Double Blind Study of the Effects of CORTA-FLX in
Report submitted by: Hilary M. Clayton, BVMS, PhD, MRCVS
In recent years, the use of oral supplements that are intended to support joint health has become very popular for relief of the symptoms of degenerative joint disease (DJD) in people and animals. There is considerable anecdotal evidence to support the use of these products, together experimental evidence of their efficacy in treating DJD in horses (1).
DJD is the most common joint disease in horses. Therapy is directed towards providing analgesia, controlling inflammation (if present), limiting damage to articular tissues and promoting healing of damaged cartilage. Medical treatment is usually based on non-steroidal anti-inflammatory drugs and/or corticosteroids to relieve pain, reduce lameness and suppress inflammation. Long term use of these medications, however, may suppress chondrocyte metabolism and inhibit normal collagen and proteoglycan synthesis leading to further degradation of the cartilage matrix. Disease modifying drugs, which include polysulphated glycosaminoglycan and hyaluronan, also have anti-inflammatory and analgesic effects. Feed supplements designed to support joint health may also be disease modifying though there have been limited studies to support or refute their efficacy in treating DJD.
Traditionally lameness is evaluated subjectively and graded on a five-point scale (2). Gait analysis is an objective tool for measuring gait. It uses kinematic variables to describe the movements of the segments and joints and kinetic variables to describe the forces associated with locomotion. Ground reaction forces, which are usually resolved into vertical and horizontal (shear) components, measure the forces between the hoof and the ground. Summation of the ground reaction force throughout the stance phase is the impulse. Kinematic and force variables are used to calculate the torque (turning force) around each joint and the bursts of mechanical energy absorption and generation. Energy absorption is indicative of the function of the joint in absorbing concussion; energy generation is indicative of the provision of propulsion.
Even for experienced clinicians, subjective scoring of mild to moderate lameness is not very repeatable in comparison with kinematic analysis (3). Therefore, objective gait analysis is the preferred technique for evaluating changes in the degree of lameness over time. However, it is important to select a set of variables that are consistent with the objectives of quantifying lameness. Vertical ground reaction force (GRF) represents the weight-bearing function of the limb, with peak vertical force and vertical impulse being the most useful measurements. Redistribution of the vertical GRF between the limbs is indicative of changes in the willingness to bear weight on different limbs, which is a relevant consideration in supporting limb lameness (4). Joint kinematics have been described in horses with various lamenesses (5). Net joint torques and mechanical energy profiles across a joint have received less attention to date, but may prove more sensitive to changes in the degree of lameness than the kinematic or GRF variables (6).
Velocity affects the gait variables, and lame horses tend to move more slowly as a means of reducing pain by decreasing the GRFs (7). Therefore, it is important to ensure that horses move at the same velocity if the objective is to compare signs of lameness at different times. In this study, trials were saved in which the horse moved at a pre-selected velocity that was scaled to the horse’s height and weight (8). It might be argued that a voluntary increase in velocity is a sign of reduced lameness – however, this is a subjective evaluation rather than an objective measurement. It is unlikely that horses will show significant changes in stride length while being constrained to move at constant velocity.
The goal of this study was to assess changes in gait variables objectively in horses with tarsal degenerative joint disease after administration of CORTA-FLX in a double-blind placebo-controlled trial.
Materials and Methods
The study was a double-blind placebo-controlled study designed to test the effects of CORTA-FLX on gait symmetry of lame horses. The eight subjects were riding horses that were in regular use, being ridden 4 to 6 days per week. All horses showed a mild/moderate (Grade 1 or 2) in one or more limbs. All were diagnosed as having tarsal joint DJD (bone spavin) in one or both hind limbs on the basis of physical examination, diagnostic anesthesia, and radiography. In addition, some of the horses had other lamenesses (Table 1), which is usually the case in horses with DJD.
The active CORTA-FLX solution and a placebo were supplied in bottles identified only by numbers 1 through 16. The placebo solution was indistinguishable from the active solution in taste, smell, color and consistency. Horses were admitted into the study in pairs and were numbered sequentially so there was an odd and an even-numbered horse in each pair. Horses #1, 3, 5, and 7 received the odd-numbered treatment solution first, and horses #2, 4, 6, and 8 received the even-numbered treatment solution first.
The owners were instructed to with-hold all dietary supplements and medications, commencing two weeks before the start of the study, and continuing until after the study was completed. After the initial 2 week stabilization period, horses received the first treatment orally for 2 weeks, followed by 2 weeks without treatment and then the alternative treatment was administered orally for 2 weeks. During each treatment period, the horses received a loading dose of 60 ml/day for 5 days, followed by a maintenance dose of 30 ml/day for 9 days.
Gait analysis was performed using standard methods as the horses trotted in hand along a rubberized runway. Briefly, reflective spheres were attached over the centers of rotation of the hip, stifle, tarsal, fetlock and coffin joints and the distal hoof wall at the toe and heel. These markers were tracked automatically by a six camera infra-red system recording at a frame rate of 120 frames/s. The marker locations were used to determine joint angles during the stance phase of the stride. Ground reaction forces were collected synchronously with the kinematic data using a 60 x 120 cm2 force plate that was embedded in the rubberized runway. Gait analysis was performed at the completion of each 2 week treatment period. The horses moved at the same velocity during each evaluation, with the appropriate velocity for each horse being determined according to its height and weight (8).
Variables for analysis were selected based on the researchers’ experience and published literature indicating which variables are sensitive to changes in the degree of tarsal joint lameness. The following variables were measured for the left and right fore and hind limbs during the stance phase of the trot:
A symmetry index was constructed for each variable using the values measured for the left and right limbs: the lower value was divided by the higher value, so the index is always less than one. This index provided an indication of contralateral limb symmetry without differentiating between the left and right limbs. The higher the value (closer to unity) the greater the left-right symmetry for the variable under study. The treatment code was broken after completion of the data reduction.
Comparisons between the symmetry indices for each variable after treatment with the two solutions were made using paired samples t-tests with a probability level of P<0.05.
In addition, the total vertical impulse for the two hind limbs was determined as an indication of the total weight-bearing by the hind limbs. It was calculated by summation of left hind limb vertical impulse and right hind limb vertical impulse. Paired t-tests were used to compare the weight-bearing by the hind limbs following treatment with CORTA-FLX and the placebo. If the total amount of weight borne by the hind limbs did not change, but the symmetry index for peak vertical force or vertical impulse increased, it was indicative of a more symmetrical weight distribution. A reduction in total vertical impulse would indicate an overall weight shift to the forelimbs.
The velocities did not differ between groups (placebo solution: 3.26 ± 0.16 m/s; active solution: 3.27 ± 0.16 m/s). The total vertical impulse summed over the left and right hind limbs was the same for the two evaluations. The symmetry indices for the individual horses are shown in figure 1. Compared with the placebo, treatment with CORTA-FLX resulted in significant increases in left-right symmetry of vertical GRF (P= 0.023), tarsal joint range of motion (P=0.005) and tarsal joint energy generation during stance (P=0.043). These changes, which were consistent across horses, are summarized in figure 2. The other variables did not change significantly, but the vertical impulse (P=0.080) showed a trend toward greater symmetry after treatment with CORTA-FLX. In horse 2, symmetry of tarsal joint energy absorption was markedly lower following treatment with CORTA-FLX, which had a marked effect on the statistical analysis. This was the result of an inconsistent kinematic pattern in the left hind limb, which may have been related to the presence of a bone chip in the fetlock joint of that limb.
Visual assessment of lameness is based on observation of a complex array of clinical signs that are indicative of asymmetrical or abnormal movement patterns. Gait analysis of lame horses offers a means of quantifying the movements and associated forces in a repeatable and quantitative manner. The use of left-right asymmetries as a means of assessing the severity of lameness is well recognized and various symmetry indices have been developed. Symmetry indices have been applied in analysis of kinematic variables (9) and ground reaction forces (10).
In the study reported here, every effort was made to ensure an objective and quantitative evaluation by using a placebo control, blinding the researchers and the owners to the order of treatment, and using objective measurements of gait analysis. Subjects were selected that were typical of the type of horses that are treated with CORTA-FLX in the field. They were mature horses that were in regular work and that had DJD in multiple sites. DJD is a common pathology in older working horses and the majority of affected horses show changes in more than one joint. The fact that the horses used in this study were lame in multiple sites produced complex patterns of gait abnormalities and compensations, which are typical of the older working horse. However, the presence of multiple pathologies complicates the clinical evaluation and the gait analysis. However, the use of symmetry indices provided a better method of assessing the overall lameness.
The gait variables chosen for analysis represented the weight-bearing function of the hind limbs and the movements and functions of the tarsal joint. The results clearly indicated that CORTA-FLX produced a more symmetrical gait pattern at the tarsal joint in horses with tarsal DJD, which was interpreted as being indicative of an improvement in locomotor function. It is unrealistic to expect that a feed supplement will restore complete soundness, but an effective product might be expected to improve the lameness so that the horse’s gait pattern more closely approaches left-right symmetry.
The treatment period of 2 weeks was quite short, but there is evidence of a rapid improvement in clinical signs following the administration of CORTA-FLX. A previous study of the effects of a this product in horses with DJD showed that lameness grade, flexion test grade and stride length improved rapidly during the first 2 weeks of administration, and then more slowly during the following 2 weeks (1).
It is concluded that the gait pattern at the trot became more symmetrical in horses with tarsal DJD after they received CORTA-FLX compared with administration of a placebo.
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