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  • 1. 634 www.japi.org © JAPI • VOL. 53 • JULY 2005Update ArticleOsteoarthritisA Mahajan+, S Verma+, V Tandon*AbstractOsteoarthritis (OA) is a chronic degenerative disorder of multifactorial etiology characterized by loss ofarticular cartilage and periarticular bone remodelling. OA causes joint pain, typically worse with weight-bearing and activity as well as can manifest with stiffness after inactivity. It can present as localized, generalizedor as erosive osteoarthritis. Primary osteoarthritis is mostly related to aging, whereas, secondary osteoarthritisis caused by another disease or condition. X-rays, arthrocentesis and arthroscopy remain the main diagnostictools. Blood tests are performed to exclude diseases that can cause secondary osteoarthritis. The treatment ofosteoarthritis includes non-pharmacological management, pharmacological treatment in the form of drugswhich can modify symptoms, symptomatic slow acting drugs for OA or structure modifying OA drugsdepending upon the clinical requirement of the patient. Patients with persistent pain and progressive limitationof daily activities despite medical management may be the candidates for surgery. ©hospitalisation due to its frequent use. There use mayhave a significant impact on overall cost of therapy inpatients of OA in spite the fact that NSAIDs are not verycostly.6,7Hence,OArepresentsamajorcauseofmorbidityand disability, as well as a significant economic burdenon patients and health care resources.8The article reviewsdifferent aspects of OA with an emphasis on earlytreatmentwithdifferentmodalitiestominimizethemajorphysical, mental, social and economic trauma.CLASSIFICATION91) Primary osteoarthritis (idiopathic)A. Localised– Hands – nodal osteoarthritis more than three jointsinvolved– Hip – eccentric, concentric, diffuse– Knee – medial tibiofemoral, lateral tibiofemoral,pattelofemoral– Spine – apophyseal, intervertebral, spondylosisB. Generalised1. Small (peripheral) joints2. Large (central) joints3. Mixed and spineC. Erosive osteoarthritis2) Secondaryi) Congenital and developmental disorders, bonedysplasias.ii) Post-surgery / injury – meniscectomy.iii) Endocrine – diabetes mellitus, acromegaly,hypothyroidism, hyperthyroidism,hyperparathyroidism, Cushing syndrome.iv) Metabolic – hemachromatosis, ochronosis, Marfansyndrome, Ehler-Danlos syndrome, Paget disease,gout, pseudogout, Wilson’s disease, Hurler disease,Gaucher disease.v) Rheumatologic– rheumatoid arthritis.vi) Neurological– Charcot joints.+Post Graduate Department of Medicine; *Post GraduateDepartment of Pharmacology and Therapeutics; GovernmentMedical College, Jammu (J and K) India - 180 001.Received : 6.2.2005; Revised : 4.3.2005;Re-revised : 1.6.2005; Accepted : 3.6.2005INTRODUCTIONOsteoarthritis (OA) is a chronic degenerative disorderof multifactorial etiology characterized by loss ofarticular cartilage, hypertrophy of bone at the margins,subchondral sclerosis and range of biochemical andmorphological alterations of the synovial membrane andjoint capsule. Pathological changes in the late stage ofOA include softening, ulceration and focal disintegrationof the articular cartilage; synovial inflammation alsomay occur. Typical clinical symptoms are pain,particularly after prolonged activity and weight bearing;whereas stiffness is experienced after inactivity.1It isprobably not a single disease but represents the finalend result of various disorders as joint failure. It is alsoknown as degenerative arthritis, which commonlyaffects the hands, feet, spine, and large weight-bearingjoints, such as the hips and knees. Most cases ofosteoarthritis have no known cause and are referred toas primary osteoarthritis. Primary osteoarthritis is mostlyrelated to aging. It can present as localized, generalizedor as erosive osteoarthritis. Secondary osteoarthritis iscaused by another disease or condition.1Osteoarthritis(OA) is the second most common rheumatologicalproblem and is most frequent joint disease withprevalence of 22% to 39% in India.2-4This is the mostcommon cause of locomotor disability in the elderly.5Gastrointestinal toxicity is present in 50% of NSAIDsusers and 5.4% develop a more serious event requiring
  • 2. © JAPI • VOL. 53 • JULY 2005 www.japi.org 635vii) Hematological – hemoglobinopathies.viii) Iatrogenic – intra-articular steroids.ETIOLOGYExact etiology is unknown and multiple factorsinteract to cause this disorder.Age : Although advance osteoarthritis may occur inmany young people in early 20’s, the frequency ofcondition escalates markedly in advancing years.Furthermore, older people are found to have rapidradiological progression of osteoarthritis.5,10Sex : The Framingham Knee Osteoarthritis studysuggests that knee osteoarthritis increases in prevalencethroughout the elderly years, more so in women than inmen.11Females are found to have more severe OA, morenumber of joints are involved, and have more symptomsand increased hand and knee OA.12These observationsand others reporting a painful form of hand osteoarthritisafter the menopause suggest that loss of estrogen at thetime of menopause increases a woman’s risk of gettingosteoarthritis,13however few contrary reports arepouring in.14Obesity : Obesity preceeds rather than follow kneeosteoarthritis and indeed weight loss preventsdevelopment of knee osteoarthritis.15Genetic : Hip osteoarthritis has a significant geneticcomponent.16Nodal generalised osteoarthritis is apolyarticular form of osteoarthritis characterized byHeberden’s nodes occurring mainly in women ofperimenopausal age. Heberden’s nodes appear to beinherited independently as an autosomal dominant traitwith greater penetrance in women.17In 1990, Knowltonet al18reported a non-glycine, second position, autosomaldominant Arg-Cys mutation of COL2A1 in an Americanfamily with inherited generalized OA and minorchondrodysplasia. COL2A1 and vitamin D receptor genepolymorphism may also be included within genetic riskprofile.19Bone density : Negative association has been reportedbetween osteoporosis and osteoarthritis at certain sitesparticularly the hip.20Cigarette smoking : Protective influence of smokingon knee osteoarthritis has been reported from variousstudies including Framingham study.21Local factors : Major direct injury particularly ifresulting in a fracture of articular surface is considereda cause of osteoarthritis.22Trauma in college years (meanage 22) increases subsequent prevalence of osteoarthritisin subjects in their 60’s.23Joint location : OA is more common in hip and kneejoint but occur rarely in ankle. Alteration in chondrocyteresponsiveness to different cytokines may be the reasoneg. knee chondrocytes exhibit more IL-1 receptors thanankle chondrocytes and knee chondrocytes expressmRNA for matrix MMP-8.1Other : Chondrocalcinosis,10crystals in joint fluid /cartilage, prolonged immobilization, joint hypermobilityor instability, peripheral neuropathy, prolongedoccupational or sports stress are the important riskfactors for the causation of OA.24PATHOGENESIS1,17Although the etiology of OA is incompletelyunderstood, the accompanying biochemical, structuraland metabolic changes in the joint cartilage has beenwell documented. It is now known that cytokines,mechanical trauma and altered genetics are involved inpathogenesis and that these factors can initiate adegenerative cascade that results in many characteristicalterations in the articular cartilage in OA. Normalhyaline cartilage is composed of chondrocytes embeddedin extracellular matrix which in turn is constituted bywater, type II collagen and proteoglycan. The cartilageremains stable with active degeneration andregeneration occurring in equilibrium. Whatever is thetriggering event, it leads to matrix and cartilagedegeneration on one hand and active chondrocytereplication with enhanced biosynthesis on the otherhand. This leads to a state of homeostasis, known ascompensated OA, in which both repair and degenerationare balanced. After a few years, the reparative process isexhausted. This leaves cartilage degradation unopposedleading to progressive OA. More recently it has becomeapparent that OA is a disease process that affects theentire joint structure, including cartilage, synovialmembrane, subchondral bone, ligaments andperiarticular muscles. This ultimately results intoinflammation, pain and structural damage leading toloss of function (Fig. 1).The structural changes, metabolic, biochemicalchanges in osteoarthritis cartilage and role of growthfactors and cytokines in the pathogenesis of OA isdepicted below.Structural changes17: Mainly are reductions instainable proteoglycan, fibrillation, collagen crumping,chondrocyte multiplication or migration and loss ofcartilage. Initially, localized areas of softening present apebbled texture at surface followed by disruption alongcollagen fiber planes (tangential flaking, verticalfibrillation). As deep clefts are formed in cartilage, nearbymatrix gets depleted of metachromatic materialindicating loss of proteoglycans. Subsequent focalproliferation of chondrocytes occurs as an attempt atlocal self-repair leading to irregularly shaped hyalineand fibro cartilage. Later new bone formation occurs insubchondral bone and at joint margins (osteophytes).Subarticular cysts predominate wherever overlyingcartilage is thin or absent. Separated fragments ofcartilage and bone may form loose bodies, undergodissolution or become incorporated into synovium andproliferate locally. Synovium becomes thick and
  • 3. 636 www.japi.org © JAPI • VOL. 53 • JULY 2005hypertrophied and capsule contracts with infiltrationof lymphoid follicles, lymphocytes and macrophages.Calcification may occur as calcium crystals deposit incartilage with presumed secondary uptake in synovium.Despite loss of bone and cartilage in some parts of joint,net effect of new cartilage and bone formation is anincrease in joint size and remodelling of shape.Metabolic and biochemical changes in osteoarthritiscartilage1,17• Generalised – Increased hydration and swellingwith loss of tensile strength is noticed in early OA,whereas increase in type I collagen synthesis andprogressive fall occurs in proteoglycanconcentration in later stage of OA.• Specific collagens – Initial swelling of collagenfibrillar network with loss of type II collagen, specificcleavage of collagens and loss of tensile strengthwith increased content of collagen type IV. Type IIIand X collagen are also synthesized.• Proteoglycans – Increased extractability anddecrease in monomer size because of specificcleavages by aggrecanases and metalloproteinases.• Cytokines, proteinases and inhibitors – There isincrease in pro-inflammatory cytokines,aggrecanases, MMPs (matrix metalloproteinase),cathepsins and decrease in overall inhibitors (TIMPetc.).Of the three major MMPs (1, 8, and 13) that degradenative collagen, MMPs -13 is most important, as itpreferentially degrades type II collagen whoseexpression is greatly increased in OA. The aggrecanasesbelong to a family of extracellular proteases known asdisintegrin and metalloproteases with thrombospondinmotifs (ADAMTS). ADAMTS-4 and ADAMTS-5 appearto be major enzymes in cartilage degeneration in arthritis.Where as, IL-1beta synthesized by mononuclear cells(including synovial cells) in inflamed joint is consideredby many investigators as a prime mediator in cartilagematrix degradation and stimulates synthesis andsecretion of many degradative enzymes in cartilageincluding latent collagenase, stronelysin, gelatinase andtissue plasminogen activator.The balance of active and latent enzymes is controlledto some extent by at least two enzyme inhibitors: TIMPand plasminogen activator inhibitor-1(PAT-1).Which inturn are reglated by TGF-beta. However, the imbalancebetween proteoglycan synthesis and degradation isimportant in pathogenesis of cartilage breakdown.Growth Factors and Cytokines1, 17Anabolic— TGF (tissue growth factor beta- 1, 2 & 3) help inchondrocyte proliferation, matrix synthesis,modulate effects of IL-1 and increases proteinaseinhibitors.— Fibroblast and platelet derived growth factors alsohelp in differentiation and proliferation ofchondrocytes and MMP production.— Insulin growth factor-1(IGF-1) increasesglycosaminoglycan (GAG) and collagen synthesis.— Bone morphogenetic proteins increase matrixsynthesis.Catabolic— Interleukin-I (IL-1) and tumor necrosis factor (TNF-a) increase MMPs, inhibit GAG synthesis and canfurther potentiate the degenerative cascade.— Oncostatin-M combines with IL-1 and TNF topromote matrix breakdown.— Others like IL-17 and IL-18 increase expression ofIL-1bð and IL-6 and increase MMP.— NO (nitric oxide) is a major catabolic factor producedby chondrocytes in response to proinflammatorycytokines such as IL-I beta and TNF-alpha. NO caninhibit collagen and proteoglycan synthesis, canactivate MMPs and cause an oxidative injury as wellas produce apoptosis leading to degradation ofarticular cartilage.— Prostaglandins effects on chondrocytes metabolismare complex and include enhanced type II collagensynthesis, activation of MMPs, and promotion ofapoptosis. In cartilage explants, IL-1beta inducesCOX-2 expression and PGE2production coordinatewith proteoglycan degradation. Moreover, COX-2inhibition prevents IL-1beta induced proteoglycandegradation.Fig. 1
  • 4. © JAPI • VOL. 53 • JULY 2005 www.japi.org 637Regulatory— IL-6 increases proteinase inhibitors production andproliferation of chondrocytes while IL-4, IL-13 andinterferon ³ oppose effects of proinflammatorycytokines.— IL-1 receptor antagonist blocks effect of IL-1.CLINICAL FEATURES1,10,17Symptoms : Pain is the chief complaint. This is due tostimulation of capsular pain fibers, mechanoreceptors(increased intra-articular pressure due to synovialhypertrophy), periosteal nerve fibers and by perceptionof subchondral microfractures or painful entheses andbursae. Stiffness is other complaint described as gellingof joint after inactivity with difference in initiatingmovement. Some patients may complain of joint swellingand deformity and coarse crepitus.Signs : Coarse crepitus, due to irregularity of articularsurface, bony enlargement due to remodelling andosteophytes, deformity, instability, restricted ability andstress pain.Nodal generalized osteoarthritis : Present commonlyas polyarticular, finger I-P joint involvement, Heberden(distal I-P joint) and Bouchard (proximal I-P joint) nodes.There is female predominance peaking aroundmenopause and marked familial predisposition.Typically patient is a woman aged 40-60 yearsdeveloping discomfort followed by swelling of singlefinger inter-phalangeal joint, later involving another I-Pjoint within few months and then another producingstuttering onset of polyarthritis of distal and proximal I-P joints.Erosive osteoarthritis : Uncommonvariety,withhandI-P joint involvement, inflammatory signs, erosion insubchondral regions in radiography and tendency forankylosis of I-P joints. Subchondral erosive change maylead to ‘Gull’s wing’ as remodelling occurs.Large joint osteoarthritisKnee : Most commonly affected by osteoarthritis,usually bilateral, often occurs in association with handosteoarthritis especially in women.25,26Invariably focalwith principal sites involved being (i) medialtibiofemoral compartment with severe bone and cartilageattrition at this site resulting in various deformities; (ii)patellofemoral compartment (lateral > medial) becauseof its intimate relationship with the quadricepsmechanism leading to greater functional impairment.27Hip : Superior pole osteoarthritis is commonest withfocal cartilage and loss in superior part of joint.Osteophyte formations are prominent at lateralacetabular and medial femoral margins with thickeningof cortex of medial femoral neck by periostealosteophytes. Central medial osteoarthritis is lesscommon, with more central joint space loss with lessfemoral neck buttressing. More associated with nodalosteoarthritis.Osteoarthritis at other joint sitesOsteoarthritis of spinal apophyseal joints (lowercervical and lower lumbar segments), firstcarpometacarpal and/or first metatarsophalangealjoints is common and may occur as a part of pattern ofgeneralised osteoarthritis or as an isolated feature (Table1).The diagnosis of OA is essentially clinico-radiological.INVESTIGATIONSX-rays are still the main diagnostic tool howeverarthroscopy, ultrasound, MRI, CT scan etc. are usedspecially for experimental studies and not recommendedfor routine clinical use. Plain radiographs can show jointspace narrowing, osteophytes, sclerosis andsubchondral radioluscencies.31,32Other features likeeffusions, loose bodies, joint alignment, subluxation,chondrocalcinosis, collapse due to avascular necrosisare also noticed. Modified radiographic techniques withhigher magnification and resolution may detect earlysubchondral bone abnormalities by stereoscopeTable 1Classification criteria for osteoarthritis of the hipTraditional formatHip pain plus at least two of the followingESR of less than 20 mm per hourFemoral or acetabular osteophytes on radiographsJoint space narrowing on radiographs (superior, axialand or medial)Classification-Tree formatHip pain plus femoral or acetabular osteophytes onradiographs orHip pain plus joint space narrowing on radiographs and anESR of less than 20 mm per hour.28Classification criteria for idiopathic osteoarthritis ofthe kneeTraditional formatKnee pain plus osteophytes on radiographs and at least one ofthe followingAge more than 50 yearsMorning stiffness lasting 30 minutes or lessCrepitus on motionClassification-Tree formatKnee pain and osteophytes on radiographs orKnee pain plus patient age of 40 years or older,Morning stiffness lasting less than 30 minutes and crepitus onmotion.29Classification criteria for osteoarthritis of the handHand pain, aching or stiffness plusHard tissue enlargement of two or more of 10 selected jointsPlusFewer than three swollen metacarpophalangeal joints PlusHard tissue enlargement of two or more distal interphalangealjoints orDeformity of two or more of 10 selected joints.30(10 selective joints are 2ndand 3rdDIP joint, 2ndand 3rdPIP jointand 1stcarpo-metacarpal joint of both hands)
  • 5. 638 www.japi.org © JAPI • VOL. 53 • JULY 2005reconstruction.33Radionucleide studies may detectabnormalities before radiographic signs are identified.Arthrocentesis and laboratory testing may help identifyan underlying cause of secondary OA.Radiological findings of specific joints10Hand : Single postero-anterior view is satisfactory.Bone sclerosis, focal narrowing and lateral subluxationaccompanied by erosions and in case of erosiveosteoarthritis, all changes of osteoarthritis plussubchondral bone erosion-gullwing appearance may benoticed.Knee :Views –A. Standing anteroposterior (weight-bearing).B. Lateral.C. Notch patellar views (sunrise view)1. Posteroanterior intracondylar (PAIC)2. Tangential patellarFindings –A. Joint space narrowing1. Medial tibiofemoral joint space narrowing2. Patellofemoral joint space narrowing3. Lateral joint space narrowing to lesser extentB. New subchondral bone formationC. Tibia lateral subluxationD. Medial osteophytes formation is most prominentinitiallyHip : Single non-weight bearing A-P view of pelvis isusually satisfactory and has advantages of incorporatingboth hips on same radiograph.Sacroiliac jointOsteophyte and joint space loss may need to bedistinguished from inflammatory sacroiliitis.Osteoarthritis causes more focal space narrowing andsclerosis with overlying osteophytes, usuallyanterosuperior/inferior and is identified bydiscontinuity of trabecular lines across joint.Foot : Posteroanterior radiograph of foot.Spine : More in lower cervical and lumbar spine andmay also in facet joints (cervical region). Lateral, A-Plumbosacral and cervical views are appropriate.MANAGEMENT OF OSTEOARTHRITISGoals of managing osteoarthritis include controllingpain, maintaining and improving range of movementand stability of affected joints and limiting functionalimpairment .34NON-PHARMACOLOGICAL MANAGEMENTEducation, behavioral intervention, weight loss, lowerextremity strengthening exercise for 20-30 minutes perday, quadriceps strengthening, gait training, active rangeof motion of hip, knee and ankle, instructions in use ofcane, graded elastic band use and pool therapy aremodestly effective in reducing pain and disability.35Mechanical aids in the form of shock-absorbing footwearwith good mediolateral support, adequate arch supportand calcaneal cushion are also helpful. Lateral heelwedges may reduce pain related to osteoarthritis ofmedial tibiofemoral compartment36and applyingadhesive tapes to patella can provide relief inpatellofemoral osteoarthritis.37PHARMACOLOGICAL MANAGEMENTI. Symptom modifying drugsAcetaminophen is often effective in osteoarthritis,associated with fewer adverse reactions than NSAIDsand is recommended as initial therapy for osteoarthritisin addition to non-pharmacological interventions.38Salicylates and traditional NSAIDs are considered onlyfor patients who do not obtain adequate pain relief withparacetamol.39COX-2 inhibitors can be considered foruse because of better gastrointestinal tolerability.Celecoxib, etoricoxib in the dose of 60 mg/day andvaldecoxib 10mg/day are as efficacious as non-selectiveNSAIDs in pain relief.40,41However recent studies arechallenging the cardiovascular safety of COX-2inhibitors.42Misoprostol as co- therapy in selectivepatients requiring chronic NSAIDs treatment may helpto prevent gastric ulcers.43Opioids (codeine) and paracetamol in combinationprovide better analgesia than paracetamol alone.44Treatment with tramadol results in statisticallysignificant and clinically important and sustainedimprovement in pain, stiffness, physical function, globalstatus and sleep in patients with chronic pain.45Tramadol 37.5 mg / Acetaminophen 325 mgcombination is also effective and safe for treatment ofosteoarthritis pain.46Topical analgesics (0.025%capsaicin cream 47and other local NSAIDs1) have beenconsidered appropriate as an adjunct to simpleanalgesia, monotherapy for a single symptomatic jointor for patients who cannot tolerate systemic therapy. Themechanism of action of capsaicin is thought to bethrough selective stimulation of unmyelinated type Cafferent neurons, causing the release of substance P. Sucha release reversibly depletes the store of substance P, aneurotransmitter of peripheral pain sensation.1In general, intra-articular corticosteroid injections arebelieved to be most effective in patients with evidence ofinflammation, effusion, or both. Because of concerns overpossible deleterious effects, usually no more than fourcorticosteroid injections per year are given in a particularjoint.1Intra-articular glucocorticoid injection, affordmoderate and short-lived reduction in pain.48Triamcolone hexacetonide (TH) suspension is arelatively long acting corticosteroid commonly used for
  • 6. © JAPI • VOL. 53 • JULY 2005 www.japi.org 639IA injection.49Patients presenting with significantinflammation with demonstrable CPPD crystals in jointhave better symptomatic relief with colchicine.50II. Symptomatic slow acting drugs for OA(SYSADOA)Hyaluronic acid (HA) is a linear polysaccharidecomposed of repeating disaccharide units of N-acetylglucosamine and D-glucoronic acid. Two of these agents-hyalgan and synvis- are approved forviscosupplementation in the United States for use in OAof the knee. Multiple injections spaced 1 week apartprovide reduction in pain and beneficial effect lasts forupto 6 months, much longer than as compared tointraarticular steroids. Synvisc requires three injectionsper course of treatment, whereas hyalgan requires five.They are often mentioned as potential structuremodifying agents but are presently considered assymptom-modifying drugs only. There is an evidencefor an anti-inflammatory effect, a short-term lubricanteffect, an analgesic effect by directly buffering of synovialnerve endings and a stimulating effect on synovial liningcells leading to production of normal hyaluronic acid.1The therapeutic benefit of its multiple intraarticularinjections may be comparable to that of NSAIDs.51HylanGF-20 (synvisc) is a high molecular weight cross-linkedderivative of hyaluronan that has elastoviscousproperties similar to healthy synovial fluid. Its efficacyfor treatment of osteoarthritis knee pain, with lowincidence of local adverse effects, has been demonstratedin different clinical trials.52Hyaluronic acid productsare also being actively investigated in shoulder joint OA,periarthritis and adhesive capsulitis.1Nutraceuticals: Pair of nutritional supplements,namely glucosamine sulphate and chondroitin sulphatehas received significant attention. Glucosamine sulphateis a derivative of the naturally occurring aminomonosaccharide glucosamine, a constituent ofglycosaminoglycan chain in aggrecans and otherproteoglycans found in synovial fluid and cartilage ofjoints. It is a substrate for synthesis ofmucopolysaccharides and there is latency of 4-8 weeksbefore therapeutic effect emerges.53Two randomized,controlled, double blind trials in Belgium54and CzechRepublic55suggested that this drug (1.5 g daily) has asubstantial symptom and structure modifying effect inpatients with mild to moderate osteoarthritis of knee.Chondroitin sulphate similarly provides additionalsubstrates for formation of healthy joint matrix. Evidencealso supports oral administration of chondroitinsulphate to slowly reduce symptoms and to reduce needfor NSAIDs.56It ameliorates the symptoms ofosteoarthritis, though this effect only occurs after longerperiod of time.57Chondroitin has been found to beeffective on Lequesne index,and visual analog scale.Mobility and responding status is also excellent (800mg/day).58Combined use of glucosamine sulphate andchondroitin sulphate in treatment of degenerative jointdisease has become an extremely popularsupplementation protocol in OA.59Other drugs1in this category are ginger extract, whichactually contain salicylate and has inhibitory effect onCOX and lipooxygenase. Similarly oral preparations ofavocado and soy unsaponifiables (ASU) have beenshown in vitro to inhibit IL-6, IL-8, MMPs and stimulatecollagen synthesis. Cat’s claw and shark cartilagetreatment leads to an improvement in symptoms of OA,as they also contain chondroitin sulphate. Most recentlyanother compound (S- Adenosyl methionine), an oxygenradical scavenger has been shown to reduce pain in OAbut still larger trials are awaited.III. Structure modifying OA drugs (SMOADS) /chondroprotective1,10Tetracyclines are inhibitors of tissuemetalloproteinases. This could be due to their ability tochelate calcium and zinc ions. Minocycline anddoxycycline have been shown to inhibit articularcartilage collagenase activity, prevent proteoglycan cellloss, cell death and deposition of type X-collagen matrix.Glycosaminoglycan polysulfuric acid (GAGPS), knownas arteparon, work through reducing the collagenaseactivity and has shown promising results. Similarlyother agents like glycosaminoglycan peptide complex(GC-P) known as rumalon has shown to increase thelevels of tissue inhibitors of metalloproteinase, whilepentosan polysulfate (cartrofen) inhibits granulocyteelastase. However, larger clinical trials have yet to provetheir structure modifying activity. Diancerin and itsactive metabolite rhein has the capability to inhibit IL-Ibeta in human synovium. It has improved pain score inpatientsofOAaswellasithasbeenproposedasstructuremodifying drug for OA. Moreover disease modificationpotential of agents like glucosamine, hyaluronan,growth factors and cytokine manipulation, gene therapyas well as chondrocyte and stem cell transplant needsfurther evaluation.Other : Various other therapies includetranscutaneous nerve stimulation, local massage,thermal modalities, acupuncture, amitriptyline, painmanagement counseling and support groups. Assistivedevices in knee osteoarthritis, physical therapy in formof knee sleeves, cane or walker and occupational therapyare modalities, which can be very useful.1,10Surgery : Patients with persistent pain andprogressive limitation of daily activities despite medicalmanagement may be referred for surgical interventionto an orthopedic surgeon.60In conclusion, the treatment of OA includes a varietyof possible non-pharmacological, pharmacological andsurgical interventions. Treatment should be tailored toindividual and will consist of a combination of availablemodalities.
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AustPresc 2004;27:61-3.54. Reginster JY, Deroisy R, Rovati LC, et al. Long-term effects ofglucosamine sulphate on osteoarthritis progression: arandomised, placebo-controlled clinical trial. Lancet2001;357:251-6.55. Pavelka K, Gatterova J, Olejarova M, et al. Glucosaminesulfate use and delay of progression of knee osteoarthritis: a3-year, randomized, placebo-controlled, double-blind study.Arch Intern Med 2002;162:2113-23.56. Kelly GS. Role of glucosamine: sulfate and chondroitinsulfates in treatment of degenerative joint disease. AlternMed Rev 1998;3:227-39.57. Bijisma JW. Glucosamine and chondroitin sulphate as apossible treatment for osteoarthritis. Ned Tijdschr Geneeskd2002;146:1819-23.58. Ricky F, Bruyere O, Ethgen O, et al. Structural andsymptomatic efficacy of glucosamine and chondroitinsulphate in knee osteoarthritis: a comprehensive meta-analysis. Arch Intern Med 2003;163:1514-22.59. Bruyere O, Pavelka K, Rovati LC, et al. Glucosamine sulfatereduces osteoarthritis progression in postmenopausal womenwith knee osteoarthritis: evidence from two 3 year studies.Menopause 2004;11:134-5.60. Chapman AB, Feller JA. Therapeutic arthroscopy for kneeosteoarthritis: time to reconsider? Med J Aust2003;179:179-80.DOCTOR 2004 SoftwareA highly advanced, easy to use, economical and revised medical software package made just for you.CLINICAL : Case sheets and speciality sheets; prescription autodose, autoallergy, contraindication,interaction alert, fonts option (Hindi/Tamil etc.). Allows auto-filling with very little typing needed. Detailedlab, PDR, auto-case summary, certificates, letters; detailed diet adviser.ADMINISTRATIVE : Appointment scheduler; finance billing; salary, room, manpower management;drug store, detailed patient statistics and inventory. 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