Research in the field of osteoarthritis concentrates on hyalinecartilage as an important part of the joint as a functional unit(hyaline cartilage, subchondral bone, synovia, joint capsules, ligamentsand muscles). To withstand biomechanical stress, hyaline cartilagecontains a highly organized network of tissue-specific collagens,which is filled with proteoglycans and several noncollagenous matrixproteins. The various components intensively interact with eachother and with the chondrocytes, the cellular element of the cartilage(1).
One of the most prominent alterations that characterizes osteoarthriticcartilage damage is a reduction of proteoglycan content, reflectingan imbalance between synthesis and release of proteoglycans. Bothsynthesis and release depend on the activity of cartilage cells,chondrocytes, in the upper layer of osteoarthritic human knee cartilagewhich appear to be phenotypically altered, leading to diminishedproteoglycan synthesis (2).

The double biochemical nature of proteoglycans allows them to combinein the same macromolecule both a proteic (the core protein) anda saccharidic (glycosaminoglycan chains). Through this structuraldiversity, proteoglycans are highly interactive macromolecules andthus participate in a broad range of matricial and cellular actions.Changes in the metabolism of proteoglycans affects drastically thecartilage and leads to osteoarthritis(3)
Osteoarthritis consists of the progressive loss of articular cartilagethat begins with fraying or fibrillation of the articular surfaceand progresses to exposure of subchondral bone. Attempted repairof the cartilage, remodeling of subchondral bone, and, formationof osteophytes, accompany the degeneration of the articular cartilage(4,5,6).

Once degeneration of the joint begins, it usually progresses inexorably,causing increasing pain and loss of mobility despite attempted repairof the articular surface. The limited capacity of articular cartilagefor repair or regeneration has led to the widely accepted view thatan osteoarthritic joint cannot be restored to normal structure andfunction (7). Even the most effective current treatments for Osteoarthrosisdo not restore the joint (8,9).

Conventional treatments for Osteoarthritis:

Non-operative treatments, including modifications of lifestyle,exercise programs, steroidal and non-steroidal anti-inflammatorydrugs, and physical therapy, can decrease symptoms and improve mobility,but they do not detectably alter the course of the disease for mostpatients. Arthrodesis of degenerated joints relieves pain but sacrificesmobility. Osteotomies of the hip and knee can decrease pain and,in some patients, can lead to formation of a new articular surfacebut the results vary considerably among patients (10). Resectionof degenerated joints and replacement of these joints with implantsfabricated from polyethylene, metal, or another synthetic materialpredictably relieves pain and improves function. However, theseprocedures have important limitations, especially for young, activepatients, primarily because they do not restore an articular surfacewith the mechanical properties and durability of articular cartilage.Moreover, synthetic materials must be fixed to the bone of the patient.Thus, the wear of the implant surfaces limits the life span of theimplant. Within this life span, the bond between the implant andthe bone may fail.
However, recent reports of methods that promote the formation ofnew articular surfaces in localized cartilage defects have createda great interest among scientists and physicians in the possibilitiesfor restoration of osteoarthritic joints (11). For all of thesereasons, treatments that restore the structure and function of osteoarthroticjoints would be appropriately heralded as breakthroughs and couldbenefit many patients.

Patients who have Osteoarthritis, always, seek treatments thatwould repair or regenerate the articular cartilage rather than replacethe joints. Successful restoration of osteoarthritic joints requiresa detailed analysis of the structural and functional abnormalitiesof the involved joint followed by application of a treatment plan.This plan may include use of medications that help to maintain orrestore articular cartilage.

Glucosamine Gel helps maintain and restore Articular Cartilage

Glucosamine sulfate and Chondroitin sulfate

Chondroprotection is a somewhat new field in the therapy of osteoarthritis,which is designed to improve cartilage repair as well as enhancejoint remodeling. It clearly results from both laboratory modelsas well as from studies on human osteoarthritis, that cartilagecontains biological resources to meet the repair of degenerativeinjuries and inflammation. The Glucosamine sulfate and chondroitinsulfate represent the main biological resources for such repair.Since osteoarthritis results from progressive catabolic loss ofcartilage proteoglycans, owing to an imbalance between synthesisand degradation. Standard drug therapy is only of palliative benefitand may exacerbate loss of cartilage. Glucosamine is an intermediatein proteoglycans synthesis, and its availability in cartilage tissueculture can be rate-limiting for proteoglycan production.
Since 1980 and perhaps before, osteoarthritis-modifying drugs wereclinically tested with two main aims: not only stopping or reducingthe cartilage degenerative process after a long-term treatment,but also controlling the symptoms of the disease within a few daysor weeks, thus avoiding or diminishing the use of symptomatic medications.Due to the difficulties of implementing the first aim, the latteraim was more often investigated.
A number of double-blind studies dating from the early 1980s demonstratethat oral Glucosamine decreases pain and improves mobility in osteoarthritis,without side effects. Nevertheless, medical researchers and physicianshave totally ignored this rational and safe therapeutic strategy.These and other safe nutritional measures supporting proteoglycansynthesis, may offer a practical means of preventing or postponingthe onset of osteoarthritis in older people or athletes (12).

The rapid symptomatic response to high-dose Glucosamine in osteoarthritisis explained by (13,14):

• Glucosamine stimulates synovial production of hyaluronic acid (HA) which is primarily responsible for the lubricating and shock-absorbing properties of synovial fluid.
• Many clinical and veterinary studies have shown that intra-articular injections of high molecular weight HA produce rapid pain relief and improved mobility in osteoarthritis.

The importance of Hyaluronic acid (H.A) is due to:

• HA has an anti-inflammatory and analgesic properties.
• It promotes anabolic behavior in chondrocytes.
• As the concentration and molecular weight of synovial fluid HA are decreased in osteoarthritis, reversing this abnormality though giving high-dose Glucosamine may provide rapid symptomatic benefit, and in the longer term aid the repair of damaged cartilage.
• The visco-elasticity of the synovial fluid is entirely due to its HA content.
• HA forms an integral part of the proteoglycans of articular cartilage.
In 1982 another double-blind trial was carried out in 40 out-patientswith unilateral osteoarthrosis of the knee to compare the efficacyand tolerance of oral treatment with 1.5 g glucosamine sulfate or1.2 g ibuprofen daily over a period of 8 weeks. Pain scores decreasedfaster during the first 2 weeks in the ibuprofen than in the glucosaminetreatment group. Although the rate of decrease was slower, the reductionin pain scores was continued throughout the trial period in patientsan glucosamine and the difference between the two groups turnedsignificantly in favour of glucosamine at Week 8. No significantdifferences were observed in swelling or any of the other parametersmonitored. Tolerance was satisfactory with both treatments, withonly minor complaints being reported by 2 patients on glucosaminecompared with 5 patients on ibuprofen (19).
Also in 1982 an open study was carried out by 252 doctors throughoutPortugal to assess the effectiveness and tolerability of oral glucosaminesulfate in the treatment of arthrosis (Pharmatherapeutica. 3(3):157-68,1982). Patients received 1.5 g daily in 3 divided doses over a meanperiod of 50 +/- 14 days. The results from 1208 patients were analyzedand showed that the symptoms of pain at rest, on standing and onexercise and limited active and passive movements improved steadilythrough the treatment period. The improvement obtained lasted fora period of 6 to 12 weeks after the end of treatment. Objectivetherapeutic efficacy was rated by the doctors as ''good'' in 59% ofpatients, and ''sufficient'' in a further 36%. These results weresignificantly better than those obtained with previous treatments(except for injectable glucosamine) in the same patients. Sex, age,localization of arthrosis, concomitant illnesses or concomitanttreatments did not influence the frequency of responders to treatment.Oral glucosamine was fully tolerated by 86% of patients, a significantlylarger proportion than that reported with other previous treatmentsand approached only by injectable glucosamine. The onset of possibleside-effects was significantly related to pre-existing gastro-intestinaldisorders and related treatments, and to concomitant diuretic treatment.

In 1984 a group of 68 patients with mild or moderate gonarthritiswere treated with intra-articular injections of glucosamine sulfateor glycosaminoglycan polysulfate over a period of six weeks. Thetherapy was successful in two thirds of these patients. "Loading"pain was eliminated or improved in about 80%, and signs of synovitishad improved in about 66%. Gait function and mobility were improved.Glucosamine had a superior effect, in particular in mild arthritis,achieving an improvement of pain in 90%, while glycosaminoglycanpolysulfate (chondroitin sulfate) was successful in advanced cases.The tolerance of the two substances was 94%. The results and theunderlying modes of action of the substances are discussed (20).
In 1992 Three double-blind, controlled, parallel groups, randomized,4-6 week trials of glucosamine sulphate versus placebo or the NSAIDibuprofen on a total of 606 out-patients with gonarthrosis. Movementlimitation and pain were scored, and the efficacy goals were strictlypre-determined. Access to other medications was not allowed. Glucosaminewas significantly more effective than placebo, while no differencewas detected in comparison with the NSAID. On the other hand, glucosaminewas as well tolerated as placebo, while the percentage of patientssuffering adverse drug reactions was higher in the ibuprofen group(21).
Since 1992 more attention have been derived towards glucosaminesulfate for the treatment of osteoarthritis. In 1998 a broad dataanalysis of studies has been done on the usefulness of glucosaminesulfate in the treatment of patients with osteoarthritis (22). Pertinentcitations were identified via a MEDLINE search (January 1975-March1997). It has been concluded that osteoarthritis being the mostcommon form of arthritis represents a major cause of morbidity anddisability in the elderly. The main symptom of osteoarthritis ispain and most of the commonly prescribed medications (e.g. acetaminophen,nonsteroidal anti-inflammatory drugs) have been targeted at relievingthe pain. Some of these medications have serious adverse effectsand do not necessarily change the natural course of the disease.Glucosamine sulfate, a nutritional supplement, has recently emergedas an alternative treatment option for patients with OA. The beneficialeffects of this chondroprotective agent have been reported to reverseor at least stop the progression of the disease without inducingserious adverse effects. Limited data from short-term human trialssuggest that glucosamine sulfate administered orally, intravenously,intramuscularly, and intra-articularly may produce a gradual andprogressive reduction in joint pain and tenderness, as well as improvedrange of motion and walking speed. Results of the trials have alsoshown that glucosamine has produced consistent benefits (>50%overall improvement in symptom scores) in patients with OA and that,in some cases, it may be equal or superior to ibuprofen in controllingsymptoms.
In 1999 another review about glucosamine sulfate studies was published(23)and the authors concluded that Glucosamine sulfate''s role in haltingor reversing joint degeneration appears to be directly due to itsability to act as an essential substrate for, and to stimulate thebiosynthesis of, the glycosaminoglycans and the hyaluronic acidbackbone needed for the formation of the proteoglycans found inthe structural matrix of joints. Successful treatment of osteoarthritismust effectively control pain and should slow down or reverse theprogression of the degeneration. Biochemical and pharmacologicaldata combined with animal and human studies demonstrate that glucosaminesulfate is capable of satisfying both of these criteria.
N2 Scientists designed a product with very high efficacy forthe treatment of osteoarthritis, in the form of gel containing theactive ingredients, glucosamine sulfate and chondroitin sulfate,in high concentration. The emulsifier used in the preparation ofthe gel has been modified to allow the achievement of maximal effectof the active ingredient on dermal application. The new productwill help osteoarthritis sufferers get fast, long-term relief frompain, stiffness, and immobility restoring normal functioning articularcartilage without any negative effects one receives from the commonlyprescribed drug. The active ingredients have the ability to permeatethe skin and the fine capillary wall around the joints to be highlyconcentrated in the synovial fluid to stimulate the chondrocytesto synthesize the proteoglycans which is the main building blockof the articular cartilage. The healthy smooth articular surfacehelps good range of joint mobility and reduce the pain of osteoarthritis.

References

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