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Dr. Victoria Maxwell, DVM, MBA, Luitpold Pharmaceuticals, Inc. Degenerative joint disease (DJD) = osteoarthritis Why we see DJD in young horses • Rigors of “use trauma” allow the forces of destruction to outweigh normal repair Two long bones together = diarthual joint • Range of motion anterior/posterior aka forward/backward • External support structures – skin, tendon, ligaments • Joint capsule – extends from one end of long bone to the end of the other long bone • Synovial membrane – windpuffs (synovitis = inflammation of synovial lining) • Articular cartilage (AC) – hyperhydrated gel on the ends of the long bones, provides shock radiation for the joint, the thicker the AC the better! • Subchondral bone – right under the AC • Joints are avascular – don’t have a very good blood supply HA = hyron = hyronic acid – from blood plasma synoviocytes pull this plasma in to the AC AC • Proteoglycan complex Chondroid sulfate, Keratin sulfate and HA o Think of the complex as Christmas garland the coiled strands of tinsel are made up of HA with chondroid sulfates and keratin sulfate. o The two sulfates repel each other (both have a negative charge), this creates the o Chondrocytes are in charge of creating these complexes for rebuilding AC • Heat • Pain • Swelling • Redness • Loss of function Arthritis pathophysiology Aggrecan (proteoglycans) + degradative enzymes → matrix damage → cartilage erosion FDA approved drugs/Center of Veterinary Medicine approved drugs • Non-steroidal anti inflammatory drugs (NSAID) o Bute (bone), Banamine (soft tissue), Ketafen, Arquel, Surpass, Fibrocoxx (gut • Corticosteroids (suppress repair as well as pain) “Solution to the pollution is dilution” – think your craving for water after a hard night of drinking. Body needs water to dilute the alcohol (pollution) in its system. Joints do that too, push water into the joint to rehydrate and improve function. Goals of therapy • Suppress inflammation • Repair and prevent articular damage • Stimulate synthesis of collagen, HA and proteoglycans • Return to normal function/career Preservation of long term joint function Adequan – super sulfated big fat repeating sugar (GAG) Arteparon – human formula 1950s in Germany looking for molecule for treatment for Leukemia aka blood cancer • Side effect improved arthritis suffering in the elderly who took the drug for Leukemia • The creators took another look at the formulation of the drug and discovered it had a tremendous impact in the chondrocytes in AC • First developed as an antithrombic due to its heparin like effect on blood coagulation • A vet in New York brought some to the States and was injected in racehorses was called German Acid, these horses had very long racing careers and remained sound Company realized there was a market in veterinary medicine so Adequan was born in 1983, same formula. • Made by extracting chondroitin sulfate from bovine trachea in Green Bay, WI (FDA approved raw material facility), sent to France where it is highly sulfated (they ad 3 more), sent back here for distribution. • Takes 24 months for a bottle to be made, 70 step process, 7 are highly critical Horse and dog use first described in 1966 Rapidly absorbed after intramuscular injections with peak blood concentrations in 20/30 minutes Peak levels in synovial fluid occur within 2 hours of injection Peak levels in articular cartilage occur within 24/48 hours 80% of the drug stays in the AC Therapeutic levels persist in cartilage for about 96 hours in AC Farm has breeding stock of 85 with one major stallion and have 30% of foal crop having Osteochondritis Dessecans (cartilage that has a hole in the middle, think doughnut). The problem with the hole is there is no cushion for shock to radiate off of; it all passes through the opening down through the bones causing bruising. • Year 1 – year before study started 85 foals born 22 went to surgery for OCD • Study Year 1 – 85 foals were put on Adequan every 4 days for a month, off a month, on every 4 days for a month, off a month, and again on every 4 days for a month; 2 foals went to surgery. This was great the farm was happy but felt giving injections twice a week was too much for the staff and the foals. • Study Year 2 – decided to dose once a week instead of twice, same monthly format; 83 • Findings – Adequan worked best when used in its original prescribed manner. • Pay focus to your horse’s leg, check for heat daily by using the back of your hand. • Written or video (trot to, away and side once a month) • “Coach’s EYE” video app • Inhibition of AC matrix degeneration blocks inflammation enzymes • Stimulate production of cartilage matrix components reverse cartilage deterioration • Improves synovial lubrication – double HA concentration in 48 hours • Decrease inflammation • Relieve pain • Is legal in all disciplines in all counties at all levels of competition, since it is a naturally FDA classified as Chondroprotective drug o Disease Modifying Osteoarthritic Drug (DMOAD) o Adequan and Legend are DMOADs • Intravenous or intramuscular injection • Difference between Adequan and Legend o Legend – treats the soft tissue part of the joint (treats synovitis) o Adequan – treats the boney/cartilage part of the joint • Pharmacological and pharmacokinetic behavior very consistent in several species o Extra label use in various species (dog all the way to elephant and everything in • Is a drug that should be included in the arsenal of addressing synovitis and osteoarthritis • Don’t wait for advanced stages of the disease process to turn back pathophysiology, utilize the drugs available by understanding the disease process.

Source: http://arabinc.org/Docs/DJDNotes.pdf