Glucosamine Sulfate Glucosamine sulphate for the management of arthrosis; a controlled clinical investigation.
Crolle, G. and D'Este, E. Curr.Med.Res.Opin. 7 (2):104-109, 1980.
A new preparation of pure glucosamine sulphate, in injectable and oral form, was investigated in a controlled clinical trial in patients with osteoarthrosis. Two groups of 15 in-patients received either 400 mg glucosamine sulphate daily (12 by the intramuscular and 3 by the intra-articular route) for 7 days, followed by 2 weeks at 1.5 g daily or oral glucosamine sulphate in 3 divided doses, or an intramuscular injection daily of a piperazine/ chlorbutanol combination for 7 days, followed by oral placebo during the following 2 weeks. Semi-quantitative scoring of pain at rest and during active and passive movements, of restricted function and, where possible, of walking time over 20 meters, were taken as therapeutic activity indices and tested before and after 1 and 3 weeks of treatment. Patients were positively questioned daily for possible intolerance symptoms. Laboratory tests were recorded before and after treatment. With both initial parenteral treatments, each symptom significantly improved, with a trend for faster and greater recovery with glucosamine, mainly in restricted function. During the maintenance period, a further significant improvement was recorded in the group receiving glucosamine, whereas with placebo the symptom scores rose to almost the pre-treatment levels. A similar pattern was shown in the measurement of walking speed. Clinical and biological tolerance were excellent with both treatments. No drug-related complaints were recorded, nor signs of interference in other illnesses or interactions with other drug treatments. It is suggested that injectable and/or oral treatment with pure glucosamine sulphate should be considered for the basic therapy of primary or secondary osteoarthrosis, mainly because it restores articular function to a certain extent.
Glucosamine sulphate: a controlled clinical investigation in arthrosis.
D'Ambrosio, E., Casa, B., Bompani, R., Scali, G., and Scali, M. Pharmatherapeutica. 2 (8):504-508, 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 of secondary degenerative osteoarthrosis disorders.
Therapeutic activity of oral glucosamine sulfate in osteoarthrosis: a placebo-controlled double-blind investigation.
Drovanti, A., Bignamini, A.A., and Rovati, A.L. Clin.Ther. 3(4):260-272, 1980.
Eighty inpatients with established osteoarthrosis received either 1.5 gm of glucosamine sulfate or placebo daily, in three divided oral dosed, for 30 days. Articular pain, joint tenderness and swelling, and restriction of active and passive movements were scored at one-week intervals, as were possible side reactions. Hematologic analysis urine analysis, and occult blood in feces were recorded before and after treatment. Samples of articular cartilage from two patients of each patients of each group and from one healthy subject were submitted to scanning electron microscopy after the end of treatment. All symptoms decreased in both groups. The patients treated with glucosamine sulfate experienced a reduction in overall symptoms that was almost twice as large (73% vs 41%) and twice as fast (time to reduce symptoms by 50%: 20 days vs. 36 days) as those who had placebo. The improvement of autonomous mobility was relatively less, compared to improvement in the other symptom, for patients with placebo; with glucosamine sulfate, on the contrary, the improvement was as great and as fast as that of those other symptoms. Thus a direct action of glucosamine sulfate on the cartilage is hypothesized.
This hypothesis is supported by the findings of electron microscopy. The patients who had placebo showed a typical picture of established osteoarthrosis. Those who has glucosamine sulfate showed a picture more similar to healthy cartilage. It is concluded that glucosamine sulfate tends to rebuild the damaged cartilage, this restoring articular function in most chronic arthrosic patients.
The neglect of glucosamine as a treatment for osteoarthritis-a personal perspective
McCarty, M.F. Med.Hypotheses. 42(5):323-327, 1994.
Osteoarthritis results from progressive cartabolic loss of cartilage proteoglycans, owing to an imbalance between synthesis and degradation. Standard drug therapy is only 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 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 ignores 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.
Double-blind clinical evaluation of oral glucosamine sulphate in the basic treatment of osteoarthritis.
Pujalte, J.M., Llavore, E.P., and Ylescupidez, F.R. Curr.Med.Res.Opin. 7(2):110-114, 1980.
Notes: 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 scores 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.
Pharmacokinetics of glucosamine in man.
Setnikar, I., Palumbo, R., Canali, S., and Zanolo, G. Arneimittelforschung. 43(10):1109-1113, 1993.
The pharmacokinetics of glucosamine sulfate (CAS 29031-19-4) was investigated in 6 healthy male volunteers (2 per administration route) using 14C uniformly labeled glucosamine sulfate and administering it in single dose by intravenous (i.v.), intramuscular (i.m.) or oral route. The results show that after i.v. administration the radioactivity due to glucosamine appears in plasma and is rapidly eliminated, with an initial t1/2 of 0.28 h. 1-2 h after administration the radioactivity due to glucosamine disappears almost completely and is replaced by a radioactivity origination from plasma proteins, in which glucosamine or its metabolites are incorporated. This radioactivity reaches a peak after 8-10h and then declines with a t1/2 of 70h. About 28% of the administered radioactivity is recovered in the urine of 120 h following the administration and less than 1% is recovered in the feces. After i.m. administration similar pharmacokinetic patterns are observed. After oral administration a proportion close to 90% of glucosamine sulfate is absorbed. Free glucosamine is not detectable in plasma. The radioactivity incorporated in the plasma proteins follows pharmacokinetic patterns which are similar to those after i.v. or i.m. administration, but its concentration is plasma is about 5 times smaller than that after parenteral administration. The AUC after oral administration is 26% of that after i.v., or i.m. administration. The smaller plasma levels of radioactivity after oral administration are probably due to a first pass effect in the liver which metabolizes a notable proportion of glucosamine into smaller molecules and ultimately to CO2, water and urea.
Double-blind clinical evaluation of the relative efficacy of ibuprofen and glucosamine sulphate in the management of osteoarthrosis of the knee in out-patients.
Lopes Vaz, A. Curr.Med.Res.opin. 8(3):145-149, 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 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.
The efficacy and safety of glucosamine sulfate in the treatment of gonarthritis.
Giordano N, Nardi P, Senesi M, Palumbo F, Battisti E, Gonnelli S, Franci B, CampagnaMS, Gennari C. Clin.Ter.147(3):99-105, 1996.
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 mild to moderate and did not require discontinuation of the drug.
Glucosamine for wound healing.
McCarty, M.F. Med.Hypotheses. 47(4):273-275, 1996.
The rapid production of hyaluronic acid by fibroblasts in the early stages of wound healing may be of crucial importance as hyaluronic acid stimulates the migration and mitosis of mesenchymal and epithelial cells. Increased levels of hyaluronic acid, as observed during fetal wound healing or as achieved by the topical application of hyaluronic acid during wound dressing, are associated with brisker healing and reduced scarring. Glucosamine availability appears to be rate-limiting for hyaluronic acid synthesis. Thus the administration of adequate amounts of glucosamine by mouth during the first few days after surgery or trauma can be expected to enhance hyaluronic acid production in the wound, promoting swifter healing and possibly diminishing complications related to scarring.
Efficacy and safety of intramuscular glucosamine sulfate in osteoarthritis of the knee. A randomised, placebo-controlled, double- blind study.
Reichelt, A., Forster, K.K., Fischer, M., Rovati, L.C., and Setnikar, I. Arzneimittelforschung. 44(1):75-80, 1994.
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, randomised, 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 judgment 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)
Clinical research in osteoarthritis: design and results of short-term and long-term trials with disease-modifying drugs.
Rovati, L.C. Int.J.Tissue React. 14(5):243-251, 1992.
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.
Antireactive properties of "chondroprotective" drugs.
Setnikar, I. Int.J.Tissue React. 14(5):253-261, 1992.
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 antiinflammatory 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 antiinflammatory 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.
Oral glucosamine sulphate in the management of arthrosis: report on a multi-centre open investigation in Portugal.
Tapadinhas, M.J., Rivera, I.C., and Bignamini, A.A. Pharmatherapeutica. 3(3):157-168, 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 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.