosan polysulfate should work as expected to possibly reduce arthritis in the horse, but the veterinary research community has been relatively slow to do the testing required to prove such claims. However, recent studies have produced a more complete understanding of the workings of this anti-arthritic medication, which may have contributed to a new resurgence of interest in the use of pentosan polysulfate in sport horses in this country.
Pentosan is a polymer produced from beech wood. It can be administered orally, intramuscularly, intravenously or as a joint injection (intra-articularly). Adverse side effects are related primarily to dose. And because of pentosan polysulfate’s primary function as an anticlotting agent, it is not recommended for use in post-surgical cases, horses with prior bleeding problems, or in situations where trauma and possible bleeding could result.
Equine use
Because one of the primary areas in equine practice where arthritic treatment is routinely used is sport-horse medicine, and because these equine athletes are more at risk for exercise-associated trauma and possible bleeding, pentosan polysulfate use should be carefully considered, and attention should be paid to dosage and frequency. Veterinarians and trainers in Australia and Europe have routinely used pentosan polysulfate in racehorses with no documented increase in problems associated with exercise-induced pulmonary hemorrhage (EIPH) or other bleeding problems.
Statistics kept by Biopharm Australia Pty. Ltd., the company that produces and distributes pentosan polysulfate in that country as Cartrophen Equine Forte, have shown only 14 adverse drug reactions over a 14-year period ending in August 2007. Thirteen of these 14 horses were reports of injection-site reactions. Biopharm’s researchers concluded, “[These reports represent] a very low [estimated] incidence of adverse events on an individual-dose basis in the horse of less than 0.01%.”
This research also addressed the issue of possible bleeding problems, due to the drug’s anti-clotting properties. Normal clotting did not occur until 24 hours after administration of three milligrams per kilogram of body weight and 48 hours after administration of six milligrams per kilogram. The research advised that dosage and timing of administration are very important in athletic horses.
Helps arthritis
Pentosan polysulfate exerts an effect on arthritic joints in a number of significant ways. Although it has no analgesic or pain-reducing properties, its ability to influence the overall health of the equine joint has enabled it to be classified as a structure-modifying osteoarthritis drug. These compounds treat the cause of the arthritis process rather than simply alleviating the pain produced by that process.
The process of weight-bearing compression and slowly progressive osteoarthritis causes proteoglycans to be lost from the extracellular matrix, the supporting structure of the cartilage that makes up the joint-bearing surface. This weakens the matrix and contributes to a horse’s loss of athletic function. Pentosan polysulfate’s ability to stimulate the synthesis of proteoglycans is instrumental in halting the progression of arthritis.
Pentosan polysulfate also stimulates cells that help make up the joint capsule (synovial fibroblasts) to produce increased amounts of high-molecular-weight hyaluronic acid. This action serves to improve the viscosity and volume of the joint fluid, which lubricates and stabilizes the joint and helps limit further degradation of joint cartilage. Additionally, pentosan polysulfate inhibits and modulates inflammatory mediators, which have been implicated in the degradation of cartilage matrix.
The initial interest in pentosan polysulfate as a possible anti-arthritic drug stemmed from its ability to break down fat cells and fibrin, which is a central part of blood clots. Normal cartilage contains no blood supply, so it is dependent on the underlying bone’s blood vessels that bring needed metabolic nutrients.
The process of osteoarthritis erodes some joint surfaces, thickens others, and causes a general reduction in blood flow to the bone beneath the cartilage. Additionally, fats and fibrin are deposited in these stressed blood vessels, causing them to become clogged, further reducing blood flow, and adding to the destruction of joint cartilage. Pentosan polysulfate reduces blood clots, breaks down fat deposits, and actually encourages the regrowth of blood vessels. It is this property of pentosan polysulfate that results in better blood-derived nutritional support for bone and cartilage, improved metabolic activity in these tissues, and an eventual reduction in joint pain.
Research in the horse
All these effects of pentosan polysulfate have been demonstrated in species other than the horse. Although there has been ample reason to assume these beneficial actions would occur in sport horses as well, only recently have researchers provided some proof.
Cathy Fuller, B.V.Sc., Ph.D., and colleagues in the Department of Anatomy at the University of Bristol in Langford, England, were the first to demonstrate that intramuscular injections of pentosan polysulfate showed sufficient concentration of the drug in synovial (joint) fluid. This proved that injecting pentosan polysulfate into a horse’s muscle eventually got the drug into the joints. They reported, “The concentration was sufficient to elicit a potential therapeutic effect on synoviocyte metabolism, and possibly also to stimulate proteoglycan synthesis and reduce matrix metalloproteinase (one of the major cartilage degradation agents) activities in articular or joint cartilage.”
Just recently, David Frisbie, D.V.M., Ph.D., and members of the Orthopaedic Research Center at Colorado State University investigated pentosan polysulfate’s actions on 18 horses that underwent surgically induced osteoarthritis. In this study—one of the first to look at the clinical use of pentosan polysulfate in arthritis in horses—various parameters were used to determine the efficacy of pentosan polysulfate, including “blinded” lameness and range-of-motion examinations (research evaluators were not disclosed which horses had received the drug verses a placebo), analysis of blood and joint fluid, and serial radiographs.
Researchers in this study acknowledged that pentosan polysulfate produced trends that were not highly statistically significant but that showed more positive recordable differences between the treated and untreated groups at the cellular level than at the clinical level.
Frisbie’s group concluded, “This study has demonstrated that pentosan polysulfate has a beneficial therapeutic effect and, therefore, further study is indicated.” But it added, “Pentosan polysulfate may not be sufficiently potent to demonstrate a clinical effect at the current dose of three milligrams per kilogram.” This statement may be the reason many practitioners recommend a higher dose of pentosan polysulfate (up to six milligrams per kilogram). Again, dosage and timing of administration are very important in athletic horses.
Pentosan polysulfate is generally given in the muscle once weekly for four to five weeks and then monthly thereafter, though there are many variations on that protocol. Response is usually seen clinically after the first two doses.
A new product available in Australia combines pentosan polysulfate, glucosamine, and hyaluronic acid and is given intravenously every week for four weeks. This combination seeks to provide maximal help for the cells that make up the joint capsule, the joint fluid, and the articular cartilage, and the bone beneath (subchondral bone). This product is not yet available in the U.S., and pentosan polysulfate is not currently approved or being produced by a company in this country. However, it is available through compounding pharmacies as an off-label product, and its use and distribution should be controlled accordingly.
Perhaps it is its newness in this country or the constant search for a novel product that will allow equine athletes to perform at their best that has fueled the increased interest in pentosan polysulfate. Certainly recent research projects have given credibility to many of its anti-osteoarthritic claims and caused even skeptics to give it a closer second look, though clearly more clinically relevant research is needed.
Kenneth L. Marcella, D.V.M., is a practicing veterinarian in Canton, Georgia.
