This report details a breakthrough in laminitis prevention that is the first such strategy to be scientifically validated both experimentally and clinically. The report also contains “state of the art” information on foot anatomy, pathology, prevention and treatment that will help the reader understand laminitis and thus make better decisions for the animals in their care. New discoveries about how laminitis is triggered lay the foundation for the development of new, targeted treatment regimens.

Who is the report targeted at
This report will inform horse owners, veterinarians, technicians, animal scientists, farriers, trainers and the horse industry in general about the new laminitis preventive strategy and how and when to implement it. It contains guidelines for the therapeutic shoeing of existing cases of laminitis and suggestions for managing animals at risk of developing the disease. The report is written in non technical language; scientific reports are listed for those requiring more detailed information.

Background
Laminitis is the most serious disease of the equine foot and causes pathological changes in anatomy that lead to long lasting, crippling changes in function. It is the second biggest killer of all horse breeds after colic. Due to both its devastating nature and lack of effective therapies, equine laminitis has been listed as a priority for equine research by numerous equine organizations and funding agencies including the RIRDC. The pathophysiology of laminitis has been unclear and controversial for several decades, which is most likely the reason for the overall failure of the majority of drugs that have been introduced to treat the disease. Data generated by RIRDC sponsored laminitis research suggest that the primary triggering event is uncontrolled matrix metalloproteinase (MMP) activation and inhibiting this, to prevent/treat the disease, as we proposed in 1998, has been the focus of this project.

Methods used
The methods used in the RIRDC laminitis projects range from basic clinical observations to the use of most sophisticated molecular genetic probes available. Images were obtained by light microscopy, immuno-fluorescence microscopy, electron microscopy, digital radiography and computed tomography (CT) scanning. Laminitis source material came from natural field cases as well as a small number of experimental cases induced under strict ethical guidelines. A hoof explant protocol was developed that enabled the study of laminitis in the laboratory in vitro. Double blind assessment of data by independent observers, rigorous statistical analyses and validation by up to three independent methods ensured correct interpretation of experimental results.

Results/key findings
The in vitro model for laminitis using hoof explants, followed by zymographic analysis of enzymes, showed that activation of MMP-2 and MMP-9, by laminitis or chemically, resulted in separation of hoof epidermal and dermal lamellae. Increased gene transcription of MMP-2, MMP-9 and MMP-14 was present during laminitis. The presence of an MMP inhibitor, BB-94, blocked the activity of the MMPs in vitro a result highlighting the potential such drugs have as preventive and treatment agents of the future. A sugar-like ingredient in grass called fructan was able to initiate laminitis experimentally thus explaining why pastures high in fructan may sometimes precipitate the disease. In the horse’s hindgut, the presence of excess fructan produces an environment that favours the rapid proliferation of Gram-positive bacteria that produce lactic acid and a range of toxins. Factors present in the supernatant of cultures of these bacteria activated MMP-2 and caused lamellar separation in vitro indicating that in addition to intrinsic trigger factors a microbial influence may also play a role in laminitis development.

Horses and ponies affected by Equine Metabolic Syndrome are often obese, have cresty necks and increased adipose tissue deposits in the withers and dorsal area of the back. Plasma insulin concentrations above 100 ?IU/ml indicate insulin resistance (hyperinsulinaemia) and a high risk of laminitis. Insulin alone, when administered in excess to normal ponies, caused laminitis.

Management strategies that control insulin resistance and carbohydrate intake decrease the likelihood of laminitis Early clinical signs of laminitis include shifting weight from one foot to the other, high hoof temperatures for a prolonged time and bounding pulses in the digital arteries. After the development of more extensive lamellar pathology, foot pain increases. Its severity is proportional to the extent of displacement of the distal phalanx within the hoof capsule. A characteristic stance and gait is adopted by the horse to minimize the pain in its feet. Chronic laminitis is marked by persistent lameness and anatomical disintegration of the hoof that includes changes to the coronary band, the development of a dropped sole and deformed hoof growth. Radiographic and venographic examination of the feet should be performed as soon as clinical signs of laminitis appear and during the course of treatment.

Inward growing tubular hoof is destructive and contributes to rotation and lysis of the distal phalanx.

Radiographs that supply information on the position of the distal phalanx and hoof distal phalangeal distance (HDPD) should be obtained with careful radiographic technique to allow early diagnosis and treatment. The rate at which the HDPD increases and the appearance of a radiolucent line beneath the inner hoof wall are indicators of the severity of the lamellar pathology. When the distal phalanx sinks rapidly into the hoof capsule, without rotation, the cases are labelled “sinkers” and have catastrophic outcomes. With increasing chronicity, the degree of palmar rotation and pathology of the distal phalanx should be determined radiographically.

Venography is possible because there are no valves in the veins of the horse’s foot. Performing a venogram is relatively simple, but requires practise and good radiographic technique. Venograms provide more information than plain radiographs especially if performed sequentially. Venograms diagnose venous filling problems due to progressive pathological changes in tubular hoof wall and sole growth.

Implications and recommendations for horse care-givers
The new knowledge about laminitis, contained in this report, will help equine care-givers to better understand the disease and make rational, informed decisions regarding prevention and treatment and if necessary euthanasia. Vigorous treatment of the primary inciting disease is of paramount importance. The diagnosis of toxaemia and septicaemia is associated with a high risk of developing laminitis and requires the initiation of medical therapy and mechanical support for the distal phalanx before the appearance of clinical signs of hoof pain. Inflammation and foot pain can be reduced with anti-inflammatory drugs, however their effect is only palliative and will not stop the development of laminitis. Cryotherapy is a proven preventive for horses at risk of developing laminitis, while vasodilator therapy and forced exercise are contraindicated. The administration of mineral oil or activated charcoal may be beneficial in cases of laminitis developing after ingestion of excess grain.

Effective mechanical support, using frog/sole support devices, should be provided early to a horse developing laminitis to improve the outcome of the disease. Cooperative liaison between horse owner, veterinarian and farrier is required for correct application of therapeutic shoes. A supportive sole cast, made using a two-part silicone based impression material, provides additional support to the back part of the foot. Strategic proximal and distal toe hoof wall resection reverses the abnormal hoof growth due to chronic laminitis.

Recovery from laminitis is unpredictable, but generally the prognosis is directly proportional to the extent of displacement of the distal phalanx and the resultant lamellar pathology that occurs. The return to a normal-looking hoof takes time and prolonged aftercare will often be required. Few horses return to their former athletic soundness after chronic laminitis.

Research at the Australian Equine Laminitis Research Unit (AELRU) is devoted to discovering the mechanism by which the hoof lamellae separate, because prevention of this terrible disease represents a better option than trying to repair the gross anatomical dislocations once they have occurred. Much progress has been made and the research team is ready to embark on preventive and treatment modalities based on the new knowledge gained by the RIRDC sponsored laminitis research of the last nine years.