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Osteoarthritis (OA) can be defined as the degeneration of the hyaline cartilage covering articular surfaces. Secondary effects of the disease include the inflammation of the synovial membrane and subchondral bone (the bone in contact with the cartilage) and the formation of bony growths around the edges of the joint surface. Osteoarthritis causes pain and functional impairment. It is closely linked to age, mostly affecting people in their 50s and 60s, and has a predisposition for the knee, certain joints in the hand (the distal and proximal interphalangeal joints), the hip and the small joints in the spine. However, the disease can occur in any joint and can affect one or more joints (polyarthritis). The etiology of this slow-developing disease is unknown. Sufferers occasionally go through periods of stability that can last years, although in other cases the disease can progress very quickly. Spontaneous improvement is rare. Different developmental stages of osteoarthritis have been identified: I. DESTRUCTION OF THE CARTILAGE: proteolytic damage to the cartilage matrix. II. INFLAMMATION OF THE SYNOVIAL MEMBRANE: fibrillation and erosion of the cartilage surface. Release of degradation products from the synovial fluid. III. REMODELING OF SUBCHONDRAL BONE: the synovial cells consume the degradation products. Production of inflammatory proteases and cytokines.
Fig. 7. Schematic representation of normal cartilage (a) and osteoarthritic cartilage (b). The blue balls denote monomers that bind with hyaluronate (HA) (green). The swelling pressure generated by these molecules is counterbalanced by the tight collagen network (orange-brown), which is strengthened by the intercollagen cross-links (red). In osteoarthritis, the loss of aggrecan molecules allows the remaining proteoglycan molecules to swell and become “decompressed”. The cartilage becomes softer and the pressure as well as shear resistance is reduced.
When this process is altered. Fissuring: Presence of deep cracks in the cartilage. PHYSIOPATHOLOGY OF OSTEOARTHRITIS The physiopathology of OA is not completely understood.The evolution of the disease is clearly shown in the following images: 1 2 3 4 1. but progress is being made. Chondrocytes are the cells responsible for this metabolism. 2. Pro-inflammatory cytokines and proteases participate in the catabolic process. where the final aims are the formation of the extracellular matrix and cell proliferation. Under normal conditions. which results in the destruction of the cartilage matrix and a reduction of cell proliferation. a series of changes occurs in the morphological and biomechanical characteristics of cartilage that make it fail to perform its function. 3. The edema can only be perceived under an electron microscope. in which synthesis (anabolism) and destruction (catabolism) are balanced in a coordinated way. Protease inhibitors and anti-inflammatory cytokines participate in the anabolic process. Fibrillation: Cartilage begins to wear down. Edema of the cartilage: There are no clinical or radiological signs. 2 . the components of the cartilage matrix are gradually replaced. 1. 4. Ulceration-Eburnation: The subchondral bone of the joint surface is exposed.
but its levels are diminished in osteoarthritic cartilage. They are activated by IL-1 (interleukin1). and also inhibits the synthesis of collagen II and proteoglycans. TNF-α has effects similar to those of IL-1. growth factors and nitric oxide The cytokines are soluble proteins secreted by different cells in response to specific signals. They have a short half life and therefore tend to act on cells in the area adjacent to where they are produced. IL-1 (interleukin-1). and triggers apoptosis. which activates collagenase in the presence of stromelysin. It has been observed that osteoarthritic chondrocytes can have twice as many surface receptors of IL-1 than normal chondrocytes. It stimulates metalloproteinase expression. The activity of the metalloproteinases is regulated by the enzymes’ physiological inhibitors and activators. It promotes vasodilatation and permeability in joints by increasing the secretion of TNF-α and IL-β by the leukocytes. Included among the serine proteases is the tissue plasminogen activator (plasmin). The activity of IL-17 is similar to that of IL-1 but to a lesser degree. Cytokines act unlike other enzymes by regulating the activity of other cells. a lysosomal enzyme (intracellular) capable of activating the metalloproteinases.Aggrecanase is a proteolytic enzyme that breaks down the proteoglycans to produce identical fragments found in the synovial fluid. there is a lack of this inhibitor in osteoarthritic cartilage. In normal cartilage the metalloproteinases and their inhibitors are balanced. TGF-β (transforming growth factor beta) and IGF (insulin-like growth factor) participate in their anabolic program. Cytokines. Nitric oxide is a free radical that is synthesized as a result of the oxidation of the amino acid L-arginine through the enzyme nitric oxide synthase (NOS). In fact. Among the thiol proteases. inhibits the proliferation of chondrocytes induced by serum or TGF-β. TNF-α (tumor necrosis factor alpha) and IL-17 (interleukin17) participate in the catabolic program of the chondrocytes. IL-6 and IL-8 (interleukin 6 and 8) are modulators of anabolic and catabolic activity. the most important component is cathepsin B. There is an inhibitor of this activity. IL-1 induces the expression of TNFα receptors in chondrocytes and synoviocytes. As in the other cases. Some of its effects on cartilage are shown in Figure 3: 4 . It also plays a major role in the production of nitric oxide. The inhibitors of the metalloproteinases are the TIMPs (tissue inhibitors of metalloproteinase) and some of them are secreted by the chondrocytes. It also has a physiological inhibitor: the inhibiting protein of the cysteine proteases. IL-1 is the prototype of the molecule that induces a catabolic response.
which can sharply increase the biological effects at different levels. 3) Nitric oxide .1) Factors that trigger osteoarthritis induce the synthesis of nitric oxide by the chondrocytes in articular cartilage. 2) Nitric oxide levels go up in the joint space.
ultimately resulting in the release more inflammatory cytokines and proteases. IGF levels decrease with age and in osteoarthritic processes. Therefore. stromelysin and IL-6 have also been found in synovial tissue. and that loading can modify the composition and function of the metalloproteinase system. In fact. The mechanical loading absorbed and transmitted by this bone appear to be converted into biochemical signals that participate in the anabolic and catabolic programs regulating cartilage homeostasis. there are more trabeculae and less separation between trabeculae. TGF-β and IGF. the bone mineral density of subchondral bone is higher.IL-6 also works in two different ways. intense mechanical loading can affect subchondral bone and contribute to the onset of the pathogenesis of osteoarthritis. It has been shown that collagen integrity varies depending on the loading received. frequent. The formation of the extracellular matrix is primarily stimulated by two growth factors. it performs some anti-inflammatory activity and produces TIMPs. Subchondral bone in osteoarthritis In patients with osteoarthritis. the synovial fluid goes through a major inflammatory process. The action mechanism of IL-6 indicates that it plays an important i1 hTw -2Be in the self-regulation of joint damage and an intermediary -2Be in the nduction of some cell responses to specific i cytokines. given that its participation is necessary so that IL-1 β can inhibit the synthesis of proteoglycans. Secondly. it acts by favoring the osteoarthritic process. However. Collagenase. The effect of TGF-β on the proliferation of chondrocytes is inhibited by IL-1 through a process involving prostaglandin E2 and nitric oxide. IL-8 activates the production of superoxide anions. the matrix will have a different composition depending on the mechanical loading it receives. These mediators are released into the synovial fluid and finally stimulate certain receptors on the surface of the chondrocytes. IL-1 β and TNF-α can induce the production of IL-6. The importance of mechanical loading Mechanical loading of the joint is necessary so that the extracellular matrix maintains its metabolism and composition. Firstly. and also increases the expression of inhibiting factors of metalloproteinases. which are toxic for cells. Large amounts of the pro-inflammatory mediators IL-1 and TNF-α are synthesized. Synovial fluid in osteoarthritis In patients with osteoarthritis. IGF stimulates the proliferation of chondrocytes and favors matrix synthesis. 6 . TGF-β promotes the formation of type-II and type-IX collagen and proteoglycans.
persistent and repetitive use of a joint (especially by top-level athletes) can lead to osteoarthritis in a specific joint. it is not a result of the disease. FACTORS THAT CAN ACCELERATE OSTEOARTHRITIS Age: Osteoarthritis is a disease that appears with age. This is the case of lumbar and knee osteoarthritis among miners. given that such activity increases the risk of early joint degeneration. Obesity: There is a clear relationship between obesity levels and the probability of developing osteoarthritis. among others. and osteoarthritis of the elbow and wrist among pneumatic-drill operators. 2.Both IL-1 β and TNF-α need a mechanism of secondary messengers to perform their functions. they can participate in the anabolic or the catabolic program. Both pathways result in the direct or indirect destruction of the cartilage. Physical Activity: The continuous. There is also a relationship between the level of obesity and the functional severity of the disease. depending on their situation. 7 . Obesity precedes osteoarthritis. IL-1 β stimulates both the nitric-oxide pathway and the cyclooxygenase 2 pathway. together with the fact that the tissue is less able to recover with age. due to wear and tear on the joint produced by use over the years. The table shows the different molecules involved in the anabolic and catabolic process of the chondrocytes: Catabolism Proteolytic Enzymes Collagenases Stromelysin Aggrecanase Anabolism TIMPs Cytokines and growth factors IL-1 TNF-α IL-17 NO Prostaglandin E2 TGF-β IGF Nitric oxide and prostaglandins IL-6 and IL-8 can act as modulators. Work Activity: The development of osteoarthritis has been linked to certain jobs that call for the continuous use of certain anatomical areas over long periods of time. which causes an increase in prostaglandin E2 levels.
Bone Mineral Density: It has been observed that patients with a higher bone mineral density are at greater risk of suffering from osteoarthritis. This may be caused by increased biomechanical stress on the cartilage. which leads to its degradation. especially in the case of cruciate-ligament injuries and meniscal tears. Genetics: Heredity is believed to be a factor in .History of Injury: A major injury is a common cause of knee osteoarthritis. A tear can alter the mechanical function of the joint and make the patient predisposed to osteoarthritis in any other joint.
the pain apphavc19. Symptoms begin gradually and progression is slow.08 6mn8so So o . At first. and disorders in the axes of the lower limbs and the affected areas. but have some characteristics in common.08 -1.1l2 85. The symptoms of osteoarthritis depend on the joints affected. the conditions under which it improves (rest) and worsens (when bearing a load).Osteoarthritis is diagnosed by evaluating symptoms related to the location and characteristics of pain. crepitus.
The most commonly used method at the present time is Huskisson’s Visual Analogue Scale (VAS). No pain (0) (from 0 to 100) Unbearable pain (100) .. in which patients have to rate their level of pain from 1 to 10 or from 0 to 100.
This analysis is particularly useful for ruling out the existence of other inflammatory or microcrystalline processes. Rheumatologists occasionally perform a series of tests to confirm the initial diagnosis and to gain an idea of the severity of the disease and its progression at the structural level. These tests may include: Joint-fluid aspiration: The synovial fluid can be analyzed when viscosity is high and cellularity is low.validated digital image analysis system to observe the progression of: mean thickness. Blood analysis: Blood disorders are not common in osteoarthritic . minimum width of the joint space and surface area.
arthroscopy. CT scan. It was developed by Kellgren and Lawrence and is key in current radiological assessment of osteoarthritis: Grade 0 Clssiifcon a ita Normal Description No characteristic symptoms of osteoarthritis 1 Doubtful Indications of osteophytes Significance doubtful 2 Minimal Definite osteophytes 3 Moderate Moderate narrowing of joint space 4 Severe Joint space very narrow.Other tests include: nuclear magnetic resonance (NMR). A system of radiographic grading of osteoarthritis is also used. ultrasound. bone gammagram. etc. with subchondral-bone sclerosis 12 .
Some of the different kinds of osteoarthritis are described below: Osteoarthritis of the spine In addition to the typical symptoms of the di osteoarthritis HRITIS al eniscusHRITIS surgeryert. CLINICAL SYMPTOMS OF OSTEOARTHRITIS The clinical symptoms of osteoarthritis vary depending on the part of the body affected and certain indications are specific to each joint.5. omo eachc .
flexion is more limited. which become more severe as the disease progresses. Jo . joint swelling appears and is sometimes accompanied by joint effusion and cysts. the symptoms become more evident. pain is felt only when the knee is completely flexed. In initial stages. As the degenerative process advances.The main symptom is mechanical pain with stiffness and functional impairment.
and frequently also with rhizoarthrrally begiredfnted . discomfort disappears or becomes tolerable over time and the joints are only painful when certain movements and exertions are made. reddening. or they may appear suddenly. swelling and functional impairment. as an acute inflammatory reaction with pain.These nodes may begin with just a little or no pain. Osteoarthritis of proximal interphalangeal joints This ailment is generally associated with distal interphalangeal osteoarthritis. Although the deformity remains. Small gelatinous cysts are sometimes observed in the joints.
It is found more frequently in women. with asymptomatic forms and others involving joint effusion accompanied by pain and marked functional impairment.Osteoarthritis of the trapeziometacarpal joints (rhizoarthritis or osteoarthritis of the thumb) Osteoarthritis of the trapeziometacarpal joints is a very frequent form of osteoarthritis of the hand. located in the groin and irradiating to surrounding areas. Osteoarthritis of the hip (coxarthrosis) This is one of the most frequent and incapacitating forms of osteoarthritis. with progressive limping and marked functional limitations. but is usually associated with the presence of Heberden nodes. It sometimes appears by itself. It appears in men and women alike and is frequently the only part of the body suffering from osteoarthritis. 16 . The main symptom is mechanical pain. Stiffness is usually experienced after resting. Clinical manifestations include deformity and local joint pain that varies in intensity. Pain may become intense and cause significant functional impairment. Mobility is reduced. This is the form of osteoarthritis that most restricts the movements of the hand.
. The symptoms are pain and moderate limitation of mobility.Osteoarthritis of the elbow Osteoarthritis of the elbow is not frequent and is usually secondary to trauma or a previous joint disease. when intense. It is usually also associated with trauma or a previous joint disease. Osteoarthritis of the shoulder (omarthritis) Osteoarthritis of the shoulder is not frequent. The symptoms are pain which. but is still the second cause of shoulder pain. is accompanied by stiffness and limited mobility.