OSTEOARTHRITIS

Osteoarthritis (OA) is the most common joint disease, affecting nearly 50% of those over 65 years of age and almost all individuals over age 75. OA affects primarily the weight-bearing joints of the axial and peripheral skeleton, causing pain, limitation of motion, deformity, progressive disability, and decreased quality of life.1−5 Other names for OA include degenerative joint disease and hypertrophic arthritis, but these terms have shortcomings. OA implies lack of inflammation and excess materials in the joint, degenerative joint disease suggests a wearing out of the joint, and hypertrophic arthritis describes the

overgrowth of bone and cartilage that is only one aspect of OA. Thus the term “osteoarthritis” best reflects the degenerative changes that occur in the metabolically active cartilage and bone within a joint. OA is characterized by increased destruction of cartilage and subsequent proliferation of adjacent bone. The regenerated articular surfaces do not possess the same qualities and architecture as the original joint, and this change in structure leads to pain, decreased or altered motion, crepitus, and possibly local inflammation.2 The pain of OA typically worsens with use and improves with rest. Morning stiffness lasting less than 1 hour and “gelling” of the joints after inactivity are also common. The inflammation associated with OA is usually mild or localized, in contrast to that of rheumatoid arthritis or other inflammatory diseases affecting the joints.

EPIDEMIOLOGY:

PREVALENCE BY AGE, SEX, AND RACE

Based on prevalence data from the National Centers for Health Statistics, an estimated 15.8 million adults, or 12% of those between 25 and 74 years of age, have signs and symptoms of OA.4 The prevalence of OA increases with age. In those under age 45, about one-fifth have OA of the hands, while for those aged 75 to 79 years, 85% have OA of the hands. OA of the knee occurs in less than 0.1% of those aged 25 to 34 years, but in 10% to 20% of those aged 65 to 74 years. The overall incidence of hip or knee OA is approximately 200 per 100,000 person-years. The incidence of hip OA is greater in women than in men, whereas the rate for knee OA is similar between genders. In men, rates of knee and hip OA increase with age, but in women

rates remain stable.

ETIOLOGY:

OBESITY

Increased body weight is strongly associated with hip, knee, and hand OA.3,12,13 Obesity often precedes OA and contributes to its development, rather than occurring as a result of inactivity from joint pain. In a three-decade Framingham Study, the highest quintile of body mass was associated with a higher relative risk of knee OA (relative risk of 1.5 to 1.9 for men and 2.1 to 3.2 for women).

OCCUPATION, SPORTS, AND TRAUMA

Those participating in activities involving repetitive motion or injury are at increased risk for developing OA.14 Workers exposed to repetitive stress of the hands or lower limbs are at higher risk for OA of the stressed joints. Lower-extremity OA in some professional sports is also increased, likely secondary to repetitive motion, trauma to the joint, loss of ligament integrity, or damage to the meniscus. Risk for OA depends on the type and intensity of physical activity. The Framingham Study showed that heavy physical activity increases knee OA risk, especially in the obese, whereas moderate or light activity does not.15

GENETIC FACTORS

Heredity plays a role in osteoarthritis.3,17 Heberden’s nodes are 10 times more prevalent inwomen than in men, with a twofold higher risk if the woman’s mother had them. Genetic links also have been shown with OA of the first metatarsophalangeal joint and with generalized OA. Premature development of OA is associated with a defect in type II procollagen.

OSTEOPOROSIS

An inverse correlation betweenOAand osteoporosis has been demonstrated, and both men and women with OA have increased bone mineral density at numerous skeletal sites.2,18 This relationship may derive from the influence of body weight on both diseases, because heavy individuals have higher bone density as well as increased risk of OA.

PATHOPHYSIOLOGYOPHYSIOLOGY

 OA falls into two major etiologic classes. Primary (idiopathic) OA, the mostcommontype, has no identifiable cause. Subclasses

of primary OA are localized OA, involving one or two sites, and generalized OA, affecting three or more sites. Erosive osteoarthritis is used to describe the presence of erosion and marked proliferation in the proximal and distal interphalangeal joints of the hands. Secondary OA is that associated with a known cause such as rheumatoid or another inflammatory arthritis, trauma, metabolic or endocrine disorders, and congenital factors (Table 90–1).2,19−21 To aid uniform reporting of rheumatic diseases, a classification scheme and criteria for OA of the hip, knee, and hand were devised by the American College of Rheumatology (ACR). Criteria include the presence of pain, bony changes on examination, a normal erythrocyte

sedimentation rate, and characteristic radiographs.1,2,22 For hip OA, a patient must have hip pain plus two of the following: an erythrocyte sedimentation rate of less than 20 mm/h, radiographic femoral or acetabular osteophytes, or radiographic joint space narrowing. For knee OA, a patient must have knee pain and radiographic osteophytes plus one of the following: age greater than 50 years, morning stiffness of 30 minutes’ or less duration, or crepitus on motion. Improved understanding of articular cartilage physiology has transcended the wear-and-tear theory of OA. Some changes in the OA joint may reflect compensatory processes to maintain function in the face of ongoing joint destruction. As such, the pathogenesis of OA involves not only biomechanical forces, but also inflammatory, biochemical, and immunologic factors.19−21,23−26 To understand the pathophysiology of OA, familiarity with the normal joint is essential. To this end, a review of the biochemistry and function of normal cartilage and of the diarthrodial joint is provided.

CLASSIFICATION OF OA

Primary (Idiopathic)                                 Secondary

Localized                                           Trauma—acute/chronic

Generalized                                                 Underlying joint disorder

Local (fracture/infection)

Diffuse (rheumatoid arthritis)

Erosive                                                       Systemic metabolic or endocrine disorders

Wilson’s disease

Acromegaly

Hyperparathyroidism

Hemochromatosis

Paget’s disease

Diabetes mellitus

Obesity

Crystal deposition disease

Basic calcium phosphate crystal disease

Calcium pyrophosphate dihydrate

Hydroxyapatite

Other calcium-containing crystals

Monosodium urate monohydrate

Neuropathic disorders

Intra-articular corticosteroid overuse

Avascular necrosis

Bone dysplasia

STRUCTURE AND BIOCHEMICAL COMPOSITION

OF CARTILAGE

Articular cartilage is a hydrated (75% to 80% water), complex extracellular matrix (ECM) with a small number of chondrocytes

(<5%). The remaining 20% to 25% of matrix contains three types of molecules: collagens, large aggregates of proteoglycans, and noncollagenous proteins. Orientation of collagen fibers is critical: superficial fibers are parallel to the surface, reducing friction and allowing forces to be dissipated; basal layer collagen fibers are perpendicular to the surface to anchor cartilage to the calcified zone or subchondral bony end plate. Cartilage undergoes continual biochemical and structural remodeling controlled by chondrocytes, which synthesize collagen and proteoglycans, and also play a role in their degradation. Because adult

articular cartilage is avascular, chondrocytes are nourished by synovial fluid. With the cyclic movement and loading of joints, nutrients flow into the cartilage, whereas immobilization reduces nutrient supply. Recent research has highlighted the role of peptides and proteins regulating chondrocyte function and cartilage metabolism.19−21,23−26 Insulin-like growth factor, epidermal growth factor, fibroblast growth factor, and other agents enhance chondrocyte proliferation and proteoglycan synthesis. By contrast, interleukin-1 and tumor necrosis factor-α promote chondrocyte secretion of matrix metalloproteinases (MMPs), including collagenase (MMP-1) and stromelysin (MMP-2). These proteinases in turn degrade matrix proteins. Interleukin-1 and

tumor necrosis factor-α also suppress proteoglycan and collagen synthesis in the ECM. Biomechanical factors, including load and strain, also affect chondrocyte function, and joint loading increases proteoglycan synthesis. The following sections will review the components of the joint matrix, and the pathologic changes in this matrix leading to OA.

Collagen

Five types of collagen (II, IX, X, XI, and VI) are located in cartilage. Type II collagen accounts for 90% to 95% of the total collagen in articular cartilage.19−21,23−26 Type VI appears to attach chondrocytes to the matrix. Type IX collagen, a proteoglycan, may link matrix molecules together. The cross-linked network of type II collagen fibrils with other ECM proteins provides tensile strength and maintains cartilage volume and shape.

OSTEOARTHRITIC CARTILAGE

BIOCHEMICAL CHANGES

Numerous compositional differences have been noted between cartilage in OA and normal individuals (Table 90–2).19−21,23−26 Early in OA, cartilage water content increases, possibly as a result of a damaged collagen network that is unable to constrain PGs, which subsequently gain water. As osteoarthritis progresses, cartilage PG content decreases, possibly through the action of MMPs. Increased collagen synthesis and altered distribution and diameter of the fibers are seen, but collagen content does not appear to change until severe disease is present. Earlier theories suggested that cartilage was passively eroded in OA, but in fact, there is increased metabolic activity, suggesting a reparative response to damage.19−21,23−26 Despite the increased matrix

synthesis by chondrocytes, there is a net loss of PG, as degradation proceeds faster than synthesis. Intense research efforts are directed toward understanding the roles of MMPs and other collagen-degrading enzymes. MMPs are zinc-containing proteinases falling into five related subgroups. MMPs are normally held in check by tissue inhibitors of metalloproteinases

(TIMPs), but there are also substances produced by chondrocytes that activate MMPs.23−26 Imbalance between activators and

inhibitors of MMPs in synovial fluid or local tissues can lead to proteolysis of the ECM, promoting osteoarthritic changes. Recent work showed that cartilage from osteoarthritic human joints exhibited increased collagen-degrading activity colocalized with increased levels of MMP mRNA.24 The subchondral bone adjacent to articular cartilage also undergoes pathologic changes that may precede, coincide with, or follow damage to the articular cartilage. Nevertheless, this damage to subchondral

bone is required and appears to permit continued damage to articular cartilage, leading to progression to OA.25 This subchondral

bone demonstrates increased bone turnover, with both increased osteoclast and osteoblast activity. There is an associated release of vasoactive peptides and matrix metalloproteinases, neovascularization, and subsequent increased permeability of the adjacent cartilage.25,26 This sequence of events leads to continued cartilage degradation, and eventually substantial loss of cartilage, leading to a painful, deformed joint. In summary, the slow progressive changes in OA consist of an increase in water content, loss of PG, and reduction of PG aggregates of cartilage. The cartilage is subsequently unable to repair itself. Alterations in metabolism of subchondral bone adjacent to articular cartilage appear necessary for continued cartilage destruction. Eventually,

progressive loss of articular cartilage and increasing subchondral sclerosis lead to an abnormal and painful joint.

PATHOLOGIC CHANGES

Pathologic changes in bone and cartilage accompany the biochemical changes just described. These changes are noted in both weightbearing and non–weight-bearing joints, and in both primary and secondary OA. A summary of the biochemical changes in cartilage in OA follows.19,20

1. Initial thickening of articular cartilage as ECM is damaged and water content increases

2. Proliferation of chondrocytes and an increase in ECM anabolic and catabolic activity secondary to tissue damage or alterations in ECM structure

3. Decline in response of chondrocytes to stabilize or restore tissue, resulting in progressive cartilage loss

4. Increased turnover of adjacent subchondral bone, leading to release of vasoactive peptides and enzymes, causing cartilage degradation, neovascularization, and increased leakiness of adjacent cartilage, likely contributing to subsequent loss of articular cartilage

5. Fibrillation or splitting of the noncalcified cartilage, likely related to the biochemical changes described

earlier; loss of cartilage exposes the underlying subchondral bone and may lead to microfractures As cartilage is destroyed and the adjacent subchondral bone undergoes pathologic changes, cartilage is eroded completely, leaving denuded subchondral bone to become dense, smooth, and glistening (eburnation). A more brittle, stiffer bone results, with decreased weight-bearing ability and development of sclerosis and microfractures.19,20 Microfractures lead to callus and osteoid production. New bone formations at the joint margins distant from cartilage destruction are referred to as osteophytes, and may be an attempt to stabilize the joint.

Presentation of Osteoarthritis

Age

Usually elderly

Gender

Age <45 more common in men

Age >45 more common in women

Symptoms

Pain

Deep, aching character

Pain on motion

Pain with motion early in disease

Pain with rest late in disease

Stiffness in affected joints

Resolves with motion, recurs with rest

(“gelling” phenomenon)

Usually <30 minutes’ duration

Often related to weather

Limited joint motion

May result in limitations activities

of daily living

Instability of weight-bearing joints

Signs, history, and physical examination

Monarticular or oligoarticular;

asymmetrical involvement

Hands

Distal interphalangeal joints

Heberden’s nodes (osteophytes

or bony enlargements)

Proximal interphalangeal joints

Bouchard’s nodes (osteophytes)

First carpometacarpal joint

Osteophytes give characteristic square

appearance of the hand (shelf sign)

Knees

Patellofemoral compartment involvement

Pain related to climbing stairs

Medial compartment involvement

Genu varum (bowlegged deformity)

Lateral compartment involvement

Genu valgum (knock-knee deformity)

Transient joint effusions

Typically noninflammatory

synovial fluid (WBC <2000/mm3)

Hips

Groin pain during weight-bearing activities

Stiffness, especially after inactivity

Limited joint motion

Spine

L3 and L4 involvement is most common in

the lumbar spine

Signs and symptoms of nerve root compression

Radicular pain

Paresthesias

Loss of reflexes

Muscle weakness associated with

the affected nerve root

Feet

Typically involves the first metatarsophalangeal

joint

Other sites, less commonly involved

Shoulder, elbow, acromioclavicular,

sternoclavicular, and temporomandibular joints

Observation on joint examination

Bony proliferation or occasional synovitis

Local tenderness

Crepitus

Muscle atrophy

Limited motion with passive/active movement

Deformity

Radiologic evaluation

Early mild OA

Radiographic changes often absent

Progression of OA

Joint space narrowing

Subchondral bone sclerosis

Marginal osteophytes

Late OA

Abnormal alignment of joints

Effusions

Characteristics of synovial fluid

High viscosity

Mild leukocytosis (<2000 WBC/mm3)

Laboratory values

No specific test

Erythrocyte sedimentation rate and hematologic

and chemistry survey are normal

PHYSICAL EXAMINATION

Examination of the affected joints reveals tenderness, crepitus, and joint enlargement. Crepitus is a crackling or grating

sound heard with joint movement that is caused by irregularity of joint surfaces. Joint enlargement is related to bony proliferation or to thickening of the synovium and joint capsule. Joint deformity may be present in the later stages of OA as a result of subluxation, collapse of subchondral bone, formation of bone cysts, or bony overgrowth. The presence of a warm, red, tender joint may indicate the presence of an inflammatory arthritis such as gout.

HANDS

Hand OA is associated with pain in specific joints and often with development of bony enlargements (osteophytes). These usually develop slowly and painlessly, appear on lateral and medial aspects of the joint, and are about 10 times more common in women than in men.2,22 Occasionally, these nodes become red, warm, swollen, and painful, usually as a result of trauma or use.

KNEES

The knee is commonly affected in OA. It is important to localize the symptoms because the joint has three separate articulations. Knee OA is associated with pain, tenderness, crepitus, and limited range of motion. Limited joint motion occurs from loss of articular surfaces, muscle spasm, capsular contracture, or mechanical blockage secondary to osteophytes (bony enlargements). Weakness or instability (the joint “gives way”) is frequently noted by patients with knee OA. Such joint instability may lead to decreased activity and muscle atrophy.

HIPS

Hip OA is common in the elderly, with a characteristic presentation. However, pain located on the lateral hip typically represents trochanteric bursitis, while pain in the buttock region may indicate lumbar spine OA or iliopsoas bursitis.

SPINE

Degenerative changes involving the spine may occur in the intervertebral disks, vertebral bodies, or posterior apophyseal articulations. Aside from pain and limitation of motion, nerve root compression is a potential complication of arthritis .

LABORATORY FINDINGS

No specific laboratory abnormalities occur in primary OA.2 If secondary OA is suspected, specific laboratory tests can help identify the cause.

RADIOLOGIC EVALUATION

Radiologic evaluation is an absolute necessity in the diagnosis of OA . Bone erosions and unequivocal radiographic osteopenia are uncommon except in erosive or secondaryOA. Finally, many patients who do not have clinical OA and do not have pain may nonetheless exhibit radiologic changes typical of OA.28 Newer techniques—computed tomography, magnetic resonance imaging, and ultrasound—have been used, but are not suitable for routine use in diagnosing OA.

DIAGNOSIS

The diagnosis of OA is easily made by history, physical examination, and characteristic radiographic findings.2,6,22,28 The major diagnostic goals are (1) to discriminate between primary and secondary OA, and (2) to clarify the joints involved, severity of joint involvement, and response to prior therapies, providing a basis for a treatment plan.

TREATMENT:

Oral analgesics

Acetaminophen, Tramadol

Topical analgesics

Capsaicin 0.025% or 0.075%

Nutritional supplements

Glucosamine sulfate

Nonsteroidal anti-inflammatory drugs

(NSAIDs)