51. | Manual of Rheumatology and Outpatient Orthopedic Disorders (LB Spiral Manuals)

Chapter 44 Osteoarthritis

Manual of Rheumatology and Outpatient Orthopedic Disorders

Chapter 44 Osteoarthritis

John F. Beary, III and Michael E. Luggen

Disease classification
Epidemiology
Pathogenesis
Pathology
General clinical presentation
Specific patterns of joint disease
Differential diagnosis
Treatment
Surgical treatment
The prognosis of osteoarthritis

Osteoarthritis (OA) is the most common musculoskeletal problem in people over age 50. It is characterized by focal degeneration of joint cartilage and new bone formation at the base of the cartilage lesion (subchondral bone) and at the joint margins (osteophytes). 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 cartilage problem.

A 1994 National Institutes of Health Conference created the following comprehensive definition: Osteoarthritis is the result of both mechanical and biologic events that destabilize the normal coupling of degradation and synthesis of articular cartilage and subchondral bone. Although it may be initiated by multiple factors, including genetic, developmental, metabolic , and traumatic causes, OA involves all tissues of the diarthrodial joint. Ultimately, OA is manifested by morphologic, biochemical, molecular, and biomechanical changes of both cells and matrix that lead to a softening, fibrillation, ulceration, and loss of articular cartilage; sclerosis and eburnation of subchondral bone; and the formation of osteophytes and subchondral cysts. When clinically evident, OA is characterized by joint pain, tenderness, limitation of movement, crepitus, occasional effusion, and variable degrees of local inflammation .

OA occurs in all mammalian species and is the earliest documented human disease. Human skeletons from 2 million years ago show evidence of the effect of OA, at the time that bipedality occurred in the evolutionary change from hominids to humans . The bipedal posture promotes OA changes in joints such as the aging lumbar spine and knees.

A. E. Garrod described OA as a clinical entity in 1907 and differentiated it from rheumatoid arthritis (RA). RA was noted to be inflammatory and erosive, whereas OA was a degenerative process with hypertrophic bone features.

I. Disease classification

Primary
1. Localized osteoarthritis. Heberden's nodes 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.
2. Generalized osteoarthritis was named by Moore in 1952. Generalized OA is defined by involvement of three or more joints or joint groups [e.g., the distal interphalangeal (DIP) joints are counted as one group ]. By definition, conditions that are known to produce secondary generalized OA, such as ochronosis, are excluded. The DIP, proximal interphalangeal (PIP), first carpometacarpal (CMC), spine, knee, and hip joints are commonly involved. Other 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 generalized OA patients .
3. Erosive osteoarthritis, 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 characterized by severe disease. DIP and PIP joints of the hands are affected. Results of the test for rheumatoid factor (RF) are negative. Joint radiographs reveal both osteophytes and erosions. In one series, 15% of patients with erosive OA subsequently fulfilled criteria for a diagnosis of RA.
Secondary. See section III.B for causes.

II. Epidemiology. 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 about 20 years to be expressed ; therefore, the majority of patients are over the age of 60. OA results in 68 million lost work days per year and 4 million hospitalizations per year. About 100,000 patients in the United States are unable to walk from bed to bathroom because of OA. OA of the knee is the second leading cause of disability in the elderly, following heart disease.

An interesting epidemiologic clue from the work of Nevitt et al. suggests that women who are long- term users of estrogen replacement therapy have decreased rates of OA of the hip, which adds support to the role of bone in the expression of this disease. This line of evidence is also consistent with findings of regional abnormalities of bone density and vascularity in periarticular densitometry studies and scintigraphy studies. Finally, epidemiologic studies suggest that low levels of vitamin D may be related to the progression of OA of the knee.

Radiographic surveys reveal that the majority of subjects over age 55 have radiographically confirmed disease. It is further estimated that 90% of people over age 70 have radiographic evidence of OA in at least one joint. Above age 55, women are affected more than men. Between the ages of 40 and 55, there is little difference in male versus female prevalence. Studies of ethnic groups in the United States reveal that African-American women are more likely to get knee OA than are Caucasians.

III. Pathogenesis

Primary osteoarthritis. 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 2 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.
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:
1. Aging. The ability of articular cartilage to withstand fatigue testing diminishes progressively with age. However, no specific biochemical defect of aging cartilage has yet been identified. It is also of interest that in human cartilage, chondrocytes remain normal in number and metabolic activity as the tissue ages.
2. Mechanical factors (wear and tear). Accumulated microtrauma causes changes in subchondral bone that likely affect the ability of a joint to absorb the force of impulse loading, thus 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.
3. 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. Primary OA in the form of Heberden's nodes also points to the importance of a genetic factor in pathogenesis. Polymorphisms of the type 2 collagen gene have recently been identified in a family with premature OA.
4. Biochemical factors. The principal early change in OA cartilage is a decreased content of PGs. (Collagen content remains 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 matrix metalloproteinase activity.
Secondary osteoarthritis. Disorders that damage joint surfaces and cause cartilage changes characteristic of OA are as follows :
1. Mechanical incongruity of the joint
  1. Congenital and developmental disorders, such as hip dysplasia, slipped femoral capital epiphysis, and multiple epiphyseal dysplasia.
  2. Prior joint trauma.
  3. Prior joint surgery, such as meniscectomy.
2. Prior inflammatory joint disease, such as RA or infectious arthritis.
3. Prior bone disease, such as Paget's disease or osteonecrosis.
4. 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. Large cystic areas and evidence of osteonecrosis may be seen on radiographs.
5. Neuropathic joint disease. Loss of pain or proprioception 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 severe OA changes with loss of cartilage, exuberant osteophyte formation, bizarre bony overgrowth, fragmentation of subchondral bone with pathologic fractures, and eventually disintegration of the joint structure.
6. Excessive intraarticular steroid injections may be associated with OA. Two mechanisms are postulated:
  1. Intraarticular injection relieves pain and thereby allows overuse of an already damaged joint, and
  2. Cartilage may be directly damaged by injected steroids.
7. Endocrinopathies and metabolic disorders (see also Chapter 48).
  1. Acromegaly.
  2. Cushing's disease and long-term corticosteroid therapy via the mechanism of osteonecrosis. Corticosteroids inhibit osteoblast function and cause a secondary hyperparathyroidism, which activates osteoclasts and so accelerates subchondral bone damage.
  3. 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 Milwaukee shoulder syndrome.
  4. Gout.
  5. 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 disks is characteristic.
  6. Wilson's disease. Premature OA, pseudogout, and chondromalacia patellae are articular manifestations of this disorder of copper metabolism.
  7. 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.

IV. Pathology. Various features are seen in cartilage and bone as the disease progresses.

Structural breakdown of cartilage. In order of progression, this process consists of the following:
1. Fibrillation and fissuring.
2. Focal and diffuse erosions of the cartilage surface.
3. Thinning and complete denudation of cartilage.
Changes in subchondral bone
1. Subchondral bony sclerosis.
2. Cyst formation.
3. Bone thickening with eburnation.
4. Reactive proliferation of new bone and cartilage at the joint periphery to produce osteophytes. Buckland-Wright has shown that bony changes of subchondral cortical sclerosis and osteophytosis precede changes in articular cartilage, measured radiographically as a loss in joint space width.
Other changes. Some mild degree of synovitis can be expected, perhaps a consequence of attempts to remove degenerative bone and cartilage debris from the synovial space. Additional changes include degeneration of menisci and periarticular muscle atrophy.

V. General clinical presentation

History
1. Symptoms
  1. Symptomatic patients are usually over the age of 40. It should be noted that radiographic OA without clinical symptoms is quite common.
  2. Patients complain of pain of insidious onset in one or a few joints. The pain is aching and poorly localized.
  3. Pain first occurs after normal joint use and can be relieved by rest. As the disease progresses, pain during rest develops. Morning joint stiffness lasts less than half an hour .
  4. Systemic symptoms are absent.
2. The most common sites of involvement are the DIP and first CMC joints of the hand and the first metatarsophalangeal (MTP) joint in the foot ; 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 presses, pain is more common as a result of pathology in bone, which is richly innervated. Later-stage disease is characterized by osteophytes and radiographic joint space narrowing, particularly in large, weight-bearing joints such as the knee and hip.
Physical examination
1. Joints may be tender, especially if swelling and warmth (synovitis) are present. However, tenderness may be present without signs of inflammation. Pain with weight bearing may be present without pain on passive range of motion. Joint enlargement may result from the presence of effusion, synovial hyperplasia, or osteophytes.
2. In later disease stages, there may be crepitus, gross deformity, and subluxation (caused by cartilage loss, collapse of subchondral bone, bone cysts, and gross bony overgrowth).
3. Limitation of motion increases as disease progresses, perhaps caused by joint surface incongruity, muscle spasms and contracture, capsule contracture, or mechanical blockage by osteophytes or loose bodies.
Radiographic findings. Radiographs are not needed in the majority of clinical situations and can be reserved for situations of persistent unexplained joint symptoms. However, when a radiographic film is obtained, one must be aware that OA is very common and not overlook other arthritides or fractures when evaluating a painful joint. Special views may be needed to evaluate the extent of involvement of a particular joint.
1. Radiographic criteria for OA are as follows:
  1. Joint space narrowing secondary to degeneration and disappearance of articular cartilage. Precise measurement of joint space narrowing is not available for routine clinical use but is currently used in research studies directed at testing disease-modifying therapies in knee OA.
  2. Osteophyte formation at joint margins or sites of ligamentous attachment.
  3. Subchondral bone sclerosis.
  4. Subchondral bone cysts.
  5. Altered shape of a bone end caused by bone remodeling.
Other imaging modalities. Scintigraphy has been shown to predict the progression of OA in some studies but is rarely used in routine practice. It is difficult to view the bone component of the joint organ with magnetic resonance imaging (MRI), but MRI can help to define ligament or meniscus abnormalities.
Laboratory studies
1. No specific or diagnostic abnormalities are seen in primary OA. No cartilage or bone markers of disease progress have been validated .
2. Blood and urine. Because of the localized nature of OA and the absence of systemic manifestations, clinical laboratory testing is usually not necessary to manage the patient. Values for the erythrocyte sedimentation rate, complete blood cell count, RF, chemistry studies, and urinalysis are generally normal. They are helpful in evaluating associated conditions and causes of secondary OA and in excluding other causes of arthritis. It should be kept in mind that low titers of RF are a common false-positive finding in the elderly.
3. Synovial fluid, when present, is usually noninflammatory, with fewer than 2,000 ( mainly mononuclear) white blood cells per microliter.

VI. Specific patterns of joint disease

Hands
1. History. DIP joints are the most frequent site of hand involvement in OA, and PIP joints are also affected. The first CMC joint may be involved and be quite symptomatic, especially in patients whose occupations require repetitive use of this joint.
2. Physical examination. In patients with Heberden's (DIP) or Bouchard's (PIP) nodes, swellings over the joint are present, and the range of motion is decreased. The nodes are usually not tender. In some patients, small gelatinous cysts occur on the dorsal aspect of the DIP joints; they seem to be attached to tendon sheaths, resemble ganglia, and usually precede the development of Heberden's nodes. When the first CMC joint is affected, range of motion becomes limited, and a tender prominence develops at the base of the first metacarpal bone, which may lead to a squared-off" appearance of the hand.
3. Radiographs. Because the physical signs of hand OA are so characteristic, hand radiographs are rarely needed. Patients with mild radiographic changes usually have no symptoms. Images of Heberden's nodes show joint space narrowing, subchondral sclerosis, cysts, and spurs. Although nodes may feel hard and bonelike, they may not be radiodense. When the first CMC joint is involved, subluxation of the base of the first metacarpal bone may be noted.
Hips
1. History. As a result of the key role of the hip in locomotion, patients with OA of the hip may be significantly disabled. Patients are usually older than those with hand involvement. Men are more often affected than women. In 20% of patients with unilateral disease, contralateral disease will develop within 8 years. Patients often complain of pain that increases with motion and weight bearing and decreases with rest. They may also complain of stiffness and a limp.
  Hip pain is usually felt on the outer aspect of the groin or inner thigh. Pain that originates in the hip may sometimes be perceived as originating in the medial knee or distal thigh (20% of patients), buttocks, or sciatic region. Patients may walk with an antalgic (pain-avoiding) gait, which may alter the gait pattern and cause pain in other joints of the lower extremities or the back. Sitting or rising may be especially difficult for these patients. It is important to distinguish true hip pain from pain caused by a lumbar radiculopathy, femoral hernia , or vascular insufficiency.
2. Physical examination. Decreased range of motion and pain on motion are the primary findings. Internal rotation is affected first. As deterioration progresses, there is further loss of rotation and loss of extension, abduction, and flexion. Joint contractures may develop. In the early stages of OA, flexion may not cause pain; however, extension and rotation will. In cases in which the radiation of the pain is atypical (to the knee), symptoms attributed to the hip can be reproduced by moving the hip through the extremes of motion while fixing all motion of the knee. Shortening of the limb caused by contracture or progressive lateral and upward subluxation of the femoral head may be observed. Compensatory lordosis of spine may also be observed secondary to flexion contracture of the hip.
3. Radiographs. Compared with OA symptoms in other joints, hip symptoms correlate better with radiographic findings. Virtually all patients with severe radiographic findings will have complaints attributable to the hip. Anteroposterior views of the pelvis should be obtained routinely when OA of the hips is suspected; these will provide information about the hips, sacroiliac joints, and pelvic bones. Advanced cases of hip OA may show protrusion acetabuli.
4. Associated and predisposing conditions. Some authors feel that OA of the hip is usually secondary to a developmental abnormality.
  1. Congenital dysplasia of the hip may account for 25% of OA cases in older Caucasian patients. The acetabulum does not develop properly and is shallow , which often results in femoral head subluxation and secondary degenerative changes. Patients may present with a limp in childhood or with premature OA in adulthood .
  2. Slipped capital femoral epiphysis. Just before the femoral epiphysis closes (between ages 16 and 19), the femoral head may be displaced posteromedially. These patients may present with a painful limp in adolescence or early adulthood.
  3. Legg-Calv -Perthes disease is idiopathic osteonecrosis of the proximal femoral capital epiphysis, which occurs in young (3 to 8 years old) boys. The osteonecrosis often results in an abnormally large, flat femoral head with a wide, short neck.
Knees
1. History. The knee is frequently affected by OA. Even with normal walking, about four times the body weight is transmitted through the knee joint. Patients complain of trouble with kneeling, climbing stairs, and getting in and out of chairs. Locking of the knee may result from loose joint bodies. Morning stiffness is common but usually lasts less than 30 minutes.
2. Physical examination. Tenderness may be present along the joint line. Osteophytes may be palpated as irregular bony masses. Crepitus may be felt with the examiner 's hand held over the patella during knee motion. Quadriceps atrophy may be present.
  1. Medial and lateral compartment disease. The medial compartment is the most frequently affected of the three knee compartments. Genu varus commonly occurs with medial compartment disease. Genu valgus, although less common, may occur when the lateral compartment is involved.
    The joint may be unstable as a result of cartilage loss and secondary lengthening of the collateral ligaments. It is important to compare the degrees of varus valgus deformity (of the extended knee) with and without weight bearing. If a change into varus alignment or an increase in the degree of deformity occurs with weight bearing, it is evidence of cartilage loss and compartment deformity rather than of ligamentous laxity alone.
  2. Patellofemoral disease. With patellofemoral OA, the patella loses side-to-side mobility, which results in a loss of about 10% of extension and flexion. Pain and tenderness are most marked anteriorly. Pain may be elicited if the patella is held firmly against the femur and the quadriceps is isometrically contracted. Patellofemoral disease may occur alone without medial or lateral compartment disease.
3. Radiographs
  1. Standard views are the anteroposterior and lateral for most clinical situations. It is important to obtain these films during weight bearing to assess amounts of varus-valgus deformity and joint space narrowing. Standing films, with about 6 degrees of knee flexion, show the femoral cartilage and tibial plateau cartilage in direct contact and demonstrate joint space narrowing more reliably than non “weight-bearing films. Osteophytes and subchondral bone sclerosis and cyst formation are observed as OA progresses.
  2. A tunnel view is obtained with the knee in slight flexion to expose the intercondylar notch . This view allows evaluation of loose bodies, intraarticular spurs, and changes in the tibial intracondylar spines.
  3. The orientation of a sunrise view is tangential to the flexed knee; this view allows evaluation of the patellofemoral articulation.
4. Associated and predisposing conditions
  1. Fractures of the tibial plateau or femoral condyles with mechanical incongruence .
  2. Ligamentous injuries causing instability.
  3. Chronic patellar dislocation.
  4. Severe varus and valgus deformities.
  5. Internal derangement. Torn menisci predispose to OA, as do absent menisci after meniscectomy.
  6. Osteonecrosis (see Chapter 45).
  7. Chondromalacia patellae is a degeneration of the patellar cartilage most prominent in the age group of 15 to 30 years. There is pain during activity, especially descending stairs. Pain is elicited when the patella is pressed into the femoral groove as the patient tightens the quadriceps muscle.
Spine. Degenerative disease of the spine may be categorized as osteoarthritis or spondylosis. Because the posterior apophyseal joints are true diarthrodial joints, they may undergo the usual changes of OA, including joint space narrowing, sclerosis, and spur formation. The degenerative changes that affect the disks and vertebral bodies are properly referred to as spondylosis. Disks may herniate and compress the spinal cord or nerve roots. Degenerative changes of the vertebral bodies result in osteophytes that may cause mechanical compression of vital structures (spinal cord, nerve root, and, rarely, vessels).
1. History
  1. Local pain and stiffness may be caused by paraspinal ligament involvement or paraspinal muscle spasm.
  2. Radicular symptoms occur at all spinal levels, but are more common in the lumbar area and in the C5 “6 and C6 “7 roots.
    1. Involvement of the cervical spine is usually seen at a neural foramen, secondary to impingement by osteophytes. Radicular symptoms tend to occur in the cervical spine because neural foramina and the spinal canal are relatively small in this area. Symptoms include neck pain that often radiates to the shoulder, upper back, and more distal aspects of the upper extremity . Weakness and paresthesias of the hand and arm may also occur.
    2. Lumbar spine. Patients complain of low back pain that often radiates down the buttocks and may even extend into the legs and feet. The pain may increase with coughing and straining. With severe lesions, motor and sensory abnormalities may be present. A cauda equina syndrome with sphincter dysfunction can also develop (see Chapter 18.)
  3. Cord compression by intervertebral ridges at cervical and thoracic levels may result in progressive myelopathy with minimal or no radicular pain.
  4. Mechanical compression of vital structures also occurs mostly at the level of the cervical spine. Large anterior spurs may cause dysphagia, hoarseness, or cough. Compression of vertebral arteries may produce symptoms of vertebrobasilar insufficiency with vertigo, double vision, scotomas, headache , or ataxia. These symptoms often vary with head and neck position. Compression of the anterior spinal artery may produce a central cord syndrome.
2. Physical examination. The spinal examination may reveal decreased range of motion and local tenderness. A careful neurologic evaluation to detect absent reflexes, long- tract signs, and a radicular pattern of weakness and sensory abnormalities is important.
3. Radiographs. Severe degenerative changes may be present on radiographs with few symptoms. In contrast, a small spur that is critically placed may cause significant morbidity. Oblique films must be ordered to evaluate neural foramina. Standard anteroposterior and lateral views will not demonstrate impingement by a bone spur or a subluxation of an apophyseal joint. Osteophytes usually arise from the anterior and anterolateral aspects of vertebral bodies and are best seen on lateral films. A decrease in the intervertebral disk space secondary to disk degeneration is seen most often in the lower cervical and lumbar spine. A vacuum phenomenon indicative of disintegration of the nucleus pulposus of the disk may also be present. Anterior vertebral wedging may be seen. Specialized imaging methods such as computed tomography (CT) and MRI are useful for further selective investigations. CT may be of value in defining a bony cause of neurologic compression symptoms. MRI is useful to study soft-tissue structures of the neck, such as disks, when clinical examination and plain radiographs do not yield the diagnosis.
  In summary, advanced imaging techniques are best reserved for those clinical situations in which standard initial therapy has failed, or in which neurologic signs or symptoms are progressive.
Feet
1. History. The first MTP joint is one of the most common sites of OA involvement. Acute swelling and pain may be caused by bursal inflammation at the medial side of the metatarsal head (bunion). Patients often have a history of using improper footwear. In contrast, OA of the ankle or tarsal joints is rare and, when present, is usually secondary to trauma or to a systemic disease such as hemochromatosis.
2. Physical examination may reveal tenderness over the first MTP joint and hallux valgus deformity. The great toe is unable to bear weight normally, and added stress is placed on the metatarsal heads.
3. Radiographs. Typical changes of OA, such as sclerosis, joint space narrowing, and osteophyte formation, may be seen at the first MTP joint. Subluxation of the great toe with hallux valgus deformity may be noted. Radiographic changes in the midtarsal joints are common; however, they are infrequently associated with symptoms.
Temporomandibular joint. Crepitus, tenderness, and pain (often referred to the ear) are common problems that are sometimes attributed to dental malocclusion. Radiographic characterization of this joint is difficult. MRI can be utilized when more extensive imaging is indicated.

VII. Differential diagnosis. Primary OA can be confused with other forms of arthritis because it may occasionally present as an inflammatory polyarthritis of the hands or as monarticular arthritis. In addition, radiographic evidence of OA is so common that its presence may be unrelated to the true etiology of the patient's complaints. (See Chapter 14,Chapter 15,Chapter 16,Chapter 17,Chapter 18,Chapter 19,Chapter 20 and Chapter 21, which discuss diseases in specific anatomic regions .)

Rheumatoid arthritis
1. Monarticular rheumatoid arthritis. When RA presents as monarticular arthritis of a large joint, differentiation from OA may be difficult and is based on the following:
  1. Synovial fluid analysis. RA fluid contains more white blood cells (>5,000) with a higher percentage of neutrophils, and has poorer viscosity than OA fluid.
  2. Radiographs in patients with RA usually show erosions and juxtaarticular osteoporosis, although the findings are often normal in early RA. Osteophytes, subchondral bone cysts, and sclerosis suggest OA. However, Heberden's nodes and other degenerative abnormalities may coexist with RA.
  3. Blood studies. The erythrocyte sedimentation rate is often elevated, and RF is usually present in RA.
  4. Follow-up observations may eventually reveal a pattern of erosive joint destruction typical of RA. It may take as long as 2 years before the clinical picture is clear.
2. Polyarticular rheumatoid arthritis
  1. Distribution of joint involvement is important when differentiating RA from inflammatory erosive OA.
    1. Rheumatoid arthritis. MCP and PIP and wrist involvement.
    2. Osteoarthritis. DIP and PIP and first CMC joints characteristically affected.
  2. Radiographic features. See section V.C.
  3. Distinguishing clinical features of rheumatoid arthritis
    1. More inflammation with greater loss of joint function.
    2. Involvement of a greater number of joints and in a symmetric fashion.
    3. Quicker progression.
    4. Less knee involvement.
    5. More hand involvement.
    6. Morning stiffness lasting longer than 30 minutes.
    7. Significant systemic symptoms.
Seronegative spondyloarthropathies. These inflammatory diseases frequently involve the interphalangeal joints, single large joints, and the spine. Differentiating features are the following:
1. Psoriasis. Skin and nail lesions and typical patterns of psoriatic arthropathy affecting interphalangeal joints (see Chapter 11 and Chapter 35).
2. Reiter's syndrome. Presence of conjunctivitis, urethritis, and characteristic skin lesions (see Chapter 36).
3. Inflammatory bowel disease. Complaints referable to large or small intestine (see Chapter 34).
4. Ankylosing spondylitis. Sacroiliitis and fine, symmetric, marginal syndesmophytes (see Chapter 33).
Crystal-induced arthritis
1. Gout affects primarily the first MTP joint in addition to other joints of the foot and lower extremity. Tophaceous deposits over the small joints of the hand may be confused with osteophytes. The diagnosis of gout is confirmed by the identification of urate crystals in the joint fluid (see Chapter 37).
2. Calcium pyrophosphate dihydrate arthritis (pseudogout) may coexist with OA. The wrist, shoulder, knee, and ankle joints are commonly involved. Radiographs reveal chondrocalcinosis in most pseudogout patients. The diagnosis is confirmed by identifying birefringent, rhomboidal CPPD crystals in the joint fluid (see Chapter 38). Another type of crystal, basic calcium phosphate, is implicated in the pathogenesis of the destructive OA variant known as Milwaukee shoulder syndrome.
Other disorders that may coexist with OA but are important to identify and treat include the following:
1. Infectious arthritis.
2. Neoplastic synovitis. Lymphoma or leukemia may sometimes be identified by synovial fluid cytology.
3. Pigmented villonodular synovitis. The joint effusion is usually bloody. Diagnosis is confirmed by synovial biopsy.
4. Neoplastic metastasis to juxtaarticular bone. Bone scan is a useful diagnostic measure.
5. Periarticular tendinitis or bursitis.

VIII. Treatment. The American College of Rheumatology has published guidelines for the management of hip and knee OA; these are listed in the references. Therapy directed at other joints follows similar principles.

Nonpharmacologic therapy. Correction of predisposing factors should optimally take place before anatomic changes occur. Weight reduction in the obese patient is a particularly important intervention. Valgus-varus knee deformity and eversion-inversion ankle deformity may require surgical correction.
1. Patient education and self-management programs. Participation in Arthritis Foundation (1-800-283-7800) activities provides patients with a reliable flow of practical information.
2. Joint rest. Excessive use of an involved joint may increase symptoms and accelerate degenerative changes. It is important to protect joints. Weight-bearing joints may be unloaded by use of a cane (held in the hand opposite to the involved extremity and extended in tandem with it), crutches, or a walker. A neck collar may be useful for cervical OA. A first CMC joint splint can be quite helpful in a flare of CMC joint pain.
3. Physical therapy helps to relieve pain and stiffness, recover and maintain joint mobility, and strengthen supporting muscles . It is particularly helpful in patients with hip, knee, low back, and neck disease.
  1. Therapeutic exercise. See Chapter 56. The goal is to preserve range of motion and muscle strength.
  2. Heat therapy generally relieves pain and muscle spasm. Many methods are available, including diathermy and ultrasound (for deep pain), infrared, hot packs , warm bath or shower, and paraffin bath (for hands). See Chapter 56 for regimens.
4. Occupational therapy helps patients to adapt to their disabilities and helps minimize the stress placed on involved joints during activities of daily living (see Chapter 57).
Pharmacologic therapy
1. Analgesics.
  1. Oral. Acetaminophen is a standard baseline therapy. If sufficient analgesic effect is obtained, it avoids the gastric side effects of nonsteroidal antiinflammatory drugs (NSAIDs). The dosage of acetaminophen is 500 to 1,000 mg every 6 hours as required. Concurrent alcohol use should be avoided, and liver disease is a contraindication to use.
  2. Topical. Capsaicin cream (available in 0.025% and 0.075% strengths) is derived from the pepper plant and relieves pain via local reductions of substance P. It is applied three or four times per day to the affected area. Care must be taken to avoid contact with the eyes. It may take 2 weeks to obtain a therapeutic effect, so it is customary to use an oral medication during this period. The analgesic effects of acetaminophen and topical capsaicin are synergistic, and this is a particularly useful combination in the elderly.
2. Nonsteroidal antiinflammatory drugs. The choice of an NSAID should take into account such factors as efficacy, cost, adverse reactions, compliance, comorbidities, and past treatment. If NSAIDs are indicated after failure of the treatment modalities described above, they should be first used at low doses and on an as-needed basis if possible to minimize adverse reactions , especially in the elderly. The elderly are especially prone to peptic ulceration and unpredictable bleeding; these are clinically more serious than in young patients, who tend to have more physiologic reserve and are less likely to suffer from multiple diseases and be taking multiple medications that can further exacerbate a gastrointestinal insult. In addition, the aging process leads to a slow decrease in renal function that in turn makes elderly patients more susceptible to the renal adverse actions of NSAIDs, as detailed below.
  1. Adverse reactions to the NSAIDs include peptic ulcer in about 2%, rash in 2%, central nervous system effects such as tinnitus, and idiosyncratic hepatitis (rare). Dyspepsia is a frequent reason for NSAID discontinuation. Renal reactions, listed in order of decreasing frequency, are edema, transient acute renal insufficiency, tubulointerstitial nephropathy, hyperkalemia, and renal papillary necrosis.
  2. Choice of nonsteroidal antiinflammatory drug. There is no evidence that one NSAID class is superior in efficacy to other classes. However, the first cyclooxygenase-2 (COX-2) inhibitor drug, which entered the U.S. market in February 1999, causes less gastrointestinal injury than do standard NSAIDs. It is reasonable to try a drug for 3 to 4 weeks, stop it if there is no therapeutic benefit, and then select another NSAID from a different structural class. Prescribing information for each drug listed below can be found in Appendix E.
    1. Cyclooxygenase-2 inhibitors . Celecoxib, the first drug in this new class of NSAIDs, selectively inhibits the isoenzyme COX-2. This results in suppression of inflammation without disruption of the gastrointestinal protective effect of the COX-1 isoenzyme. In addition, celecoxib has no effect on platelet aggregation or bleeding time. The dose for osteoarthritis is 200 mg daily or 100 mg twice daily without regard to food. A second COX-2 medication, rofecoxib, was also approved by regulatory authorities in 1999. The dosage for OA is 12.5 to 25 mg once daily. The full safety picture for new drugs is typically clearer after they have been on the market for 2 to 3 years and used in larger populations. At that time, rarer adverse reactions have been detected and additional postmarketing studies have been completed.
    2. Acetic acids. Sulindac is reputed to be associated with a lower rate of renal adverse reactions than other NSAIDs. It is supplied as 150-mg and 200-mg tablets. The dosage is 150 to 200 mg twice daily. Other members of this chemical family are indomethacin and tolmetin. Indomethacin is a potent analgesic but is not indicated for OA because it is poorly tolerated in the elderly.
    3. Propionic acids. Members of this family include ibuprofen and naproxen. Specific information on these drugs is found in Appendix E. The dose of naproxen is 250 to 500 mg twice daily.
    4. Oxicam. Piroxicam has the advantage of being taken in one daily dose, which assists with compliance. It is supplied as 10-mg and 20-mg capsules. The usual dosage is 20 mg once daily.
    5. Salicylates. Aspirin products are less frequently used because of tolerance problems (gastrointestinal tract and central nervous system), particularly in the elderly. Enteric-coated aspirin (Ecotrin) is supplied as 325-mg or 500-mg tablets. The initial dosage is 500 mg four times daily. It should be taken after meals to minimize dyspepsia. Plain aspirin is not recommended for long-term use because it causes more occult blood loss than does Ecotrin. Salsalate is a non-acetylated salicylate that is associated with minimal gastrointestinal toxicity and does not affect platelet function. (Other drugs in this family are choline salicylate, choline magnesium trisalicylate, and diflunisal.) These non-acetylated drugs can be useful in arthritis secondary to bleeding dyscrasias because they have little effect on platelet function. Salsalate is supplied as 500-mg and 750-mg tablets. The usual dosage is 750 to 1,000 mg two to three times daily.
3. Corticosteroids
  1. Systemic. Oral corticosteroids have no role in the treatment of OA.
  2. Intraarticular injections may be of benefit if used judiciously in patients with one or two persistently inflamed joints. A joint should not be injected more than three times a year. Intraarticular corticosteroids can have an adverse effect on local cartilage metabolism; thus, excessive use of this treatment may aggravate OA rather than relieve it. Dosages for specific joints and precautions are listed in Chapter 4.
  3. Intraarticular hyaluronic acid is now available and can provide symptomatic relief lasting for several months when given as a series of injections. It is indicated for OA of the knee. These drugs (Synvisc and Hyalgan) are useful in patients who cannot tolerate NSAIDs or in whom NSAIDs have failed. Synvisc can be given in a series of three injections 1 week apart, versus five injections for Hyalgan.
4. Experimental therapy. At present, there are no therapies that reverse or halt the structural abnormalities of cartilage or bone in OA. Clinical trials are under way directed at cartilage targets and employing agents such as doxycycline and selective matrix metalloproteinase inhibitors. Biologic agents directed at targets such as interleukin-1ra are also being designed.
  In addition, one can expect to see clinical trials directed at bone targets in the future in accord with the joint organ" concept.

IX. Surgical treatment. In addition to traditional surgical procedures and prosthetic joint replacement, a relatively recent advance is transplantation of cartilage in situations in which a focal defect is suitable for repair. Although it is not a routine procedure and is quite costly, cartilage transplantation adds to the tools available to preserve joint function.

Indications
1. Relief of pain or severe disability after failure of conservative measures to halt or alleviate the pathologic process.
2. Correction of a mechanical derangement that may lead to OA.
Contraindications
1. Infection.
2. Poor vascular supply.
3. Emotional instability or occupational factors that make surgical rehabilitation unlikely to succeed.
4. Obesity (relative contraindication).
5. Serious medical illness (relative contraindication).
6. Movement disorders, such as Parkinson's disease, and other neurologic diseases, such as Charcot's joint.
Knee and hip procedures. See Chapter 54 and Chapter 55 for a discussion of surgical therapy, including prosthetic joint replacement. Experienced surgeons obtain excellent functional results with hip and knee replacement surgery. Prostheses can be expected to last 15 years or so.
Arthroscopic examination and removal of loose articular and meniscal debris can relieve pain and improve function. Simple joint irrigation can provide substantial clinical benefit in knees affected by OA.

X. The prognosis of osteoarthritis is highly variable. With DIP involvement of the hand, there is moderate pain and stiffness but little limitation of overall function. Disease of weight-bearing joints is more likely to cause disability. The time between the onset of hip pain and the development of serious disability averages 8 years. OA of the knee carries a worse prognosis than OA of the hip. Varus knee deformity and early onset of pain are poor prognostic signs.

Bibliography

Altman R, et al., and the OARS Task Force (Osteoarthritis Research Society). Design and conduct of clinical trials in patients with osteoarthritis. Osteoarthritis Cartilage 1996;4:217.

Buckland-Wright JC. Quantitative microfocal radiographic assessment of osteoarthritis of the knee from weight bearing tunnel and semiflexed standing views. J Rheumatol 1994;21:1734.

Buckland-Wright JC, et al. Accuracy and precision of joint space width measurements in standard and macroradiographs of osteoarthritic knees. Ann Rheum Dis 1995;54:872.

Dieppe PA, et al. Bone scintigraphy predicts the progression of joint space narrowing in osteoarthritis of the knees. Ann Rheum Dis 1993;52:557.

Hochberg MD, et al. Guidelines for the medical management of osteoarthritis. Part I. Osteoarthritis of the hip. Part II. Osteoarthritis of the knee. Arthritis Rheum 1995;38:1535,1541.

Lawrence RC, et al. Estimates of the prevalence of arthritis and selected musculoskeletal disorders in the United States. Arthritis Rheum 1998;41:778.

McAlindon TE, et al. Relation of dietary intake and serum levels of vitamin D to progression of osteoarthritis of the knee among participants in the Framingham study. Ann Intern Med 1996;125:353.

Nevitt MC, et al. Association of estrogen replacement therapy with the risk of osteoarthritis of the hip in elderly white women. Arch Intern Med 1996;156:2073.

Radin EL, Paul IL. Does cartilage compliance reduce skeletal impact loads? The relative force-attenuating properties of articular cartilage, synovial fluid, periarticular soft tissues and bone. Arthritis Rheum 1970;13:139.

Towheed TE, Hochberg MC. A systematic review of randomized controlled trials of pharmacologic therapy in osteoarthritis of the knee. Semin Arthritis Rheum 1997;26:755.

Westacott CI, et al. Alteration of cartilage metabolism by cells from osteoarthritic bone. Arthritis Rheum 1997;40:1282.

Books@Ovid
Copyright 2000 by Lippincott Williams & Wilkins
Stephen A. Paget, M.D., Allan Gibofsky, M.D., J.D. and John F. Beary, III, M.D.
Manual of Rheumatology and Outpatient Orthopedic Disorders

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