Response to Corta-Flx in Horses with Tarsal Degenerative Joint Disease: A Double Blind Study Hilary M. Clayton, BVMS, PhD, MRCVS, Patricia E. Almeida, MS, DVM, Marta Prades, DVM, Dip ACVS, Dip ECVS, Jennifer Brown, DVM, Caroline Tessier, DVM, and Joel L. Lanovaz, BS, MS Mary Anne McPhail Equine Performance Center Department of Large Animal Clinical Sciences College of Veterinary Medicine Michigan State University East Lansing, MI 48824 Summary The objective was to quantify the response to treatment with an oral supplement in horses with tarsal degenerative joint disease. A double-blind protocol was used in which Corta-Flx or a placebo were administered daily by mouth for two weeks. The response was evaluated using kinematic and kinetic gait analysis. Left-right symmetry of gait variables was determined, and an increase in symmetry was interpreted as a positive finding. There were significant increases in symmetry of tarsal joint range of motion, peak net joint extensor moment, peak power absorption, peak power generation ***** after Corta-Flx compared with placebo treatment. Abstract A double blind study showed that treatment with Corta-Flx resulted in significant improvement in left-right symmetry of tarsal joint motion, tarsal joint torques and mechanical energy generation and absorption at the tarsus compared with placebo treatment. Introduction Degenerative joint disease is a common problem of aging athletes, human and equine (REFS). Oral supplements intended to support joint health and reduce the discomfort and pain associated with degenerative changes are consumed in large quantities, and there is considerable anecdotal evidence to support the use of these products. To date, experimental evidence of their efficacy in treating degenerative joint disease in horses is limited. ** describe studies in horses(1). Treatment of degenerative joint disease in horses is directed towards providing analgesia, controlling inflammation (if present), limiting damage to articular tissues and promoting healing of damaged cartilage. Non-steroidal anti-inflammatory drugs and/or corticosteroids are administered to relieve pain, reduce lameness and suppress inflammation, but long term use of these medications may suppress chondrocyte metabolism and inhibit normal collagen and proteoglycan synthesis leading to further degradation of the cartilage matrix (ref). Disease modifying drugs, such as polysulphated glycosaminoglycan and hyaluronan, are beneficial due to their anti-inflammatory and analgesic effects. Oral supplements designed to support joint health may also be disease modifying, in addition to having anti-inflammatory effects. There is some evidence suggesting that clinical signs improve rapidly in response to administration of oral supplements that support joint health. A glucosamine-chondroitin sulfate compound produced improvements in lameness grade, flexion test grade and stride length within 2 weeks in horses with degenerative joint disease (1). During physical examination, lameness is graded on a five-point scale (2). Visual assessment of lameness is highly subjective and, as such, is dependent on the experience and acuity of the clinician. More experienced clinicians are more consistent in their evaluations than residents or interns (REF). Gait analysis offers an objective method of assessing lameness. In general, studies comparing clinical lameness evaluation with the results of gait analysis have shown good agreement with regard to the affected limb, but less correlation in grading the degree of lameness (REFS). Gait analysis is an objective tool for measuring gait. Kinematic variables describe the movements (angulations) of the segments and joints and kinetic variables describe the forces responsible for the movements. The ground reaction force vector represents the force between the hoof and the ground. It is resolved into vertical and horizontal (shear) components. Summation of the ground reaction force over a period of time is the impulse. Kinematic and force variables are used to calculate the net joint moment (torque or turning force) around each joint and the bursts of mechanical energy absorption and generation. Energy absorption occurs during eccentric muscular contractions and indicates that the joint is absorbing concussion; energy generation occurs during concentric muscular contractions and indicates the provision of propulsion. Gait analysis produces an over-whelming number of variables, not all of which are useful for every study. It is important, therefore, to select and analyze a set of variables that are consistent with the objectives of the study. Vertical ground reaction force (GRF) represents the weight-bearing function of the limb, with peak vertical GRF 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, and this is a relevant consideration in analysis of supporting limb lameness (4). Joint kinematics describe the movement patterns and have been applied in horses with various lamenesses (5). Net joint torques and mechanical energy generation and absorption across a joint have received less attention to date, but may prove to be more sensitive to changes in the degree of lameness than kinematic or force variables (6). Many gait variables are velocity dependent, so it is important to control velocity if comparisons are to be made within a horse on different occasions. Lame horses tend to decrease their velocity as a means of reducing pain by decreasing the ground reaction forces (7). In this study, trials were analyzed in which the horse moved at a pre-selected velocity that was scaled to the horse’s height and weight (8). The objective of this study was to assess changes in gait variables objectively in horses with tarsal DJD after administration of a joint supplement in a double-blind placebo-controlled trial. Materials and Methods Subjects A double-blind placebo-controlled design was used, and all the assessment criteria were objective measurements. The ten subjects were in regular work, being exercised at least four days per week. Horses were selected for inclusion in the study based on the results of clinical and radiographic findings and the response to diagnostic anesthesia. Criteria for inclusion were a Grade 1 or Grade 2 lameness in one or both hind limbs, radiographic evidence of degenerative joint disease in the distal inter-tarsal and/or tarsometatarsal joints, and an improvement in lameness following intra-articular anesthesia of the affected joint(s). Some horses also had degenerative joint disease in other joints of the fore or hind limbs (table 1). Oral Supplements The oral supplement used in the study contained guaranteed levels of manganese, copper, sulphur, vitamin B-6, ascorbic acid, glutamine, proline, glutamic acid, glycine and glucuronic acid, together with animal protein products, methionine, alanine, arginine, aspartic acid, tyrosine, serine, valine, phenylalanine, histidine, threonine and isoleucine. Both the Corta-Flx solution and the placebo solution contained xanthan gum as a thickening agent, sodium benzoate as a preservative and yucca as a natural flavoring agent in an aqueous base containing dextrose, corn syrup and sorbithol. The placebo solution was indistinguishable from the active solution in taste, smell, color and consistency. The two solutions were provided in numbered bottles. The treatment code was broken after completion of the data reduction. Study Design Horses entered the study in pairs and were numbered sequentially so there was an odd and an even-numbered horse in each pair. Owners were instructed to with-hold dietary supplements and medications from two weeks before the study began until after the study was completed. Horses received their first treatment orally for 2 weeks, followed by 2 weeks without treatment and then the alternative treatment was administered orally for 2 weeks. Odd numbered horses received an odd-numbered bottle first and an even-numbered bottle second. Even-numbered horses received an even-numbered bottle first and an odd-numbered bottle second. The solutions were administered orally using a dosing syringe. During each treatment period, a loading dose of 60 ml/day was given for 5 days, followed by a maintenance dose of 30 ml/day for 9 days. Data Collection and Analysis Gait analysis was performed at the completion of each 2 week treatment period with the horses moving at constant velocity, with the appropriate velocity for each horse being determined according to its height and weight (8 - Khumsap). Reflective spheres, 2.25 cm in diameter, were attached to the skin over the tuber coxae, the centers of rotation of the hip, stifle, tarsal, fetlock and coffin joints and the distal hoof wall at the toe and heel. Since the anatomical landmarks that identify the coffin joint cannot be palpated directly, a lateral radiograph of the hoof was used to identify the actual location of the coffin joint relative to the three hoof markers. The position of the coffin marker was then adjusted during post-processing using a triangulation technique. The skin markers were tracked automatically with a sampling rate of 120 Hz by a six camera Expert Vision Real Time System (Motion Analysis Corp., Santa Rosa, CA) as the horses trotted in hand along a rubberized runway. Immediately after each trial was completed the velocity was checked and only those trial that were within the predetermined range were accepted. The digitized marker locations were used to determine limb segment angles and joint angles during the stance phase of the stride. The kinematic variables calculated during the stance phase were: limb protraction and retraction, tarsal joint range of motion, and metatarsophalangeal joint range of motion. Ground reaction forces (GRFs) were collected synchronously with the kinematic data using a 60 x 120 cm2 force plate (Advanced Medical Technology Inc., Watertown, MA) sampling at 1,200 Hz. The force variables measured were: peak vertical GRF, vertical impulse, *** Inverse dynamic analysis (REF) was used to calculate peak tarsal joint torque during the stance phase, and mechanical energy absorption and generation across the tarsus during stance. 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 was 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. Statistical Analysis Comparisons between the symmetry indices for each variable after treatment with Corta-Flx versus the placebo solution were made using paired samples t-tests with a probability level of P<0.05. Results The mean velocities did not differ between evaluations (placebo solution: 3.23 ± 0.14 m/s; Corta-Flx: 3.24 ± 0.15 m/s). The total (left + right) vertical impulse did not differ significantly between placebo and Corta-Flx treatments, indicating that the total amount of weight carried by the two hind limbs did not change. However, the vertical impulse was distributed more symmetrically between left and right hind limbs after treatment with Corta-Flx compared with the placebo (P=0.025). Tarsal joint range of motion (P=0.005) and tarsal joint energy generation during stance (P=0.017) were more symmetrical after Corta-Flx than placebo. The net joint moment peak and the net energy absorption at the tarsus did not change significantly, but the symmetry indices increased in /10 and /10 horses, respectively. Symmetry indices for the measured variables are shown in Figure 1. .Figure 1: Symmetry indices for gait variables after treatment with placebo solution (dark bars) or Corta-Flx® (light bars). Values are means of 10 horses. Asterisks indicate values that differ significantly (p<0.05). Table 1: History and lameness diagnoses in horses used in study. Horse Age (years) Sites of Degenerative Joint Disease Tarsal Joints Other sites 1 8 Left 2 12 Left and right Bone chip LH fetlock Bilateral navicular changes 3 aged Left and right 4 20 Left Left and right fore fetlocks 5 19 Left and right Left and right fore fetlocks 6 19 Left 7 11 Left 8 aged Left and right 9   10   Discussion The horses used in this study were selected as being typical of the population of athletic horses in which degenerative joint disease is a common pathology and in which oral supplements designed to support joint health would be most beneficial. They were sound enough to be in regular work without medication, yet sufficiently lame that they received a score of Grade 1-2 on physical examination. Horses that fit this model are often lame in more than one limb or at more than one site within a limb leading to complex patterns of gait abnormalities and compensations. Case selection was based on the presence of tarsal degenerative disease, but horses that also had degenerative changes in other joints were not screened out. The premise was that, if Corta-Flx reduced the pain associated with degenerative joint disease, treatment would produce an overall improvement in locomotion compared with the placebo. The variables chosen for analysis represented the weight-bearing function of the hind limbs (vertical force and impulse) and freedom of movement (range of limb protraction), together with variables that are more specific to the tarsal joint (range of motion, peak net joint moment, net joint energy absorption and generation). The results clearly indicated that treatment with Corta-Flx for two weeks produced a more symmetrical gait pattern, which was interpreted as being indicative of an improvement in locomotor function. It is unrealistic to expect that an oral supplement of this type 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. Several research studies have used indices of left-right symmetry as a means of assessing the severity of lameness (REFS). Symmetry indices have been applied in analysis of kinematic variables (9) and GRFs (10). *** HAAS, head nod, BCM Assessment of the results of this study was complicated by the fact that some of the horses were lame in more than one limb. The use of a non-directional symmetry index proved useful for expressing the return toward a more symmetrical gait pattern, regardless of the relative improvement in left and right limbs. The value of a symmetrical gait pattern is that it is perceived by a veterinarian, trainer or judge as an improvement in the horse’s locomotion and is thus representative of restoration of the horse’s suitability for athletic pursuits. Thus, the use of symmetry indices is appropriate to the goals of this study, which were to determine whether treatment with Corta-Flx was useful for decreasing lameness in horses with mild lameness due to degenerative joint disease. The study was made as objective as possible by using a placebo control, by blinding both the researchers and the owners to the order of treatment, and by relying on objective measurements of locomotor performance. It is concluded that the gait pattern at the trot became more symmetrical in horses with degenerative joint disease after treatment for two weeks with Corta-Flx, an oral supplement designed to aid joint health. References 1. Hanson RR, Smalley LR, Huff GK et al. Oral treatment with a glucosamine-chondroitin sulfate compound for degenerative joint disease in horses: 25 cases. Equine Pract 1997;19:16-22. 2. Kester WO. Definition and classification of lameness. In: Guide for veterinary services and judging of equestrian events. 4th ed. American Assoc Equine Practnr1991;19. 3. Keegan KG, Wilson DA, Wilson DJ et al. Evaluation of mild lameness in horses trotting on a treadmill by clinicians and interns or residents and correlation of their assessments with kinematic gait analysis. Am J Vet Res 1998;59:1370-1377. 4. Merkens H and Schamhardt HC. Evaluation of equine locomotion during different degrees of experimentally induced lameness II: Distribution of ground reaction force patterns of the concurrently loaded limbs. Equine Vet J Suppl 6:107-112. 5. Buchner HHF, Savelberg HHCM, Schamhardt HC et al. Limb movement adaptations in horses with experimentally induced fore or hind limb lameness. Equine vet J 1996;28:63-70. 6. Clayton HM, Schamhardt HC, Lanovaz JL, et al. M.A. Net joint moments and joint powers in horses with superficial digital flexor tendinitis. Am J Vet Res 2000;61:197-201. 7. Clayton HM, Willemen MA, Schamhardt HC, et al. Kinematics and ground reaction forces in horses with superficial digital flexor tendinitis. Am J Vet Res 2000;61:191-196. 8. Khumsap S, Clayton HM and Lanovaz JL. Effect of walking velocity on hind limb ground reaction force variables in the hind limb of clinically normal horses. Am J Vet Res 2001;62:901-906. 9. Pourcelot P, Audigié F, Degueurce C et al. Kinematic Symmetry Index: a method for quantifying the horse locomotion symmetry using kinematic data. Vet Res 1997;28:525-538. 10. Merkens HW, Schamhardt HC, Hartman W et al. The use of H(orse) INDEX: A method of analysing the ground reaction force patterns of lame and normal gaited horses at the walk. Equine vet J 1988;20:29-36. Acknowledgements This study was funded by Nature’s Own, Inc., Aiken, SC.