Lameness is the principal reason for time lost to training in all horse sports. The most common cause of lameness is joint pain. The physiology of joints is such that any insult, including "use trauma" will result in metabolic dysfunction and may trigger the self-perpetuating, vicious cycle of degenerative joint disease (osteoarthritis).

The synovial lining of the joint secretes inflammatory products in response to injury, as well as excess joint fluid with low viscosity. The inflammatory products, such as superoxide radicals, lysosomal enzymes, nitric oxide and gelatinase damage the cartilage and cause further inflammation. The excess joint fluid increases, stretching the fibrous joint capsule, causing pain and worsening the inflammatory response.

The central feature of degenerative change in joints is loss of glycosaminoglycans from articular cartilage. The availability of glucosamine (like that provided by Top Form Joint Supplement) is a rate-limiting step in glucosaminoglycan synthesis. Supplemented glucosamine stimulates synthesis of cartilage glyscosaminoglycans and proteoglycans in a dose responsive manner.

Proteoglycan biosynthesis is enhanced by two mechanisms: the availability of substrate for the macormolecules and a stimulating effect on the incorporation of other essential substrates. Incorporation of supplemented glucosamine into newly synthesized glycosaminoglycans has been confirmed. Specific stimulation of hyaluronan synthesis has also been demonstrated. Studies have shown selective incorporation of glucosamine into articular cartilage, and specifically into newly synthesized proteoglycans, and have shown that glucosamine reverses the damage to cartilage produced in experimental models of osteoarthritis.

Similarly, electron microscopic examination of cartilage samples taken before and after treatment of human osteoarthritis with glucosamine or a placebo demostrated reversal of cartilage degradation in people receiving glucosamine and not in those receiving the placebo. Glucosamine also counteracted metabolic ana morphological damage to cartilage-producing cells caused by intra-articular steriod injection.

Further studies have shown that glucosamine inhibits production of free radicals such as superoxide and lysosomal enzymes. Glucosamine also inhibits nitric oxide production, proteoglycan loss, gelatinase and collagenase activity in equine cartilage exposed to inflammatory agents such as lipopolysaccharide and recombinant interleukin 1.

These studies confirm glucosamine's anti-inflammatory activity, produced without inhibiting the synthesis of prostaglandins, a major side effect of nonsteroidal anti-inflammatory drugs such as phenylbutazone. The anti-inflammatory activity of glucosamine is achieved through a prostaglandin independent mechanism, which not only contributes to cartilage preservation but also provides protection against the metabolic impairment induced by nonsteroidal anti-inflammatory drugs. Therefore, supplemented glucosamine both decreases inflammation and joint pain, aids in the repair of joint cartilage and is highly beneficial in the treatment and/or prevention of osteoarthritis.

Six randomized trials involving oral glucosamine in the treatment of human arthrosis/osteoarthritis have been reported. In each case the oral dose of glucosamine was 1.5 grams per day, or 1,000 milligrams per 100 pounds. In four trials glucosamine was compared with a placebo and all showed statistical superiority of glucosamine. Two trials compared glucosamine to ibuprofen (a nonsteroidal anti-inflammatory drug) in the treatment of human knee osteoarthritis. The first reported ibuprofen to produce superior symptomatic improvement after two weeks treatment, but glucosamine to result in better clinical features after eight weeks of treatment. the second reported a similar difference in response at two weeks, but from three weeks onwards there was no significant differerence in response between ibuprofen and glucosamine. However, the adverse side effects were significantly lower with glucosamine than ibuprofen. Other authors have also noted that the beneficial effects of glucosamine take an average of two to three weeks before clinical improvement is reported. Glucosamine has also proved superior to phenylbutazone in the management of back pain and to a placebo in the treatment of spinal osteoarthritis.

Many joint supplements contain a variety of substances. Only two, chondroitin sulphate and glucosamine, have been subjected to intense scientific testing. The actions, interactions, efficacy and toxicity of the remainder of oral joint supplements remain largely unknown.

It appears that chondroitin sulphate is not absorbed following oral administration but that low molecular weight desulphated degradation products of the disaccharide polymer probably are absorbed. Unfortunately, the existence of a polymer chain and the presence of sulphate groups are necessary for the biological activity of chondroitin sulphate. Positive clinical responses to oral supplements with chondroitin sulphate may be explained either by biological activity of its low molecular weight degradation products such as individual glycosamine units or from the activity of other substances such as glucosamine.

Glucosamine is a small molecule. It has a pKa of 6.91 which is very favorable for absorption from the small intestine and for crossing biological barriers in the body. It is not protein bound in plasma and therefore interactions with other drugs are unlikely. Glucosamine is also devoid of antigenic (allergic) properties. Following oral administration of glucosamine hydrochloride, like that in Top Form Joint Supplement, or glucosamine sulphate there is gastric dissociation of the salts liberating non-ionized glucosamine. The hydrochloride salt yields a greater amount of active glucosamine than the sulphate (Top Form Joint Supplement is pure glucosamine hydrochloride). The ability of glucosamine to exists in a non-ionized form contributes directly to its bioavailability.

Almost complete bioavailability of glucosamine has been demonstrated following oral administration. Gastrointestinal tract absorption without any metabolic breakdown of the molecule has been quantified in man at 90%. All authors have also demonstrated affinity for articular cartilage which has been quantified as 30%.

Toxicity with oral glucosamine in man is practically absent which makes it suitable for long-term treatment regimes. In placebo controlled studies the incidence of reported adverse effects with glucosamine has not differed from administration of the placebo. Safety in conjunction with other medications has also been documented in man. In all species studies, the literature indicates that glucosamine is efficiently absorbed following oral administration. It is safe, has affinity for articular cartilage and is a physiologic substrate for and stimulator of glycosaminoglycan synthesis. Glucosamine has anti-inflammatory properties and currently is the oral supplement of choice for the management of osteoarthritis in man.