Roland W. Moskowitz
Objectives: To review the current status of collagen hydrolysate in the treatment of osteoarthritis and osteoporosis.
Methods: Review of past and current literature relative to collagen hydrolysate metabolism, and assessment of clinical investigations of therapeutic trials in osteoarthritis and osteoporosis.
Results: Hydrolyzed collagen products have long been used in pharmaceuticals and foods. These products are generally recognized as safe food products by regulatory agencies. Pharmaceutical-grade collagen hydrolysate (PCH) is obtained by hydrolysis of pharmaceutical gelatin. Clinical studies suggest that the ingestion of PCH daily reduces pain in patients with osteoarthritis of the knee or hip, blood concentration of hydroxyproline is increased.
Clinical use is associated with minimal adverse effects, mainly gastrointestinal, characterized by fullness or unpleasant taste. I n a multicenter, randomized, double-blind, placebo-controlled trial performed in clinics in the United States, United Kingdom, and Germany.
Results showed no statistically significant differences for the total study group (all sites) for differences of mean pain score for pain. There was, however, a significant treatment advantage of PCH over placebo in German sites. In addition, increased efficacy for PCH as compared to placebo was observed in the overall study population amongst patients with more severe symptomatology at study onset. Preferential accumulation of 14C-labeled gelatin hydrolysate in cartilage as compared with administration of 14C-labeled proline has been reported. This preferential uptake by cartilage suggests that PCH may have a salutary effect on cartilage metabolism. Given the important role for collagen in bone structure, the effect of PCH on bone metabolism in osteoporotic persons has been evaluated. Studies of the effects of calcitonin with and without a collagen hydrolysate rich diet suggested that calcitonin plus PCH had a greater effect in inhibiting bone collagen breakdown than calcitonin alone, as characterized by a fall in levels of urinary pyridinoline cross-links. PCH appeared to have an additive effect relative to use of calcitonin alone.
Conclusions: Collagen hydrolysate is of interest as a therapeutic agent of potential utility in the treatment of osteoarthritis and osteoporosis. Its high level of safety makes it attractive as an agent for long term use in these chronic disorders. INDEX WORDS: Osteoarthritis osteoporosis collagen hydrolysate arthritis therapy cartilage & bone. ROLAND W. MOSKOWITZ Improved knowledge about disease origins, pathophysiology, and clinical presentations has led to significant advances in the management of both osteoarthritis (OA) and osteoporosis, two of the most common musculoskeletal disorders. Advances in the treatment of OA include newer, safer medicines targeted toward symptomatic relief such as COX-2 selective inhibitors (1,2) and intra-articular hyaluronans (3-7).
Further advances appear to be in the offing, with the development of medications directed toward disease modification, providing opportunity for disease retardation, stabilization, or reversal of structural changes. Tissue engineering, with opportunities for utilization of cells and matrix for tissue regeneration, adds additional excitement with the potential for comprehensive treatment of patients with joint degeneration. Similarly, a series of newly introduced medications provide opportunity for effective management of osteoporosis, with agents capable of both prevention and repair. Medications that include estrogenic hormone replacement, bisphos-phonates, calcitonin, selective estrogen receptor agonists, fluorides, and parathormone derivatives provide opportunity for specific disease modification, when used in association with exercise, calcium, and vitamin D intake. Unfortunately, in both OA and osteoporosis, therapeutic responses are limited in many patients despite the availability of new agents and modalities, or by toxicity or intolerance reactions in individual patients. Accordingly, even though significant gains have been made in the management of OA and osteoporosis, there remains significant room for development of medications that provide even greater symptomatic relief with less overall toxicity, as well as the formulation of agents capable of disease modification with minimal risks.
Over the past several decades, interest has expanded in me role of nutritional supplements Nutra-ceuticals) as both symptom-relieving agents and agents that may have a specific effect on disease pathophysiology and pathologic structural changes. Certain of these agents, such as glucosamine and chondroitin sulfate, have become extremely popular as health food supplements purported to be efficacious in the treatment of OA (8-14).
A number of short-term studies with these agents suggest that they have efficacy equal to that of nonsteroidal anti-inflammatory agents in the symptomatic management of OA. Similarly, clinical studies have suggested a role for collagen hydrolysate in the management of OA, based on the postulate that hydrolyzed collagen with its abundant amino acids plays a role in cartilage matrix synthesis (15-19). Gelatine products, which have been used as foods for a number of centuries, are attractive with respect to safety and overall lack of toxicity (20-22). Relief of OA pain in the knee or hip was noted in a study of patients receiving collagen hydrolysate daily over a 2-month period (15). Because collagen hydrolysate has not been shown to have a direct analgesic or anti-inflammatory effect, a direct effect on joint tissues has been hypothesized. Collagen (gelatine) also has been marketed as a supplement for the maintenance of normal bone integrity and as an agent in the treatment of brittle nails and abnormalities in scalp hair. Collagen has been used as a food since at least early medieval times.
The first known description of the beneficial effects of gelatin ingestion in humans is from 1175, when St Hildegard wrote that eating gelatin improved joint conditions by reducing pain. The first commercial manufacture of gelatin was in Holland around 1685. Today, US commercial production of gelatin exceeds 75 million pounds per year, and worldwide production exceeds 250,000 metric tons, of which more than 60% is consumed in various kinds of products by humans.
Hydrolyzed collagen products have long been used in Pharmaceuticals and foods in the United States and Europe. Gelatin and a broad range of hydrolyzed gelatin products of varying molecular weights are widely ingested as foods in the United States. All of these products have either been affirmed as generally recognized as safe (GRAS) food products or have been proposed as GRAS by the Food and Drug Administration (FDA) Center for Food Safety and Nutrition.