New concepts in the pathophysiology and treatment of osteoarthritis

Osteoartritis je kronična bolest obilježena degeneracijom zglobne hrskavice i okolne kosti, što može uzrokovati bol i gubitak funkcije zgloba. Prvenstveno 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 vremena smatrao degenerativnom bolešću zglobova koja progredira starenjem, no otkriveni su patofiziološki mehanizmi koji nemaju veze sa starenjem. Dolazi do neravnoteže između proupalnih i protuupalnih citokina te upale sinovijalne ovojnice. Aktiviraju se različite proteaze, kao što su matriks metaloproteinaze i agrekanaze. Potiče se stvaranje dušikova monoksida koji inhibira sintezu izvanstaničnog matriksa i stimulira apoptozu hondrocita. U krvi se mogu naći biomarkeri koji ukazuju na promjene u metabolizmu hrskavice i kosti te na prisutnost upale: BSP, COMP i CRP. Odumrli hondrociti mogu na sebe vezati kalcij pa dolazi do odlaganja BCP i CPPD kristala. Oni stimuliraju daljnje izlučivanje upalnih medijatora te nekoliko matriks metaloproteinaza. Važnu ulogu imaju adiponektin i leptin koji potiču proizvodnju proupalnih citokina i NO te izlučivanje agrekanaza. Dijagnoza osteoartritisa postavlja se na temelju subjektivnih tegoba bolesnika i objektivnog kliničkog nalaza, a potvrđuje radiološkom pretragom. Liječenje osteoartritisa može biti farmakološko, nefarmakološko i kirurško. Farmakološka terapija je simptomatska i uključuje primjenu paracetamola, NSAR, opioidnih analgetika i intraartikularnih injekcija kortikosteroida. Neki od novih koncepata u liječenju bolesti su monoklonalna protutijela koja inhibiraju VEGF, NGF i učinak proupalnih citokina. Istražuju se i učinci blokatora iNOS te intraartikularna primjena mezenhimalnih matičnih stanica. Sve navedene terapijske modalitete potrebno je podrobnije istražiti.Osteoarthritis is a chronic disease characterised by degeneration of joint cartilage and surrounding bone tissue, which can cause pain and loss of joint function. It primarily affects joint cartilage, but also all other joint structures involved in joint function. There are numerous risk factors for developing osteoarthritis, with old age, obesity and injury of the joint being the most important. Osteoarthritis was considered age progressive degenerative disease of the joints, but new patophysiological mechanisms were discovered which are not age-related. Those mechanisms lead to an imbalance between pro-inflammatory and anti-inflammatory cytokines and synovial inflammation. Different proteases, such as matrix metalloproteinases and aggrecanases are activated. Production of NO synthesis inhibits the synthesis of extracellular matrix and stimulates chondrocyte apoptosis. Biomarkers which indicate presence of inflammation and changes in cartilage and bone metabolism, can be found in the blood: BSP, COMP and CRP. Apoptotic chondrocytes can bind calcium which leads to BCP and CPPD crystals deposition. The crystals stimulate further inflammatory mediators and matrix metalloproteinases secretion. Adiponectin and leptin play an important role by stimulating production of pro-inflammatory cytokines and NO, and aggrecanase secretion. The diagnosis of OA is made based on subjective complaints of patients and objective clinical findings and confirmed by radiographic examination. The treatment of osteoarthritis can be pharmacological, non-pharmacological and surgical. Pharmacologic therapy is symptomatic and includes using paracetamol, nonsteroidal anti-inflammatory drugs, opioid analgetics and application of intraarticular corticosteroid injections. Some of new concepts in treatment are monoclonal antibodies which inhibit VEGF, NGF and inflammatory cytokines effects. The effects of iNOS inhibitors and intraarticular application of mesenchimal stem cells are being investigated. All of these therapeutic modalities require further research