Pharmatherapeutica, 2(8):504-8 1981

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.

Clin Ther, 3(5):336-43 1981

Fifty-four outpatients with gonarthrosis participated in a double-blind clinical test with the aim of evaluating the efficacy and tolerance of intra-articular glucosamine in comparison with a 0.9% NaCl placebo. Each patient had one intra-articular injection per week for five consecutive weeks. Pain, active and passive mobility of the joint, swelling, and generalized and local intolerance symptoms were recorded before beginning the treatment, and four weeks after the last injection. glucosamine reduced pain to a significantly greater extent than did placebo, and resulted in significantly more pain-free patients. The angle of joint flexion substantially increased after glucosamine treatment. Active mobility increased with both treatments, with a more favorable trend after glucosamine administration. Knee swelling did not decrease significantly after glucosamine, whereas it worsened (although no significantly) after placebo. There were no local or general intolerance symptoms during and after treatment. Glucosamine administration was able to accelerate the recovery of arthrosic patients, with no resulting side effects, and to partially restore articular function. In addition, the clinical recovery did not fade after treatment ended, but lasted for the following month, at least. These features are a definite improvement over antirheumatic drugs, the major drawbacks of which are action of short duration and side effects. Glucosamine therapy therefore deserves a selected place in the management of osteoarthrosis.

Curr Med Res Opin, 7(2):110-14 1980

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 glucosaminene 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.

Pharmatherapeutica, 7(2):157-68 1982

An open study was carried out by 252 doctors throughout Portugal to assess the effectiveness and tolerability of oral glucosamine sulphate in the treatment of arthrosis. Patients received 1.5 g daily in 3 divided doses over a mean period of 50 +/- 14 days. The results from 1208 patients were analyzed and showed that the symptoms of pain at rest, on standing and on exercise and limited active and passive movements improved steadily through the treatment period. The improvement obtained lasted for a period of 6 to 12 weeks after the end of treatment. Objective therapeutic efficacy was rated by the doctors as 'good' in 59% of patients, and 'sufficient' in a further 36%. These results were significantly better than those obtained with previous treatments (except for injectable glucosamine) in the same patients. Sex, age, localization of arthrosis, concomitant illnesses or concomitant treatments did not influence the frequency of responders to treatment. Oral glucosamine was fully tolerated by 86% of patients, a significantly larger proportion than that reported with other previous treatments and approached only by injectable glucosamine. The onset of possible side-effects was significantly related to pre-existing gastro-intestinal disorders and related treatments, and to concomitant diuretic treatment.

Curr Med Res Opin, 8(3):145-9 1982

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 favour 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.

Arzneimittelforschung, 48(5):469-74 1998 May

A double-blind therapeutic investigation was performed on 178 Chinese patients suffering from osteoarthritis of the knee randomized into two groups, one treated for 4 weeks with glucosamine sulfate (GS, CAS 29031-19-4, Viartril-S) at the daily dose of 1,500 mg and the other with ibuprofen (IBU, CAS 15687-27-1) at the daily dose of 1,200 mg. Knee pain at rest, at movement and at pressure, knee swelling, improvement and therapeutic utility as well as adverse events and drop-outs were recorded after 2 and 4 weeks of treatment. The variables were recorded also after 2 weeks of treatment discontinuation in order to appreciate the remnant therapeutic effect. Both GS and IBU significantly reduced the symptoms of osteoarthritis with the trend of GS to be more effective. After 2 weeks of drug discontinuation there was a remnant therapeutic effect in both groups, with the trend to be more pronounced in the GS group. GS was significantly better tolerated than IBU, as shown by the adverse drug reactions (6% in the patients of the GS group and 16% in the IBU group--p = 0.02) and by the drug-related drop-outs (0% of the patients in the GS group and 10% in the IBU group--p = 0.0017). The better tolerability of GS is explained by its mode of action, because GS specifically curbs the pathogenic mechanisms of osteoarthritis and does not inhibit the cyclo-oxygenases as the non-steroidal anti-inflammatory drugs (NSAIDs) do, with the consequent anti-inflammatory analgesic activities but also with the several adverse reactions due to this not targeted effect. The present study confirms that GS is a selective drug for osteoarthritis, as effective on the symptoms of the disease as NSAIDs but significantly better tolerated. For these properties GS seems particularly indicated in the long-term treatments needed in osteoarthritis.

Arzneimittelforschung, 48(5):729-35 1986 Apr

The pharmacokinetics, organ distribution, metabolism and excretion of glucosamine were studied in the dog giving uniformly labelled [14C]-glucosamine (sulfate), i.v. or orally, in single doses. Immediately after i.v. administration, the radioactivity in plasma is due to glucosamine, and freely diffuses into organs and tissues. This radioactivity disappears quickly from plasma (initial t1/2 = 13 min, terminal t1/2 = 118 min). After 30-60 min the radioactivity in plasma is no longer due to glucosamine, but is incorporated into alpha- and beta-globulins. The protein-incorporated radioactivity is found already 20-30 min after i.v. administration, reaches a peak after 8 h and then slowly disappears, with a t1/2 = 2.9 days. Of the administered radioactivity, more than 34% is excreted in the urine, mainly as glucosamine, and 1.7% is excreted in the feces. Radioactivity is excreted also as [14C]-CO2 in the expired air. The radioactivity, after i.v. administration, diffuses rapidly from blood into the body. Some organs show an active uptake of radioactivity, e.g. the liver and the kidney. Other tissues, such as the articular cartilage, also have an active uptake. In most other organs the radioactivity found can be explained by passive diffusion processes from plasma. After oral administration of a single dose of [14C]-glucosamine the radioactivity is quickly and almost completely absorbed from the gastrointestinal tract. The pattern of disappearance, metabolic transformation, tissue distribution and excretion of the radioactivity are consistent with those found after i.v. administration.

Arch Int Pharmacodyn Ther, 48(5):4-10 1977 Mar

The in vitro inhibition of the glucosamine synthetase activity of rat gastric mucosal homogenates by sodium salicylate and phenylbutazone has been previously reported and has been adduced as a possible mechanism for the ulcerogenic effect of these drugs. This inhibition has been confirmed in human gastric and colonic mucosal homogenates and it is also shown by acetylsalicylic acid and by hydrocortisone hemisuccinate. However, paracetamol and gentamicin, neither of which is known to be ulcerogenic, also inhibited the enzyme to a similar degree to the ulcergenic drugs. This refutes glucosamine synthetase inhibition as the mechanism of the ulcerogenic action of anti-inflammatory drugs.

Arch Virol, 52(1-2):169-73 1976

Intraperitoneal treatments with D-glucosamine, an inhibitor of the glycosylation of the viral envelope, decreased the growth rate of tumors induced in quails or in chicks by Rous sarcoma virus and increased the survival of mice inoculated with human influenza virus.

Med Hypotheses, 48(3):245-51 1997 Mar

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.

Mil Med 1999 Feb;164(2):85-91

OBJECTIVE: A 16-week randomized, double-blind, placebo-controlled crossover trial of a combination of glucosamine HCl (1,500 mg/day), chondroitin sulfate (1,200 mg/day), and manganese ascorbate (228 mg/day) in degenerative joint disease (DJD) of the knee or low back was conducted. METHODS: Thirty-four males from the U.S. Navy diving and special warfare community with chronic pain and radiographic DJD of the knee or low back were randomized. A summary disease score incorporated results of pain and functional questionnaires, physical examination scores, and running times. Changes were presented as a percentage of the patient's average score. RESULTS: Knee osteoarthritis symptoms were relieved as demonstrated by the summary disease score (-16.3%; p = 0.05), patient assessment of treatment effect (p = 0.02), visual analog scale for pain recorded at clinic visits (-26.6%; p = 0.05) and in a diary (-28.6%; p = 0.02), and physical examination score (-43.3%; p = 0.01). Running times did not change. The study neither demonstrated, nor excluded, a benefit for spinal DJD. Side effect frequency was similar to that at baseline. There were no hematologic effects. CONCLUSIONS: The combination therapy relieves symptoms of knee osteoarthritis. A larger data set is needed to determine the value of this therapy for spinal DJD. Short-term combination therapy appears safe in this setting.

Cranio 1998 Oct;16(4):230-5

The signs and symptoms of osteoarthritis are common complaints seen in patients suffering with chronic temporomandibular disorders (TMD), specifically, internal derangements with a diagnosis of osteoarthritis. With or without the complaints of pain and swelling, joint noises are bothersome and annoying to both the patient and at times, to those seated close to the patient during mealtime. In fact, many patients are driven to seek care by family members because of his or her TMJ noises. For years in veterinarian medicine, glucosamine and chondroitin sulfates have been used to treat symptoms of osteoarthritis. Recently, the use of these two supplements has been recommended for human beings as well. Reports of decreased joint noises, pain and swelling after the administration of therapeutic doses of these supplements have sparked an interest in their possible use in the treatment of osteoarthritis.