Adequan, Legend and Cosequin

[Trish Dowling <dowling@skyway.usask.ca>]

The following is from a presentation I gave at the Alberta Horse Breeders Conference:

The chondroprotective drugs are used to prevent or slow the progression of degenerative joint disease (DJD, 
"arthritis"), rather than simply reduce the clinical signs of pain like the anti-inflammatory drugs. 
Chondroprotective drugs help the normal activity of chondrocytes (the cells in cartilage) and prevent or 
reduce damage to the joint cartilage from enzymes and other inflammatory mediators such as 
prostaglandins. 

Hyaluronan (HA), formerly known as hyaluronic acid, is a normal component of joint cartilage and fluid. It 
has been widely used as a treatment for joint diseases of people and horses.	Hyaluronan is chemically 
known as a nonsulfated glycosaminoglycan (contains no sulfur molecules). It is produced by the membrane 
that lines the joint capsule and disperses into the joint fluid and taken up by the joint cartilage. HA provides 
joint lubrication and protection of the joint cartilage from shear and compressive forces as the horse moves. 
It also reduces prostaglandin concentrations and scavenges free radicals in inflamed joints.
	Hyaluronan is primarily used in the treatment of degenerative joint disease (traumatic arthritis) of 
the carpal (knee), fetlock, coffin and hock joints of performance horses. Although cartilage damage is not 
always directly responsible for the horse's lameness, it is the limiting factor in rehabilitation of arthritic joints 
in the horse. It appears that HA concentration in joint fluid is reduced in degenerative joint disease. Injecting 
additional HA directly into the joint appears to normalize the joint fluid and increase the production of HA by 
the joint membrane. The actual injected HA remains in the joint for only a few hours, but its effect on the 
joint appears to last days to months. It does not appear that HA has any direct effect on joint cartilage.
	Clinical reports generally support the use of hyaluronan in the treatment of equine joint disease for 
reducing inflammation and lameness. In performance horses, a rapid return to work is a desirable outcome, 
and the action of HA has been considered a natural treatment without the risk of adverse effects associated 
with other treatments. Hyaluronan is effective for mild to moderate degenerative joint disease. For horses 
with severe degenerative joint disease, HA therapy alone is not adequate return them to athletic function.
	A formulation of HA for intravenous use has recently been approved in the Unites States (Legend) 
and Canada (Hyonate). This formulation provides a more convenient route of administration, allows for 
treatment of joints following injection of local anesthetic drugs without delay, and may reduce the adverse 
effects of intra-articular injections (bacterial infection, mechanical damage, drug-induced inflammatory 
reaction within the joint). It is not known how intravenously administered HA achieves therapeutic levels in 
the joint, but in a controlled study, horses treated with intravenously administered HA had a reduced degree 
of lameness compared to untreated horses.
	Intra-articular HA can be used in combination with other intra-articular medications such as 
corticosteroids. The combination therapy can result in a better and longer lasting improvement in lameness 
than either product alone.

	Adequan® is polysulfated glycosaminoglycan (PSGAG), made from an extract of cow lung and 
trachea that is then sulfated. The result is a large, charged molecule composed of galactosamine, 
glucosamine, and hexuronic acid. After administration, PSGAG binds to cartilage components. The precise 
mechanism of action of PSGAG in joints is unknown, but there are many studies demonstrating a beneficial 
effect of this product on damaged joints. Currently, PSGAG is thought to decrease destructive enzymes, act 
as an anti-inflammatory agent and stimulate the normal production of hyaluronan and glycosaminoglycans.
	Adequan® is indicated for the treatment of degenerative joint diseases. It is available in two 
formulations, one for intra-articular injection and one for intramuscular injection. When injecting directly into 
the joint, one 250 mg vial is used once a week for five weeks. When using the intramuscular injection, 500 
mg is injected every four days for four weeks. "Maintenance" therapy is not addressed by the manufacturer 
and has not been investigated in scientific studies, but veterinary practitioners have administered additional 
doses at intervals of weekly or monthly intervals with success in some horses.
	
Chondroitin sulfates/Glucosamines (Cosequin®, Flex Free®, Xtra-Flex, Glyco-flex®, etc)

	These chondroprotective products are sold as nutritional supplements - "nutriceuticals". The 
classification of nutriceutical means that these products are not considered as "drugs" and do not have to 
meet the same standards of purity, efficacy and safety that the FDA would require of a drug for the treatment 
of degenerative joint disease. The nutriceuticals are promoted as oral supplements supplying the horse with 
the "building blocks" necessary for repair of damaged cartilage. However, the building blocks for production 
of  joint cartilage are adequately supplied by most normal equine diets. There are many anecdotal reports of 
improvement in clinical signs of lameness in horses supplemented with nutriceuticals. However, 
well-designed scientific studies proving that these products are effective have not been published. Some of 
the nutriceutical manufacturers are sponsoring such studies and results are pending. These products appear 
to be safe, may improve a lameness condition, but are somewhat expensive for long-term therapy. Because 
the nutriceuticals are not regulated by government agencies in the same manner as a drug would be, there 
is considerable variation in the composition and purity of the available products. Therefore, clinical results 
may vary considerably between the products.
	The condroprotective nutriceuticals usually contain glucosamine salts and/or chondroitin sulfate. 
Cartilage cells normally synthesize glucosamine from glucose and amino acids, however they can also use 
externally supplied, preformed glucosamine. Regardless of the source, the cartilage cells use glucosamine 
to synthesize glycosaminoglycans and hyaluronan. Glucosamine also regulates cartilage synthesis of 
proteoglycans and collagen.
	Chondroitin sulfate (CS) is long chain molecule composed of galactosamine sulfate and glucuronic 
acid units. It is the predominant glycosaminoglycan found in joint cartilage and is a natural component of 
other tissues, including tendons, bone, vertebral discs, heart and cornea. Chondroitin sulfate stimulates 
glycosaminoglycan and proteoglycan synthesis in joint cartilage. It also inhibits destructive enyzmes in joint 
fluid and cartilage.

On my own horses, I will use HA on an early problem, where I do not see changes on the x-rays. Here, an 
intravenous dose of HA costs $150/dose and you give three doses. I will use Adequan with a more chronic 
problem where I do see changes on the x-rays. Here, each dose of Adequan costs $70 and you give 7 
doses. We only have a few brands of nutriceuticals in Canada, and they cost about $100 a month to keep a 
horse on them. At this time, I have not seen enough scientific proof that these products work that I am 
willing to spend that amount of money.

Cheers,
Trisha
Trisha Dowling, DVM, MS, Diplomate ACVIM & ACVCP
Associate Professor, Veterinary Clinical Pharmacology
Western College of Veterinary Medicine
Saskatoon, SK S7N 5B4
306-966-7359/FAX 306-966-7376