NOVI KONCEPTI U PATOFIZIOLOGIJI I LIJEČENJU OSTEOARTRITISA

Nikola Ljuban, Porin Perić

Osteoarthritis is a chronic disease characterized by the degeneration of joint cartilage and surrounding bone tissue, which can cause pain and loss of joint function. It primarily affects the joint cartilage, but also all other joint structures involved in joint function. Th ere are numerous risk factors for developing osteoarthritis, foremost among them old age, obesity, and injury of the joint. Osteoarthritis was considered an age-progressive degenerative disease of the joints, but new pathophysiological mechanisms have been discovered which are not age-related. Those mechanisms lead to an imbalance between proinflammatory and anti-inflammatory cytokines and synovial inflammation. Different proteases, such as matrix metalloproteinases and aggrecanases, are activated. Production of nitric oxide inhibits the synthesis of extracellular matrix and stimulates chondrocyte apoptosis. Biomarkers which indicate the presence of inflammation and changes in the cartilage and bone metabolism can be found in the blood: bone sialoprotein (BSP), cartilage oligomeric matrix protein (COMP), and C-reactive protein (CRP). Apoptotic chondrocytes can bind calcium, which leads to basic calcium phosphate (BCP) and calcium pyrophosphate dehydrate (CPPD) crystal deposition. Th e crystals stimulate further inflammatory mediators and matrix metalloproteinase secretion. Adiponectin and leptin play an  important role by stimulating the production of pro-inflammatory cytokines and nitric oxide (NO), as well as aggrecanase secretion. Pharmacological therapy of osteoarthritis is symptomatic and includes the use of paracetamol, nonsteroidal anti-inflammatory drugs, and opioid analgetics, as wella as application of intraarticular corticosteroid injections. Some of the new treatment concepts are monoclonal antibodies which inhibit vascular endothelial growth factor (VEGF), nerve growth factor (NGF), and inflammatory cytokine effects. The effects of inducible nitric oxide synthase (iNOS) inhibitors and intraarticular application of mesenchimal stem cells are being investigated. All of these therapeutic modalities require further research.

Osteoartritis je kronična bolest obilježena degeneracijom zglobne hrskavice i okolne kosti, što može uzrokovati bol i gubitak funkcije zgloba. Ponajprije zahvaća zglobnu hrskavicu, ali i sve druge zglobne strukture odgovorne za funkciju zgloba. Brojni su rizični čimbenici za razvoj osteoartritisa, a najvažniji su starija životna dob, pretilost i ozljede. Osteoartritis se dugo smatrao degenerativnom bolešću zglobova koja progredira sa starenjem, no otkriveni su patofi ziološki mehanizmi koji nemaju veze sa starenjem. Dolazi do neravnoteže između proupalnih i protuupalnih citokina te upale sinovijske ovojnice. Aktiviraju se različite proteaze kao što su matriksne metaloproteinaze i agrekanaze. Potiče se stvaranje dušikova oksida koji inhibira sintezu izvanstaničnog matriksa i stimulira apoptozu hondrocita. U krvi se mogu naći biomarkeri koji upućuju na promjene u metabolizmu hrskavice i kosti te na prisutnost upale: koštani sijaloprotein (engl. bone sialoprotein – BSP), hrskavični oligomerni matriksni protein (engl. cartilage oligomeric matrix protein – COMP) i C-reaktivni protein (engl. C-reactive protein – CRP). Odumrli hondrociti mogu na sebe vezati kalcij pa dolazi do taloženja kristala bazičnog kalcijeva fosfata (engl. basic calcium phosphate – BCP) i kristala kalcijeva pirofosfat dihidrata (engl. calcium pyrophosphate dihydrate – CPPD). Oni stimuliraju daljnje izlučivanje upalnih medijatora te nekoliko matriksnih metaloproteinaza. Važnu ulogu imaju adiponektin i leptin koji potiču proizvodnju proupalnih citokina i dušikova oksida (engl. nitric oxide – NO) te izlučivanje agrekanaza. Farmakološka terapija osteoartritisa jest simptomatska i uključuje primjenu paracetamola, nesteroidnih antireumatika (NSAR), opioidnih analgetika i intraartikularnih injekcija glukokortikoida. Neki od novih koncepata u liječenju bolesti jesu monoklonska protutijela koja inhibiraju vaskularni endotelni čimbenik rasta (engl. vascular endothelial growth factor – VEGF), živčani čimbenik rasta (engl. nerve growth factor – NGF) i učinak proupalnih citokina. Istražuju se i učinci blokatora inducibilne sintaze dušikova oksida (engl. inducible nitric oxide synthase – iNOS) te intraartikularna primjena mezenhimnih matičnih stanica. Sve navedene terapijske modalitete potrebno je potanje istražiti.