The following text and pictures area extracted/adapted from the excellent review article:
Glucosamine for Osteoarthritis: Biological Effects, Clinical Efficacy, and Safety on Glucose Metabolism
Juan Salazar, 1 Luis Bello, 1 Mervin Chávez, 1 Roberto Añez, 1 Joselyn Rojas,1,2 and Valmore Bermúdez 1
- Endocrine and Metabolic Diseases Research Center, Faculty of Medicine, University of Zulia, Maracaibo 4004, Venezuela
- Institute of Clinical Immunology, University of Los Andes, M´erida 5101, Venezuela
Correspondence should be addressed to Valmore Bermudez; firstname.lastname@example.org
Received 29 September 2013; Accepted 20 December 2013; Published 11 February 2014
Academic Editor: Jiri Vencovsky
Copyright © 2014 Juan Salazar et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
OA, also called osteoarthrosis, is a chronic arthropathy characterized by the degeneration and loss of articular cartilage, resulting in disruption of its mechanical properties and those of subchondral bone as well as modifications in the surrounding soft tissue. Although this process can develop in all osteoarticular structures, the knee remains the most accessibly assessed and the one with the most specific evaluation criteria.
Currently recognized pathophysiologic mechanisms involve not only articular lesion and degeneration but also a coexisting chronic inflammatory process which favors the progressive loss of hyaline cartilage through numerous molecular mediators. Furthermore, chondral structures may not be the sole target of this deterioration, since all components of the articular surface seem to be affected. In recent times, this paradigm shift has led to an ongoing review of therapeutic management schemes for these patients, wherein glucosamine supplements remain cornerstone prescriptions in clinical practice, both by primary attention of physicians and specialists.
Articular cartilage, a fundamental component of the osteoarticular system, is the main degradation target, yet other structures are also affected including subchondral, capsular, synovial, and periarticular soft tissue. Still, the principal disruption occurs within the chondrocyte, with an unbalance between the synthesis and degradation of extracellular matrix, because of an excessive local release of proteolytic enzymes, and a progressive deceleration of cartilage reparation.
In addition, a vast catalogue of bioactive molecules is synthesized at the chondral level, including proinflammatory cytokines IL-1, IL-8, IL-17, IL-18, and TNF-alpha”, as well as free radicals (nitric oxide), growth factors (TGF-Beta), and lipidic mediators (Prostaglandin E 2 , Leukotriene B 4 ) . This inflammatory component develops primarily at the synovial membrane, coexisting with other degenerative mechanisms, and has led research efforts to contemplate therapeutic interventions directed to the stimulation of cartilage synthesis, modulation of inflammation, and regulation of chondrocyte metabolism.
Glucosamine use for attenuating OA symptoms
GluN (2-amino-2-deoxy-D-glucose) is an aminomono-saccharide derived principally from chitin, a compound found in the exoskeleton of certain marine invertebrates. GluN is an essential noncellular component of connective tissue, cartilage, ligaments, and other structures. N-acetylglucosamine can be organically synthesized through the hexosamine pathway, an alternative metabolic route to glycolysis, which is esteemed to consume up to 5% of glucose in adipocyte cultures.
Parallel studies by Reginster et al. and Pavelk´a et al. demonstrated the disease-modifying ability of glucosamine sulfate supplements, by ascertaining improvement of symptomatology and prevention of articular space loss in knee OA patients at a 3-year follow-up. Furthermore, results from a subsequent follow-up on these patients at an average of 5 years suggested that treatment with glucosamine sulfate for at least 12 months may prevent the need for knee arthroplasty, revealing the profound extent of the disease-modifying power of this compound.
The effects in the short-medium term have been evaluated by studies such as the GUIDE Trial , which confirms previous reports regarding the significant improvement glucosamine sulfate yields on symptoms of knee OA, in the range or even superior to what exerted by a first line NSAID or acetaminophen.
Nevertheless, it must be noted that in other reports, benefits do not seem to be present in all analyzed subjects, but only in specific subgroups with distinctive clinical features. This has been exemplified by Clegg et al., who after utilizing glucosamine hydrochloride in their study—a valuable methodological aspect for the comparison of results—could not prove this version of the supplement to reduce pain after 24 weeks in knee OA patients with mild articular pain. These variations in the utilized supplements are indeed very influential. Great-scale research has shown that the use of different commercial brands could factor into results, as suggested by Towheed et al., in their meta-analysis of over 20 randomized controlled trials; only formulations of glucosamine sulfate manufactured by Rotta Laboratories displayed effectiveness in the symptomatic management of patients with OA of the knee, while with other presentations, no statistically significant results were obtained.
Although most studies tend to favor the effectiveness of these compounds in subjects with OA at least through minimal or indirect evidence, especially as disease-progression modulators, no evidence exists of chondroprotective effects of glucosamine in a preventive context This fits with the main findings of in vitro studies, which suggest a predominantly anticatabolic effect in cell cultures. Several molecular mechanisms are implied, including the inhibition of catabolic enzymes, such as metalloproteases, phospholipase A 2 and aggrecanase-2 as well as the reversal of the effects of IL-1# and cyclooxigenase-2, and inhibition of NF-KB signaling. This impact in energetic metabolism and oxidative stress appears to be triggered not only with the consumption of glucosamine alone, but also when accompanied with chondroitin sulfate. These effects have been observed to be more consistent with glucosamine sulfate rather than hydrochloride.
Nevertheless, a great proportion of these experimental reports employ glucosamine concentrations much higher than those obtained through the oral ingestion of supplements, hindering the extrapolation of these findings to in vivo studies. Regarding studies in animal models, findings are similar to in vitro results, with modifications predominantly in synovial inflammation, cartilage degradation, and bone resorption, primarily through the repression of proinflam-matory cytokine genes. Ultimately, the heterogeneity in experimental reports resembles its clinical counterpart, with important differences in the types of supplements used, as well as doses and other characteristics which should be unified in future studies. Harmonizing these criteria is a priority in order to accurately and successfully extrapolate molecular mechanisms to human subjects in the clinical scenario.
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