Arthritis

Note: The following abstracts are written in extremely technical language and include technical research and case studies. References are provided. For 'user-friendly' informative reading, check out the health topics presented by Dr. Martin and Dr. Davenport. Feel free to contact us for more information or if you have any questions.

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.

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

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.

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

Alteration of cartilage metabolism by cells from osteoarthritic bone.

OBJECTIVE: To determine whether bone cells alter cartilage metabolism.

METHODS: Bone cell cultures were established using explants obtained from the hip and knee joints of 9 patients with osteoarthritis (OA) and 6 subjects without arthritis (nonarthritic [NA]). NA human cartilage biopsy samples were incubated in the presence or absence of bone-derived cells, and the effects on glycosaminoglycan (GAG) release from cartilage were measured.

RESULTS: Bone cell cultures secreted osteocalcin (OC) and did not contain cells expressing leukocyte common antigen. None of the 8 cultures established from NA bone, compared with 17 of 32 from OA bone, significantly altered GAG release from cartilage (P = 0.006). In knees with medial joint damage, 38% of the cultures derived from the medial side of the joint increased GAG release from cartilage. In contrast, 77% of the cultures derived from the lateral side of the joint had an effect on GAG, with 38% increasing and 38% decreasing GAG release. Seven cytokines were measured in OA bone cell supernatants. No significant difference was apparent in the concentration of any one cytokine when supernatants were compared according to their effects on GAG release.

CONCLUSION: Bone cells from OA patients can influence cartilage metabolism. This might explain why increased subchondral bone activity can predict cartilage loss.

Westacott-CI; Webb-GR; Warnock-MG; Sims-JV; Elson-CJ
Arthritis-Rheum. 1997 Jul; 40(7): 1282-91

Gd-DTPA2- as a measure of cartilage degradation [published erratum appears in Magn Reson Med 1996 Dec;36(6):964]

Glycosaminoglycans (GAGs) are the main source of tissue fixed charge density (FCD) in cartilage, and are lost early in arthritic diseases. We tested the hypothesis that, like Na+, the charged contrast agent Gd-DTPA2- (and hence proton T1) could be used to measure tissue FCD and hence GAG concentration. NMR spectroscopy studies of cartilage explants demonstrated that there was a strong correlation (r > 0.96) between proton T1 in the presence of Gd-DTPA2- and tissue sodium and GAG concentrations. An ideal one-compartment electrochemical (Donnan) equilibrium model was examined as a means of quantifying FCD from Gd-DTPA2- concentration, yielding a value 50% less but linearly correlated with the validated method of quantifying FCD from Na+. These data could be used as the basis of an empirical model with which to quantify FCD from Gd-DTPA2- concentration, or a more sophisticated physical model could be developed. Spatial distributions of FCD were easily observed in T1-weighted MRI studies of trypsin and interleukin-1 induced cartilage degradation, with good histological correlation. Therefore, equilibration of the tissue in Gd-DTPA2- gives us the opportunity to directly image (through T1 weighting) the concentration of GAG, a major and critically important macromolecule in cartilage. Pilot clinical studies demonstrated Gd-DTPA2- penetration into cartilage, suggesting that this technique is clinically feasible.

Bashir-A; Gray-ML; Burstein-D
Magn-Reson-Med. 1996 Nov; 36(5): 665-73

Galactosaminoglycuronglycan sulfate in erosive osteoarthritis of the hands: early diagnosis, early treatment.

This study examined the effect of an oral chondroprotective drug, galactosaminoglycuronglycan sulfate (GAGs), on the evolution of erosive osteoarthritis of the hands (EOA). Twenty-four patients affected with EOA of the hands were evaluated. The patients had painful, frank arthritis of DIP and PIP joints; X-rays reduced joint space; X-rays central joint erosions; positive joint scintiscan, in absence of other inflammatory and erosive arthropathies. Twelve patients were treated with a chondroprotective drug, GAGs 800 mg/ die; twelve patients were the control group. The results at two years documented that the GAGs treatment influenced certainly joint pain and doubtfully bone scintiscan in EOA.

Rovetta-G; Monteforte-P
Int-J-Tissue-React. 1996; 18(1): 43-6

Therapeutic trials in digital osteoarthritis. A critical review.

Although common, hand osteoarthritis is controversial and rarely used as a model for clinical trials in osteoarthritis. We found only 13 therapeutic trials conducted in digital or trapeziometacarpal osteoarthritis between 1983 and 1994. Eleven of these trials were published. Seven were on nonsteroidal antiinflammatory drugs given either per os (two trials, meclofenamate and ibuprofen) or percutaneously (one trial each on etofenamate, ibuprofen, and ketoprofen gel, and two trials on niflumic acid gel), three were on symptomatic slow-acting drugs (glycosaminoglycanes in two trials and chondroitin sulfate in one), and three were on miscellaneous agents (the muscle relaxant idrocilamide, as a gel; the antisubstance P agent capsaicin, also as a gel; and a spa treatment). We have reviewed the methodology and findings of these trials with the goal of determining the optimal approach to realize better standardized trials in the next future for identifying symptomatic slow-acting drugs and/or "chondroprotective" agents with beneficial effects in digital osteoarthritis.

Treves-R; Maheu-E; Dreiser-RL
Rev-Rhum-Engl-Ed. 1995 Jun; 62(6 Suppl 1): 33S-41S

Glycosaminoglycan polysulfuric acid (GAGPS) in osteoarthritis of the knee.

We studied the efficacy and tolerability of glycosaminoglycan polysulfuric acid (GAGPS) in 80 patients with osteoarthritis (OA) of the knee. Patients received two series of five intra-articular injections, at 1-week intervals, of 25 mg (0.5 ml) GAGPS into the knee in a double-blind, parallel, randomized, placebo-controlled trial. There was an immediate decrease in pain after the injections of 43% with GAGPS and 33% with placebo (P = 0.047) (Jezek pain index). Pain relief of GAGPS vs placebo was not different at other intervals (10, 14, 22, 26 weeks after start of treatment). At 6 weeks the Lequesne index decreased 20% after GAGPS and 9% after placebo (P = 0.17). At 10 weeks the Lequesne index decreased 24% after GAGPS and 13% after placebo (P = 0.20). The decrease in Lequesne index at 14 weeks was 31% after GAGPS and 15% after placebo (P = 0.06). The other measured parameters tended to be more favorably influenced by GAGPS than placebo. GAGPS was well tolerated, with associated mild adverse reactions in 8% of cases. GAGPS may have a role as a symptomatic slow acting drug for OA. Further study appears appropriate.

Pavelka-K Jr; Sedlackova-M; Gatterova-J; Becvar-R; Pavelka-K Sr
Osteoarthritis-Cartilage. 1995 Mar; 3(1): 15-23

Polysulfated glycosaminoglycan in the treatment of osteoarthritis.

Todhunter-RJ; Lust-G
J-Am-Vet-Med-Assoc. 1994 Apr 15; 204(8): 1245-51

Glycosaminoglycan chondroprotection: pharmacological vistas.

Chondroprotection is a somewhat new field in the therapy of osteoarthritis, which is designed to improve cartilage repair as well as enhance joint remodeling. It clearly results from both laboratory models as well as from studies on human osteoarthritis, that cartilage contains biological resources to meet the repair of degenerative injuries and inflammation. Interestingly, sulfated glycosaminoglycans from matrix inhibit leukocyte protease and complement-mediated immunological reactions. By fractioning cartilage glycosaminoglycans from Selachus (Matrix), evidence has been obtained that a proper chondroitinsulfate sequence, which is able to inhibit elastase, may be released from cartilage proteoglycans by cleavage of the xyl-ser O-glycosidic bond. Since a number of sulfated glycosaminoglycans have a regulatory function in an array of tissues, attention is drawn to possible regulatory properties of selected sequences of matrix chondroitinsulfate, as far as chondroprotection is concerned.

Paroli-E
Int-J-Clin-Pharmacol-Res. 1993; 13 Suppl: 1-9



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