Pentosan Polysulfate to Control Clinical Signs of Osteoarthritis
A recent FDA study on the use of pentosan for osteoarthritis (OA) was conducted at 12 practices throughout the USA. Scott McClure, DVM, PhD, DACVS, DACVSMR of Midwest Equine Surgery and Sports Medicine in Iowa, presented the current summation on this medication at the 2022 AAEP Convention.
Pentosan, derived from beechwood hemicellulose, was originally used as an antithrombotic agent for blood clots in people. Its effect is only 1/6-1/10 that of heparin, and even weaker in horses. In the joint, pentosan is said to preserve proteoglycans, stimulate hyaluronic acid synthesis and act as a fibrinolytic agent. In vitro studies demonstrate protection against free radicals and increases in insulin-like growth factors.
The multicenter FDA study for the approval process for pentosan was a negatively controlled, randomized, blinded field efficacy study. Included horses had to be in good health and at least two years old with the presence of moderately advanced OA in one limb confirmed with radiologic evidence. Lameness presented as Grades 2-4. The horses had not had surgery, NSAIDs or other treatment.
The protocol for the FDA study called for a 38-day study of 219 horses, aged 3-32 years. Pentosan was administered at 3 mg/kg IM once a week for four weeks. The control horses received saline. A previous study (McIlwraith et al.) at this dose demonstrated a significant decrease in articular cartilage fibrillation and an overall positive outcome in the histologic appearance of cartilage. There was also a positive outcome in lameness and in joint flexion. There were decreased cartilage degradation products in the synovial fluid.
In the multicenter study, there was 60% success in horses treated with pentosan compared to 36% in horses “treated” with saline only. The pentosan-treated horses also experienced significant decreases in globulin, neutrophils, white blood cell count and total protein compared to the saline group. This indicates a significant decrease in whole-body inflammation. Fewer than 10% of horses experienced an adverse reaction at the injection site, such as edema, heat, pain and redness.
In summary, pentosan at 3 mg/kg once a week for four weeks significantly decreased lameness and was well tolerated. McClure reported that 60% success is notable because of the advanced nature of OA in horses enrolled in the study. There might be value in using this medication earlier in the disease process. In fact, in other countries, pentosan is being used prophylactically.
Equine Blood Flow Restriction Safety Validation
Rehabilitation of limb injuries is critical to athletic longevity in horses. Sherry Johnson, DVM, DACVIM of Equine Sports Medicine and Rehabilitation discussed a promising protocol used by the Department of Defense to rehabilitate veterans with serious limb injuries: blood flow restriction. She also discussed how this protocol was validated for safety in horses. In addition, Johnson reported that blood flow restriction is now being used in human pro-athletes to strengthen muscles, as well as in geriatric patients, especially those with neurologic dysfunction.
Johnson explained human application like this: A pressure cuff on a proximal part of a limb is inflated to the point of reducing arterial blood flow by 80% and venous blood flow by 100%. While the cuff is in place, the patient performs 30 reps of a particular exercise. Vascular occlusion for this period of time “wrings” out remaining oxygen from the muscles so that fast-twitch muscle fibers—important components of muscle strength output—are recruited. The person performs the reps at a very low load, i.e. 20-30% of optimal effort.
Johnson described the objectives for equine application:
- Improve muscle size and strength without applying damaging loads
- Avoid loss of muscle mass that comes with rest
- Increase growth hormone up to 290 times, and lactate accumulation
The benefits of BFR in horses are many. Muscle margins rounded, blood vessels remained engorged for hours after a BFR session, and muscles improved in hyperechogenicity on ultrasound. BFR improved bone healing in addition to muscle healing. It also improved superficial digital flexor tendinopathy when used for three weeks with no walking.
The safety study included four horses over a 56-day study period with 40 unilateral BFR sessions. The contralateral limb was used as the control. Horses were evaluated with objective gait analysis on days 0, 28, and 56. All clinicians were blinded. The limb occlusion pressure (LOP) was determined by doppler and then ratcheted back to deliver 80% LOP vaso-occlusion at a walk on a treadmill. A protection sleeve protected the skin where the cuff was applied, and Elastikon secured the cuff in place. Dynamic inflation was delivered by a hose to the cuff that attached to the surcingle.
The results indicated that there was no evidence of venous or arterial thrombosis. There was also no evidence of dermatitis, swelling, thickening or sensitivity with palpation. The carpal joints did not experience any effusion, and the BFR did not induce clinical lameness or complications. Johnson stressed that limb occlusion pressures must be individualized to each horse as there is an inherent physiologic variation between horses and between forelimbs.