Gary W. White

The Efficacy of Orally Administered Sulfated Glycosaminoglycan in Chemically Induced Equine Synovitis and Degenerative Joint Disease

Summary The efficacy of oral supplements containing sulfated glycosaminoglycans (GAGs) for the prevention/treatment of equine joint disease was evaluated in a randomized, blinded, controlled study using an adjuvant induced model of synovitis and degenerative joint disease (DJD) in horses. Twelve horses free of clinical and radiographic evidence of synovitis or DJD were stratified by age and sex and randomly assigned to two groups of six horses. After a 10-day acclimation period, synovitis was induced in the right radiocarpal joint by intra-articular injection of Frcunds Complete Adjuvant (CFA). One group of horses received a commercially available supplement containing sulfated GAGs at the dosage and treatment regimen recommended by the manufacturer. Treatment began 10 days prior tomodel induction and continued until 26 days after model induction. The second group Parameters of efficacy included lameness score, stride length, carpal circumference, maximum carpal flexion, and synovial fluid protein. These were measured prior to model induction and at 5, 12, 19, and 26 clays after model induction. Radiographs of the right carpus were taken prior to and 26 days after model induction. There was no evidence of benefit from the treatment with the sulfated GAG supplement in any parameter measured when compared to untreated controls. We conclude that commercially available orally administered sulfated GAGs at the dosage and treatment regimen recommended by the manufacturer had no anti-inflammatory or chondroprotective activity compared to untreated controls in the CFA induced equine carpitis model.

Efficacy of Intramuscular Chondroitin Sulfate and Compounded Acetyl-d-Glucosamine in a Positive Controlled Study of Equine Carpitis☆

Abstract Summary Thirty healthy lameness-free horses were subjected to the Complete Freunds Adjuvant (CFA) (Sigma, St Louis, Mo) carpitis model, which was allowed to develop for 5 days. The horses were then stratified by model-induced deficit in lameness score, carpal flexion, stride length, and carpal circumference, and they were randomly assigned to 3 groups of 10 horses. The horses were treated with one of 3 treatments beginning on day 5: Group A (positive control) received PSGAG (Adequan, Luitpold Pharmaceuticals, Inc, Shirley, NY); Group B received a compounded solution of acetyl-d-glucosamine (Red Cross Drug, Blanchard, Okla); and Group C received a solution of chondroitin monosulfate (Chondroprotec, Neogen Corp, Lexington, Ky). All horses received the treatments by intramuscular injection every 4 days for 4 weeks and all doses were 500 mg/5 mL. On days 12, 19, 26, and 33, the primary outcome measures were taken for lameness score, carpal flexion, stride length, and carpal circumference. The study was blinded because the clinician evaluating the outcome measures was unaware of the treatment group assignments. The group means for percent recovery of model-induced deficits in these parameters was subjected to statistical analysis. PSGAG was significantly ( P

Evaluation of the efficacy of various preparations of sodium hyaluronate in an induced equine carpitis model

Summary A study was performed to evaluate the efficacy of three formulations of sodium hyaluronate in an induced carpitis model. Sixteen healthy mature Quarter Horse type horses free of lameness and carpal disease had carpitis induced by injection of Complete Freunds Adjuvant in the left radial carpal joint. Five days after model induction the horses were assigned to four groups of four horses each and treated with either placebo, intravenous sodium hyaluronate, intraarticular low molecular weight sodium hyaluronate or intraarticular high molecular weight sodium hyaluronate. Lameness variables and synovial fluid variables were measured prior to model induction, just prior to treatment and across 16 weeks post treatment. Radiographs were taken prior to model induction and at six and 16 weeks post treatment. An attempt to evaluate exercise tolerance was also made. Gross and histopathology were performed on one randomly selected animal from each treatment group at week 16. Results confirmed efficacy of all formulations of sodium hyaluronate in the relief of lameness as compared to placebo. Model induction led to a dramatic decrease in synovial fluid hyaluronate concentration and mean molecular weight. All treatments restored the hyaluronate concentrations to premodel normal levels and all treatments led to an increase in model induced deficits in mean molecular weight of synovial fluid hyaluronate; only the high molecular weight intraarticular preparation restored the mean molecular weight to premodel normal levels. Statistically significant findings in the lameness data along with trends seen in synovial fluid parameters support improved efficacy and longer duration of efficacy for the high molecular weight sodium hyaluronate preparation. Statistical weaknesses due to small group sizes and design flaws in the study prevented definitive conclusions.

The efficacy of systemically administered anti-arthritic drugs in an induced equine carpitis model

Summary The efficacy of two systemically administered drugs for the treatment of equine joint injuries was assessed in a randomized blinded trial using the chemically induced equine carpitis model previously used to determine the dose and efficacy of both products. After a 10-day acclimation period, carpitis was induced by intracarpal injection of Complete Freunds Adjuvant (CFA) in twenty mature horses free of clinical and radiographic evidence of synovitis or DJD. Five days after model induction, the horses were stratified based on lameness evaluation and randomly assigned to 2 groups of 10 horses each. Parameters evaluated included lameness score, maximum range of carpal flexion, carpal circumference, stride length, and synovial fluid protein. These parameters were measured prior to model induction, 5 days after model induction (immediately prior to initial treatment) and once weekly for 6 weeks. Radiographs of the carpus were taken prior to model induction and 6 weeks. after treatment began. Treatment began 5 days after model induction. One group of 10 horses received 40 mg sodium hyaluronate by intravenous injection weekly for 3 weeks and the other group of 10 horses received intramuscular injections of 500 mg PSGAG every 4 days for 7 treatments. Both treatment groups showed significant improvement from pretreatment baseline values (based upon percent recovery to normal pre-model induction values) for lameness score, stride length and maximum carpal flexion (p Both intravenous sodium hyaluronate and intramuscular PSGAG induced significant improvement in clinical lameness parameters; intramuscular PSGAG yielded consistently better results in this experimental model.

The current status of the clinical use of polysulphated glycosaminoglycan in the USA

It is now approximately 10 years since PSGAG (Adequan IA | was approved for introduction into the U.S. market for the intraarticular (IA) treatment of equine degenerative joint disease (DJD).I Prior use had been limited to an illicitly imported PSGAG formulation (Arteparon | for human use; neither dose nor dosage regimen had been established. The recommended and US Food and Drug Administration (FDA) sanctioned intraarticular dose of 250 mg weekly for five weeks had been approved as the minimal optimal dose. 1 This was based on a dose titration study in induced DJD disease model with support from clinical studies .2 The dose was nevertheless questioned in view of prior use of lower doses of illicit PSGAG, of cost, of the need for 5 treatments, and of determination of dose in an experimental syndrome. The 250 mg IA dose is now generally accepted. Supporting pharmacokinetic data for such an IA dose has not however been derived in the horse, z Evidence in man and rabbits suggests

Can we attenuate the effect of joint injuries on young racehorses by administration of intramuscular polysulfated glycosaminoglycan

Non-septic joint injuries and inflammation remain a major problem in equine athletes and this seems especially true of young racehorses. Many recent advances in medicine and surgery have provided equine practitioners with better ways to medically manage these syndromes. Arthroscopic surgery has reduced soft tissue trauma and recovery times after intraarticular surgery. Better understanding of equine joint physiology and pathobiology has led to newe medications (such as sodium hyaluronate and polysulfated glycosaminoglycan) and provided a new appreciation for the application of older medications (such as nonsteroidal antiinflammatory agents and corticosteroids). Hopefully such pathobiologic and pharmacologic understandings will lead to a decrease in joint injuries and diseases in equine athletes; this does not