Osteoarthritis
John F. Beary III
Michael E. Luggen
KEY POINTS
Osteoarthritis (OA) is the most common musculoskeletal problem in patients older than 50 years, and affects 21 million Americans.
OA is a disease that involves all tissues of the joint organ, and is characterized by focal degeneration of joint cartilage and by new bone formation/osteophytes.
Risk factors for OA include aging, increased joint loading from obesity, muscle weakness (e.g., quadriceps weakness in knee OA), and lower limb alignment abnormalities (e.g., varus/valgus deformities).
Most subjects older than 55 years will have radiographic signs of OA at some locations in their skeletal system. However, many of these radiographic OA sites are asymptomatic, and some of them are only intermittently symptomatic.
There are no commonly available clinical laboratory tests useful in the diagnosis or routine management of OA. If an elevated C-reactive protein (CRP), abnormal hematology profile, high titer rheumatoid factor (RF), or abnormal clinical chemistry tests are obtained, consideration should be given to diagnoses other than OA.
Treatment of OA is symptomatic using nonpharmacologic modalities and analgesics/anti-inflammatories. There are currently no structure-modifying OA drugs (SMOADs) approved by the Food and Drug Administration (FDA).
When a knee joint or hip joint fails due to OA disease, total joint prosthetic surgery is very successful when performed by an experienced surgeon who does a high volume of procedures. A prosthetic knee or hip joint can be expected to last 20 years or so as long as the patient uses it sensibly.
Osteoarthritis (OA) is the most common musculoskeletal problem in individuals older than 50 years. It is characterized by focal degeneration of joint cartilage and formation of new bone in the form of osteophytes at the base of the cartilage lesion in the subchondral bone and at the joint margins. During the past two decades, OA has come to be viewed as a disease involving the entire joint organ (bone, cartilage, and supporting elements) rather than as primarily a problem of the cartilage alone. Although it may be initiated by multiple factors, including genetic, developmental, metabolic, and traumatic causes, OA involves all tissues of the diarthrodial joint.
OA is the result of both mechanical and biologic events that destabilize the normal coupling of degradation and synthesis of articular cartilage and subchondral bone. Ultimately, OA is manifested by morphologic, biochemical, molecular, and biomechanical changes of both cells and matrix.
PREVALENCE
Primary OA is the most common form of arthritis in North America and Western Europe and affects 21 million Americans. The natural history of the disease takes approximately 20 years to be expressed; therefore, most patients are older than 60 years. OA results in 68 million lost workdays/year and 4 million hospitalizations/year. Approximately 100,000 patients in the United States are unable to walk from their bed to the bathroom because of OA. OA of the knee is the second leading cause of disability, following heart disease, in older individuals.
Radiographic surveys reveal that most subjects older than 55 years have radiographically defined disease. It must be emphasized, however, that most radiographically defined OA is not symptomatic.
Women older than 55 years are affected by OA more than are men. From the ages of 40 to 55, there is little difference in the prevalence of OA between men and women. Studies of ethnic groups in the United States reveal that African American women are more likely to get knee OA than are whites.
ETIOPATHOGENESISI. PRIMARY OA
The forces exerted on the normal joint by motion and weight-bearing are dissipated by joint cartilage, subchondral bone, and surrounding structures (joint capsule and muscle). Joint cartilage has unique properties of compressibility and elasticity, attributable to the presence of an intertwined mesh of both collagen and proteoglycan (PG). Cartilage collagen is type II collagen and forms a three-dimensional network of cross-linked fibers that create the structural framework for cartilage. PGs are large molecules that individually consist of a protein core with negatively charged glycosaminoglycan side chains composed of keratan sulfate and chondroitin sulfate.
PGs exist mostly as aggregates and are attached as side chains by a link protein to a core of hyaluronic acid. The PGs bind large amounts of water molecules, which are released when the cartilage is compressed, and recaptured when compression is removed. The primary PG of articular cartilage is termed aggrecan and gives cartilage the ability to undergo reversible deformations.
PGs exist mostly as aggregates and are attached as side chains by a link protein to a core of hyaluronic acid. The PGs bind large amounts of water molecules, which are released when the cartilage is compressed, and recaptured when compression is removed. The primary PG of articular cartilage is termed aggrecan and gives cartilage the ability to undergo reversible deformations.
Primary OA is a multifactorial disease process that involves the joint constituents (chondrocytes, collagen, PGs, subchondral bone, and synovial membrane) in various ways. Although a precise pathogenesis has not been elucidated, the following factors are germane to the development of primary OA:
Aging bone and cartilage. The ability of articular cartilage to withstand fatigue testing diminishes progressively with age. No specific biochemical defect of aging cartilage has yet been identified. However, abnormalities of aging human chondrocytes include decreased cell division and decreased mean telomere length, consistent with chondrocyte senescence.
Mechanical factors (wear and tear)
Accumulated microtrauma causes changes in subchondral bone, which is likely to affect the ability of a joint to absorb the forces associated with constant loading, thereby leading to degeneration of cartilage. This factor may account for occupational OA, such as that seen in the metacarpophalangeal (MCP) and shoulder joints of boxers, elbows of jackhammer operators, knees of basketball players, ankles of ballet dancers, and spines of coal miners.
Lower limb alignment. Varus knee deformities have been shown to be a risk factor for the development of OA in the medial compartment of the knee. Abnormal joint stresses lead to activation of cartilage-damaging enzymes. This has important therapeutic significance, because the re-establishment of joint alignment and mechanics to as near normal as possible, along with decreased trauma to the weight-bearing joints due to decrease in body weight, can have profound positive effects.
Genetic factors. It is known that factors such as the collagen content of cartilage and the ability of chondrocytes to synthesize PGs are genetically determined. Polymorphisms of the type II collagen gene have been identified in several families affected with premature OA. It is likely that changes in the amino acid composition of type II collagen make the collagen less able to handle mechanical stresses, and more susceptible to proteolytic degradation that is set up by abnormal joint stresses.
Biochemical factors. The principal early change in cartilage affected by OA is a decreased content of PGs, with collagen content remaining normal. The loss of PGs causes biomechanical problems, such as a loss of compressive stiffness in the cartilage, decreased elasticity, and an increase in hydraulic permeability. Later, collagen unravels and is lost because of increased enzyme activity in the form of matrix metalloproteinase.
II. SECONDARY OA: PATHOGENESIS
Disorders that damage joint surfaces and cause cartilage changes characteristic of OA include the following:
Mechanical incongruity of the joint
Congenital, genetic, and developmental disorders such as hip dysplasia, slipped femoral capital epiphysis, multiple epiphyseal dysplasia, Marfan’s syndrome, and Ehlers-Danlos syndrome.
Prior joint trauma.
Prior joint surgery, such as meniscectomy.
Prior joint-damaging, inflammatory joint disease such as rheumatoid arthritis (RA) or infectious arthritis.
Prior bone disease, such as Paget’s disease or osteonecrosis.
Bleeding dyscrasias. Hemarthrosis affects 90% of patients with hemophilia, most commonly in the knee, ankle, and elbow. With recurrent hemarthrosis, a proliferative synovitis occurs, which promotes development of secondary OA.
Neuropathic joint disease. Loss of pain or proprioceptive sensation leads to decreased joint protection and subsequent secondary OA. Examples of diseases responsible for the development of neuropathic arthropathy include diabetes, syphilis, pernicious anemia, spinal cord trauma, and peripheral nerve injury. Radiographic findings reveal the most severe and extensive forms of OA changes with loss of
cartilage, exuberant osteophyte formation, bizarre bony overgrowth, fragmentation of subchondral bone with pathologic fractures, and eventual disintegration of the joint structure.
Excessive intra-articular steroid injections. Judicious use of steroid injections is helpful in the management of OA. However, injecting a joint more than four times in 1 year could lead to damage. For example, although intra-articular injection relieves knee pain in football players, it could also mask pain that has a protective function and lead to overuse of an already damaged joint, thereby leading to premature knee OA.
Acromegaly.
Cushing’s disease and long-term corticosteroid therapy through the mechanism of osteonecrosis. Corticosteroids inhibit osteoblast function and may also cause a secondary hyperparathyroidism, which activates osteoclasts and so accelerates subchondral bone damage.
Crystal arthropathies. Calcium pyrophosphate dihydrate deposition (CPPD) disease is strongly associated with OA. Basic calcium phosphate crystals play a key role in the destructive arthropathy of large joints, known as the Milwaukee’s shoulder syndrome.
Gout
Ochronosis. These patients lack homogentisic acid oxidase, which results in increased urinary excretion of homogentisic acid and increased binding of homogentisic acid to connective tissue. The latter presumably is responsible for the secondary OA seen in this disorder. The pigment is deposited in cartilage, skin, and sclera. Degenerative disease of the spine with calcification of the intervertebral discs is characteristic.
Wilson’s disease. Premature OA, pseudogout, and chondromalacia patellae are articular manifestations of this disorder involving copper metabolism.
Hemochromatosis. Hemosiderin granules are deposited in cartilage. CPPD crystals are also associated with this disease. The arthropathy of hemochromatosis characteristically involves the second and third MCP joints.
PATHOLOGY OF OSTEOARTHRITISVarious features are seen in cartilage, bone, and other tissues as the disease progresses and include the following:
I. STRUCTURAL BREAKDOWN OF CARTILAGE
In the order of progression, this process consists of the following: (a) superficial fibrillation and fissuring; (b) focal and diffuse erosions of the cartilage surface; and (c) thinning and complete denudation of cartilage.
II. Changes in subchondral bone
include subchondral bony sclerosis, cyst formation, and bone thickening with eburnation.
III. Reactive proliferation of new bone and cartilage
at the joint periphery produces osteophytes. It has been previously shown that the bony changes of subchondral cortical sclerosis and osteophytosis precede changes in articular cartilage thickness, measured radiographically. In addition, there are local osteoporosislike changes in the cancellous bone of the proximal tibia of patients with OA.
IV. OTHER TISSUE CHANGES
Some mild degree of synovitis can be expected, perhaps as a contributor to joint damage and/or as a consequence of attempts to remove degenerative bone and cartilage debris from the synovial space. Additional pathologic changes in the joint organ include degeneration of menisci and periarticular muscle atrophy.
CLINICAL MANIFESTATIONSI. PRIMARY OA
Localized OA. Heberden’s nodes [bony protuberances arising from distal interphalangeal (DIP) joints] without other joint involvement represent the most common form of primary OA. Family studies reveal that genetic factors are
important in the development of Heberden’s nodes. These nodes are ten times more common in women than in men and tend to be seen in both mothers and their daughters.
Generalized OA is determined by involvement of three or more joints. Joint features of generalized OA include a predilection for postmenopausal women and episodic joint inflammation. A familial pattern, associated with Heberden’s nodes, has been reported in a subset of patients with generalized OA.
Erosive OA, also known as inflammatory OA, may be a distinct disease. However, there is also a possibility that erosive OA merely represents the end of the OA spectrum and is characterized by severe disease. DIP and proximal interphalangeal (PIP) joints of the hands are affected. Joint radiographs reveal both osteophytes and erosions.
II. SECONDARY OA
The preceding text lists causes.
Symptoms
Symptomatic patients are usually older than 40 years.
Patients complain of pain of insidious onset in one or a few joints. The pain is often dull and persistent and is poorly localized.
The pain initially occurs after normal joint use and is relieved by rest. As the disease progresses, pain develops even during periods of rest. Joint stiffness lasts less than half an hour in the morning. Knee OA is commonly associated with a “theater sign” in which prolonged sitting leads to stiffness that lasts for a few paces while walking before normal gait returns.
Degenerative changes in the menisci may cause a feeling of “giving way”, and pieces of osteophytes that get broken off can cause locking of the knee.
Systemic symptoms are absent.
Most common sites of involvement are the DIP, PIP, and first carpometacarpal (CMC) joints of the hand and the first metatarsophalangeal (MTP) joint in the foot. Other common areas include the hips, knees, and the lumbar and cervical spine. OA rarely involves the MCP joints, wrists, elbows, and shoulders or ankles, unless secondary OA is present. In general, correlation between joint symptoms and radiographic changes in early OA is poor. However, as the disease progresses, pain resulting from the pathology in bone, which is richly innervated, is more common. Later-stage disease is characterized by osteophytes and radiographic narrowing of joint space, particularly in large, weight-bearing joints such as the knee and hip.
III. PHYSICAL EXAMINATION
Joints may be tender even in the absence of overt inflammation, which does occur on occasion in patients with OA. Pain may occur with weight-bearing, but may be absent on passive range-of-motion testing. Joint enlargement may result from the presence of effusion, synovial hyperplasia, or osteophytes.
In the later stages of disease, there may be a crackling sound called crepitus on movement of the affected joint, gross deformity and subluxation caused by cartilage loss, collapse of subchondral bone, bone cysts, and gross bony overgrowth. However, crepitus alone can be seen in some forms of early OA such as patellofemoral disease in older individuals.Related posts:
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