Glucosamine Research

Note: The following abstracts are written extremely technically oriented and includes technical research and case studies. References are provided. For 'user-friendly' informative reading, check out the topical discussions presented by Dr. Martin and Dr. Davenport.  Feel free to contact us for more information or any questions you may have!

Double-blind clinical evaluation of the relative efficacy of ibuprofen and glucosamine sulphate in the management of osteoarthrosis of the knee in out-patients.

A double-blind trial was carried out in 40 out-patients with unilateral osteoarthrosis of the knee to compare the efficacy and tolerance of oral treatment with 1.5 g glucosamine sulphate or 1.2 g ibuprofen daily over a period of 8 weeks. Pain scores decreased faster during the first 2 weeks in the ibuprofen than in the glucosamine treatment group. Although the rate of decrease was slower, the reduction in pain scores was continued throughout the trial period in patients an glucosamine and the difference between the two groups turned significantly in favor of glucosamine at Week 8. No significant differences were observed in swelling or any of the other parameters monitored. Tolerance was satisfactory with both treatments, with only minor complaints being reported by 2 patients on glucosamine compared with 5 patients on ibuprofen.

Author: Lopes-Vaz-A
Curr-Med-Res-Opin. 1982; 8(3): 145-9

Conservative management of spinal osteoarthritis with glucosamine sulfate and chiropractic treatment.

OBJECTIVE: To evaluate the rationale behind the most commonly used treatments of osteoarthritis, including nonsteroidal anti-inflammatory drugs (NSAIDs), and to assess more effective conservative treatment options.

SUMMARY OF BACKGROUND DATA: This review includes a description of the pathophysiology and prevalence of osteoarthritis, joint physiology and NSAID treatment of osteoarthritis, as well as side effects on joints, the gastrointestinal tract, kidneys and livers. Several studies of conservative treatment, consisting of supplementation of glucosamine sulfate (which occurs naturally in the human body), exercise, and the use of chiropractic treatment for maintaining joint function and preventing further destruction, are reviewed.

DATA SOURCES: A computerized search of Medline using the key indexing terms osteoarthritis, degenerative joint disease, nonsteroidal anti-inflammatory drugs, glucosamine sulfate, chiropractic and manipulation.

RESULTS: Numerous studies wee obtained under each subheading and reviewed by category. Human and animal-model studies are described.

CONCLUSION: The rationales for using NSAIDs in the treatment of osteoarthritis is controversial and openly contested. Given the detrimental effects of NSAIDs on joints and other organs, their use should be discouraged and their classification as a first choice conservative treatment should be abolished. A truly effective and conservative approach to the treatment of osteoarthritis should include chiropractic manipulation, essential nutrient supplementation, exogenous administration of glucosamine sulfate and rehabilitative stretches and exercises to maintain joint function. Because there is no correlation between pain levels and the extent of degeneration detected by radiographic or physical examination, conservative treatment should be initiated and sustained based on functional, objective findings and not strictly on how the patient feels. The use of NSAIDs should be limited to the treatment of gross inflammation and analgesics should only be used in the short-term when absolutely necessary for pain palliation. The present conservative approach could lead not only to a better quality of life but also to the saving of health care dollars by reducing the iatrogenic morbidity and mortality associated with NSAID use.

Author: Gottlieb-MS
J-Manipulative-Physiol-Ther. 1997 Jul-Aug; 20(6): 400-14

The efficacy and safety of glucosamine sulfate in the treatment of gonarthritis

This study was performed to evaluate the therapeutic efficacy and tolerability of glucosamine sulfate in patients with gonarthritis. During the 12-month study period, the signs and symptoms of the disease were evaluated, as well as the dosage of the urinary pyridinoline. In this trial, we demonstrated that glucosamine sulfate has a chondroprotective activity, which was significant after the first 3 months of therapy. Moreover, this study showed that the side effects due to glucosamine sulfate were mild to moderate and did not require discontinuation of the drug.

Author: Giordano-N; Nardi-P; Senesi-M; Palumbo-F; Battisti-E; Gonnelli-S; Franci-B; Campagna-MS; Gennari-C
Clin-Ter. 1996 Mar; 147(3): 99-105

The neglect of glucosamine as a treatment for osteoarthritis--a personal perspective.

Osteoarthritis results from progressive catabolic loss of cartilage proteoglycans, owing to an imbalance between synthesis and degradation. Standard drug therapy is only of palliative benefit and may exacerbate loss of cartilage. Glucosamine is an intermediate in mucopolysaccharide synthesis, and its availability in cartilage tissue culture can be rate-limiting for proteoglycan production. A number of double-blind studies dating from the early 1980s demonstrate that oral glucosamine decreases pain and improves mobility in osteoarthritis, without side effects. Nevertheless, medical researchers and physicians in the US have totally ignored this rational and safe therapeutic strategy. By mechanisms that are still unclear, the natural methyl donor S-adenosylmethionine also promotes production of cartilage proteoglycans, and is therapeutically beneficial in osteoarthritis in well-tolerated oral doses. These and other safe nutritional measures supporting proteoglycan synthesis, may offer a practical means of preventing or postponing the onset of osteoarthritis in older people or athletes.

Author: McCarty-MF
Med-Hypotheses. 1994 May; 42(5): 323-7

Efficacy and safety of intramuscular glucosamine sulfate in osteoarthritis of the knee. A randomized, placebo-controlled, double-blind study.

Glucosamine sulfate (Dona, CAS 29031-19-4) is a drug used in the treatment of osteoarthritis. When orally given, it is more effective than placebo and at least as effective as non-steroidal anti-inflammatory drugs in relieving osteoarthritis symptoms. The aim of this multicentre, randomized, placebo-controlled, double-blind, parallel-group study was to assess the efficacy and safety of glucosamine sulfate intramuscularly given on the same parameters. 155 out-patients with knee osteoarthritis (Lequesne's criteria), radiological stage between I and III, Lequesne's severity index of at least 4 points and symptoms for at least 6 months, were treated with i.m. glucosamine sulfate (or placebo) 400 mg twice a week for 6 weeks. Clinic visits were performed at enrollment, after a 2-week baseline, at weekly intervals during treatment and 2 weeks after drug discontinuation. Responders to treatment were considered those patients with a reduction of at least 3 points in the Lequesne index, together with a positive overall judgement by the investigator. The Lequesne index was slightly over 10 points in average in both groups at the beginning of treatment. A significant decrease in the index was observed for glucosamine compared to placebo (3.3 vs. 2.0 points in average, respectively; p < 0.05, Student's t-test). The responder rate in the evaluable patients was 55% with glucosamine (n = 73) and only 33% (n = 69) with placebo (p = 0.012, Fisher's Exact Test). According to the intention-to-treat approach, considering also drop-outs, these proportions were 51% vs. 30% (p = 0.015).(ABSTRACT TRUNCATED AT 250 WORDS)

Author: Reichelt-A; Forster-KK; Fischer-M; Rovati-LC; Setnikar-I
Arzneimittelforschung. 1994 Jan; 44(1): 75-80

Antireactive properties of "chondroprotective" drugs.

The medicinal therapy of osteoarthritis is based on the use of analgesics, NSAIDs and corticosteroids to relieve pain and inflammation. In addition, "chondroprotective" agents (CPA) are used to stop the evolution of the disease. In this review the biochemical and pharmacological activities of some of the most widely used CPAs are described. All of these show more or less marked anti-inflammatory activities, which for some of them are the result of an inhibition of cyclo-oxygenase and of prostaglandin biosynthesis, in which case they should be more properly classified as mild NSAIDs. Only two of the CPAs reviewed, diacerein and D-glucosamine sulfate, elicit anti-inflammatory and antireactive effects without significant inhibition of the prostaglandin biosynthesis. These agents have also remarkable chondroprotective effects, and only these two agents should be classified as true CPAs. In particular glucosamine sulfate, which naturally occurs in the human body and is almost devoid of toxicity, is suitable for long-term therapeutic use. This, with its chondrometabolic, antireactive and antiarthritic properties, represents the pharmacological rationale for the use of glucosamine sulfate as a disease-modifying agent in osteoarthritis.

Author: Setnikar-I
Int-J-Tissue-React. 1992; 14(5): 253-61

Clinical research in osteoarthritis: design and results of short-term and long-term trials with disease-modifying drugs.

Putative disease-modifying drugs are usually clinically used in osteoarthritis with two main aims: not only stopping or reducing the cartilage degenerative process after a long-term treatment, but also controlling the symptoms of the disease within a few days or weeks, thus avoiding or diminishing the use of symptomatic medications. Due to the difficulties of implementing the first aim, the latter aim was more often investigated, even if most often with inadequate study design and insufficient numbers of patients. We have recently carried out three double-blind, controlled, parallel groups, randomized, 4-6 week trials of glucosamine sulphate versus placebo or the NSAID ibuprofen on a total of 606 gonarthrosic out-patients. Movement limitation and pain were scored according to the Lequesne index, and the efficacy goals were strictly pre-determined. Access to other medications was not allowed. Glucosamine was significantly more effective than placebo, while no difference was detected in comparison with the NSAID (p < 0.025 and p = 0.77, respectively: Fisher's two-tailed exact test). On the other hand, glucosamine was as well tolerated as placebo, while the percentage of patients suffering adverse drug reactions was higher in the ibuprofen group (37% vs 7%: p < 0.001). Long-term trials are in progress and several aspects are to be considered in their design: they must be double-blind, placebo-controlled, randomized, continued for a period of years and (most importantly) with the careful use of imaging and biochemical techniques capable of generating objective evaluation criteria.

Author: Rovati-LC
Int-J-Tissue-React. 1992; 14(5): 243-51

Glucosamine may retard atherogenesis by promoting endothelial production of heparan sulfate proteoglycans.

Heparan sulfate proteoglycans produced by vascular endothelium may function physiologically to restrain the migration, multiplication, and phenotypic transition of vascular smooth-muscle cells, and to maintain an anticoagulant luminal surface by bonding and activating antithrombin III. Thus, ample production of heparan sulfate proteoglycans may act to prevent atherosclerosis and its thrombotic complications. The ability of exogenous heparin to stimulate synthesis of heparan sulfate proteoglycans by vascular endothelium may be largely responsible for the positive outcomes of most controlled evaluations of low-dose heparin as a long-term therapy for coronary disease. Glucosamine, a biosynthetic precursor of mucopolysaccharides, can substantially enhance mucopolysaccharide production when added to cultured fibroblasts or chondrocytes; the clinical utility of oral glucosamine in osteoarthritis may reflect increased synthesis of cartilage proteoglycans. It is reasonable to speculate that exogenous glucosamine will likewise enhance heparan sulfate proteoglycans production by vascular endothelial cells, and, when administered orally in regimens comparable to those effective in osteoarthritis, will thereby act to retard atherogenesis.

Author: McCarty-MF
Med-Hypotheses. 1997 Mar; 48(3): 245-51

Pilot study of oral polymeric N-acetyl-D-glucosamine as a potential treatment for patients with osteoarthritis.

Glucosamine and its derivatives, such as glucosamine sulfate and N-acetyl-D-glucosamine (NAG), have been shown to be effective in the treatment of patients with osteoarthritis. Unfortunately, the half-life of glucosamine in the blood is relatively short; therefore, a sustained-release form of the compound would be highly desirable. The purpose of this pilot study was to determine whether the polymeric form of NAG (POLY-Nag) could provide a longer-lasting oral source of NAG. Ten healthy subjects each ingested 1 g/d of either NAG or POLY-Nag for 3 days. After a 4-day washout period, each subject was crossed over to receive the other compound for 3 days. Serum samples were collected and analyzed using high-performance liquid chromatography. Results show that orally ingested NAG and POLY-Nag are absorbed, resulting in increased serum levels of NAG, and POLY-Nag appears to be at least as effective as NAG. Serum levels of NAG had decreased by 48 hours after cessation of ingestion of NAG or POLY-Nag but were still above baseline levels. Increases in serum glucosamine levels indicate that NAG and POLY-Nag are converted to glucosamine in vivo. In conclusion, POLY-Nag may provide a source of serum glucosamine for treatment of patients with osteoarthritis. Longer and more rigorous pharmaco-kinetic and clinical studies need to be done.

Author: Talent-JM; Gracy-RW
Clin-Ther. 1996 Nov-Dec; 18(6): 1184-90

Changes in proteoglycans of human osteoarthritic cartilage maintained in explant culture: implications for understanding repair in osteoarthritis.

The maintenance of human osteoarthritic femoral head cartilage in long-term explant culture has been used to assess changes in newly synthesized and endogenous proteoglycans. Minced cartilage was radiolabeled with [3H]-leucine for 24 h. and the high density proteoglycans digested with tosyl-phenylalanine chloromethyl ketone-trypsin. Chondroitin-sulfate-rich peptides were separated from chondroitin-sulfate-poor peptides by DEAE-cellulose chromatography and hexuronic acid, protein, and galactosamine and glucosamine molar ratios determined. The incorporation of [3H]-leucine was highest in peptides enriched in chondroitin sulfate. when day 1 cultures were compared to those maintained for 20 days, several prominent changes were seen including, a reduction in the galactosamine to glucosamine ratio. Taken together with other data which showed a reduction in the hydrodynamic size of these proteoglycans with time in culture, these results showed that changes in the existing extracellular matrix pertinent to the osteoarthritic process can be assessed by maintaining cartilage in long-term organ-explant culture. A reduced hydrodynamic size of newly synthesized proteoglycans is consistent with a loss of chondroitin-sulfate and an increase in keratan sulfate in the high density proteoglycans.

Author: Malemud-CJ; Shuckett-R; Goldberg-VM
Scand-J-Rheumatol-Suppl. 1988; 77: 7-12

Antioxidant activity of synovial fluid, hyaluronic acid, and two subcomponents of hyaluronic acid. Synovial fluid scavenging effect is enhanced in rheumatoid arthritis patients.

To test the scavenging of reactive oxygen species (ROS), we added synovial fluids from patients with rheumatoid arthritis (RA) and osteoarthritis, as well as hyaluronic acid (HA) and its 2 subcomponents, D-glucuronic acid and N-acetyl-D-glucosamine, to 2 ROS-generating systems, activated neutrophils and xanthine-xanthine oxidase. Synovial fluid from RA patients, HA, and D-glucuronic acid markedly decreased the O2-, H2O2, OH., and chemiluminescence measured in both systems. HA and synovial fluid, which are known to be susceptible to degradation by excessive ROS in RA patients, also seem to play an active role in protecting articular tissues from oxidative damage.

Author: Sato-H; Takahashi-T; Ide-H; Fukushima-T; Tabata-M; Sekine-F; Kobayashi-K; Negishi-M; Niwa-Y
Arthritis-Rheum. 1988 Jan; 31(1): 63-71

Glucosamine sulphate: a controlled clinical investigation in arthrosis.

Efficacy and tolerance of a new preparation of pure glucosamine sulphate, in injectable and oral form, were investigated in 30 patients with osteoarthrosis. Two groups of in-patients with chronic degenerative articular disorders received daily for 7 days either 400 mg glucosamine sulphate or a piperazine/chlorbutanol combination by intravenous or intramuscular injection. During the 2 following weeks, the patients receiving glucosamine had oral glucosamine capsules (6 x 250 mg daily); the other group had placebo. Efficacy was tested by semi-quantitative scoring of pain at rest and during active and passive movements, as well as limitation of articular function, before and after 7 and 21 days of treatment. Patients were positively questioned daily for possible intolerance symptoms. Haematology, circulatory data and urine analysis were tested before and after treatment. During both initial parenteral treatments, each symptom significantly improved, but to a faster and greater extent in the group treated with glucosamine. During the maintenance period, a further improvement was recorded in the patients treated with glucosamine, whereas in those on placebo the symptom scores increased almost to the pre-treatment level. This was considered the major difference between basic therapy, such as with glucosamine, as purely symptomatic treatment. Clinical and biological tolerance were excellent with both treatments, and no definitely drug-related complaints were recorded. It is suggested that parenteral and/or oral treatment with pure glucosamine sulphate should be considered as basic therapy for the management of primary or secondary degenerative osteoarthrosis disorders.

Author: D'Ambrosio-E; Casa-B; Bompani-R; Scali-G; Scali-M
Pharmatherapeutica. 1981; 2(8): 504-8

Glucosamine: its importance for the metabolism of articular cartilage. 2. Studies on articular cartilage

In healthy individuals there exists a balance between cartilage proteoglycan synthesis and degradation. In arthrotic cartilage this metabolic balance is deteriorated in spite of a sometimes enhanced proteoglycan synthesis, since the catabolic rate exceeds the anabolic rate corresponding to the severity of the disease. The extracellular organic matrix of the cartilage is destroyed. With different experimental models it could be demonstrated, that the non steroidal anti-inflammatory drugs commonly used in the treatment of arthrosis inhibit the synthesis of mucopolysaccharides, intensify the already existing metabolic disorder, prevent a normalization of cartilage composition and thus impair the function of the cartilage. Glucosamine on the other hand increases in a dose-dependent way the ability of cartilage to synthesize both sulfated mucopolysaccharides and protein, thus restoring the catabolic-anabolic balance of the cartilage.

Author: Vidal-y-Plana-RR; Karzel-K
Fortschr-Med. 1980 Jun 5; 98(21): 801-6

Double-blind clinical evaluation of oral glucosamine sulphate in the basic treatment of osteoarthrosis.

The efficacy and tolerance of oral glucosamine sulphate were tested against placebo in a prospective double-blind trial in 20 out-patients with established osteoarthrosis. Two capsules of either glucosamine sulphate (250 mg) or placebo were administered 3-times daily over a period of 6 to 8 weeks. Articular pain, joint tenderness and restricted movement were semi-quantitatively scored 1 to 4 every 3 days, and individually averaged over the treatment period (overall composite score). Possible side-reactions were similarly scored upon positive questioning of the patients. Haematology, erythrocyte sedimentation rate, urine analysis and X-rays were recorded before and after treatment. Significant alleviation of symptoms was associated with the use of the active drug at the prescribed dose. Similarly, patients given glucosamine sulphate experienced earlier alleviation of symptoms compared with those who had placebo. The use of glucosamine sulphate also resulted in a significantly larger proportion of patients who experienced lessening or disappearance of symptoms within the trial period. No adverse reactions were reported by the patients treated with glucosamine, and no variation in laboratory tests was recorded.

Author: Pujalte-JM; Llavore-EP; Ylescupidez-FR
Curr-Med-Res-Opin. 1980; 7(2): 110-14

Metabolic activity of articular cartilage in osteoarthritis. An in vitro study.

Biochemical changes and in vitro rates of glycosaminoglycan synthesis were studied in thirty-seven samples of human articular cartilage from nineteen osteoarthritic and four normal control patients who were fifty to seventy-five years old. The samples were compared on the basis of histological grade of the arthritis, and subgroups based on the duration of disease, synovial pathological changes, joint studied, and sex were also compared. The osteoarthritic samples showed a progressive loss of glycosaminoglycans in the cartilage as the histological grade increased. In the early stages of the disease there was an increase in the chondroitin sulphate content as well as in the rate of glycosaminoglycan synthesis in several cases when the values for the osteoarthritic articular-cartilage samples were compared with those for the age-matched controls. In the late stages there was a progressive decrease in the rate of glycosaminoglycan synthesis and a relative decrease in chondroitin sulphate synthesis compared with keratan sulphate synthesis, and these decreases were highly correlated with the histological grade.

Author: Thompson-RC Jr; Oegema-TR Jr
J-Bone-Joint-Surg-Am. 1979 Apr; 61(3): 407-16

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