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"The Efficacy of Various Sodium Hyaluronate Preparations with Respect to Molecular Weight and Route of Administration in an Induced Equine Carpitis Model"
Presented By:
Gary W. White DVM, Sallisaw Equine Clinic, Sallisaw, Oklahoma, USA
Based on "Evaluation of the Efficacy of Various Preparations of Sodium Hyaluronate in an
Induced Equine Carpitis Model" as published in the Journal of Equine Vet Science,
volume 19, number 5, May 1999
Introduction: The effectiveness of sodium hyaluronate (SH) for the
treatment of equine joint injuries has been well established and accepted in equine practice. There
are several commercial preparations of SH available, and these vary in molecular weight, recommended
dose and route of administration. Confusion and controversy exist due to these differences. This
trial was an attempt to examine the effect of molecular weight and route of administration on
efficacy of SH in an established model of equine carpal synovitis and degenerative joint disease.
Materials and Methods: Sixteen mature horses were obtained from a local
supplier. The horses were determined to be healthy and free of lameness and carpal disease. A
synovitis was induced by aseptic injections of Complete Freund's Adjuvant in the left radial carpal
joint. The model was allowed to develop for 5 days. The horses were then stratified by severity of
lameness and randomly assigned to one of 4 treatment groups:
1. Placebo (PL)
2. Intravenous SH (HAIV) (40 mg/4 mL)
3. Intra-articular SH at a molecular weight of about 300,000 daltons (LWHA) (20 mg/2 mL)
4. Intra-articular SH at a molecular weight of about 3,000,000 daltons (HWHA) (20 mg/2 mL).
One treatment was administered on post model induction day 5. The following variables were measured
prior to model induction, just prior to treatment and at post treatment weeks 1, 2, 4, 6, 8, 12, and
16: lameness score (evaluated weekly post treatment), maximum carpal flexion, carpal circumference,
stride length, synovial fluid protein, synovial fluid hyaluronate concentration, and mean molecular
weight of synovial fluid hyaluronate (MMWHA). Horses that became free of lameness were subjected to
treadmill exercise to evaluate ability to tolerate exercise. The study was blinded; separate
investigators administered treatment and collected measurements.
Results: Only 4 horses became free of lameness during the trial and
these were stressed on the treadmill. Of these, 3 were from the HWHA group and one was from the LWHA
group. The LWHA horse was only able to tolerate exercise for 3 days. The 3 HWHA horses tolerated
exercise for an average of 4.5 days. The increased amount of exercise in the HWHA group might have
influenced the outcome of the clinical variables for this group, as stress from exercise could have
aggravated the induced joint disease.
Graphs 1-5 compare the mean lameness scores for the various groups. Mean lameness scores improved in
all 3 drug-treated groups compared to the PL group. Lameness score for the HAIV group was significantly
better than the PL group at post treatment week 3. For the LWHA group, the lameness score was
significantly better than the PL group at post treatment weeks 3,7,8,9, and 12. In the HWHA group,
lameness score was significantly better compared to the PL group at post treatment weeks 2-12. The
lameness scores for the LWHA group were significantly better than the HAIV group at post treatment
week 8 and the HWHA group was significantly better than the HAIV group at post treatment weeks 7-10
and 12. There were no significant differences in mean lameness scores between the HWHA and LWHA groups.
Maximum percent improvement in mean lameness scores was 56 percent in the HAIV group, 67 percent in
the LWHA group and 83 percent in the HWHA group (Graph 6 and Table 1). Other lameness variables
followed a similar pattern with several statistically significant findings in the HWHA group compared
to the PL group: for carpal circumference at post treatment weeks 3 and 8, stride length at post
treatment weeks 1-4, and carpal flexion at week 1. The HWHA group was also significantly better
compared to the HAIV group for carpal flexion at week 1.
Synovial fluid hyaluronate (HA) concentration decreased dramatically (87 percent) in response to
model induction. The HA concentration increased steadily after treatment, and all groups except the
PL group reached pre-model induction levels by about week 8. There was little correlation between
lameness scores and HA concentration. The MMWHA decreased an average of 42 percent after model
induction and improved post treatment in all drug-treated groups (Graph 7). Maximum improvement in
MMWHA for all drug-treated groups was noted at the same week that maximum improvement in lameness
score was recorded. For the HAIV group at week 6, lameness score was improved by 56 percent and MMWHA
was improved to 70 percent of pre-model induction levels. For the LWHA group, lameness improved 67
percent at post treatment week 8 and MMWHA had improved to 84 percent for pre-model levels. For the
HWHA group, the MMWHA had reached 116 percent of pre-model levels at post treatment week 8; maximum
improvement in lameness was 83 percent at post treatment week 12 and MMWHA was 123 percent of
pre-model baseline at week 12. At week 16, all groups were below pre induction baseline except for
the HWHA group, which remained at 104 percent of pre-model levels. Synovial fluid protein levels
increased in all groups after model induction and treatment had little effect on synovial fluid
protein. Necropsy and radiographic findings showed less degenerative bone and soft tissue changes
in the HWHA and LWHA treated horses versus the HAIV and PL horses.
Discussion: Although the small group sizes and inequities in exercise
levels in this experiment hampered our ability to achieve definitive statistical conclusions, some
significant findings along with distinct trends tend to support the following conclusions.
1. All exogenous SH preparations tested showed a degree of efficacy in this test system.
2. In general the intra-articular route of administration showed a higher degree of efficacy and
longer duration of action than did intravenous administration. It should be noted that only one
injection of each drug was administered.
3. There was a trend in both the clinical and laboratory data that supported greater efficacy for
HWHA versus LWHA. This trend may have been partially reduced by the increased amount of exercise
given the HWHA group horses.
4. There appears to be a distinct correlation between improvement in lameness scores and increases in
the MMWHA in the synovial fluid in horses treated with exogenous sodium hyaluronate.
GRAPH 1: HA Comparison Study
Group Mean Lameness Scores
Placebo group: No horse could be stressed on treadmill
HAIV Group: No horse could be stressed on treadmill
GRAPH 2: HA Comparison Study
Group Mean Lameness Scores
Placebo group: No horse could be stressed on treadmill
LWHA group: 1 horse could be stressed on treadmill
GRAPH 3: HA Comparison Study
Group Mean Lameness Scores
Placebo group: No horse could be stressed on treadmill
HWHA group: 3 horses could be stressed on treadmill
GRAPH 4: HA Comparison Study
Group Mean Lameness Scores
HAIV group: No horse could be stressed on treadmill
HWHA group: 3 horses could be stressed on treadmill
GRAPH 5: HA Comparison Study
Group Mean Lameness Scores
LWHA group: 1 horse could be stressed on treadmill
HWHA group: 3 horses could be stressed on treadmill
GRAPH 6: HA Comparison Study
Mean Maximum Percent Improvement in Lameness Score
The number in bracket is horses in group that could be stressed on treadmill (lameness score = 0).
GRAPH 7: HA Comparison Study
Mean Percent Recovery of MMWHA
TABLE 1: A Comparison of the Time to Maximum Percent Improvement of Lameness
Score With Time to Maximum Percent Recovery of the Model Induced Deficit in the Mean Molecular Weight
of Synovial Fluid Hyaluronate (MMWHA).
Treatment Group
HAIV
LWHA
HWHA
Max Percent Improv. in Lameness Score (Week)
56 percent (6)
67 percent (8)
83 percent (12)
Max Percent Recovery MMWHA (Week)
70 percent (6)
84 percent (8)
123 percent (12)
As with all intra-articular injections, occasional mild side effects may include heat,
transient edema and pain around the injection site. Most of these reactions are mild and should subside in 24–48 hours.
The author thanks and acknowledges the following people for their contribution to this study: Drs.
Chris Kawcak and Wayne McIlwraith, Orthopedic Research Laboratory, Colorado State University College
of Veterinary Medicine and Biomedical Sciences for synovial fluid analysis; Dr. Jack Hamm, Statistics
ByDesign for statistical analysis; Dr. Trent Stites, Sallisaw Animal Hospital.
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