Reumatizam, Vol. 64 No. 1, 2017.
Review article
NEW CONCEPTS IN THE PATHOPHYSIOLOGY AND TREATMENT OF OSTEOARTHRITIS
Nikola Ljuban1
Porin Perić
Abstract
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 aff ects 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. Th ose mechanisms lead to an imbalance between proinfl
ammatory and anti-infl ammatory cytokines and synovial infl ammation. Diff erent 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 infl ammation 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 infl ammatory
mediators and matrix metalloproteinase secretion. Adiponectin and leptin play an important role by stimulating
the production of pro-infl ammatory cytokines and nitric oxide (NO), as well as aggrecanase secretion. Pharmacological
therapy of osteoarthritis is symptomatic and includes the use of paracetamol, nonsteroidal anti-infl ammatory
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 infl ammatory cytokine eff ects. Th e eff ects 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.
Keywords
Osteoarthritis – drug therapy, metabolism, physiopathology; Cartilage, articular – metabolism, pathology; Synovitis – physiopathology; Synovial fl uid – cytology, metabolism; Chondrocytes – metabolism, pathology; Apoptosis; Cytokines – biosinteza, metabolism; Endopeptidases – metabolism; Infl ammation mediators – metabolism; Matrix metalloproteinases – metabolism; Adiponectin – metabolizam; Vascular endothelial growth factor a – metabolism; Analgesics, non-narcotic – therapeutic use; Nitric oxide – biosynthesis; Anti-infl ammatory agents, non-steroidal – therapeutic use; Glucocorticoids – therapeutic use
Hrčak ID:
188322
URI
Publication date:
17.10.2017.
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