Osteoarthritis Flashcards
Practice Essentials
Osteoarthritis is the most common type of joint disease, affecting more than 30 million individuals in the United States alone. [1] It is the leading cause of chronic disability in older adults, costing the US greater than $185 billion annually.
It can be thought of as a degenerative disorder arising from the biochemical breakdown of articular (hyaline) cartilage in the synovial joints. However, the current view holds that osteoarthritis involves not only the articular cartilage but the entire joint organ, including the subchondral bone and synovium.
Signs and Symptoms
Symptoms of osteoarthritis include the following:
1. Deep, achy joint pain exacerbated by extensive use - The disease’s primary symptom
- Reduced range of motion and crepitus - Frequently present
- Stiffness during rest (gelling) - May develop, with morning joint stiffness usually lasting for less than 30 minutes
Osteoarthritis of the hand
1. Distal interphalangeal (DIP) joints are most often affected
- Proximal interphalangeal (PIP) joints and the carpometacarpal (cmc) joints at the base of the thumb are also typically involved
- Heberden nodes, which represent palpable osteophytes in the DIP joints, are more characteristic in women than in men
- Inflammatory changes are typically absent, less pronounced, or go unnoticed
Diagnosis
Osteoarthritis is typically diagnosed on the basis of clinical and radiographic evidence.
No specific laboratory abnormalities are associated with osteoarthritis.
Background of Osteoarthritis
It has been thought of as a degenerative disorder arising from biochemical breakdown of articular (hyaline) cartilage in the synovial joints. However, the current view holds that osteoarthritis involves not only the articular cartilage but also the entire joint organ, including the subchondral bone and synovium.
Osteoarthritis predominantly involves the weight-bearing joints, including the knees, hips, cervical and lumbosacral spine, and feet. Other commonly affected joints include the distal interphalangeal (DIP), proximal interphalangeal (PIP), and carpometacarpal (CMC) joints.
Although osteoarthritis was previously thought to be caused largely by excessive wear and tear, increasing evidence points to the contributions of abnormal mechanics and inflammation. In addition, some invasive procedures (eg, arthroscopic meniscectomy) can result in rapid progression to osteoarthritis in the knee joint. Therefore, the term degenerative joint disease is no longer appropriate in referring to osteoarthritis.
No specific laboratory abnormalities are associated with osteoarthritis. Rather, it is typically diagnosed on the basis of clinical findings, with or without radiographic studies
Primary and Secondary Osteoarthritis
Historically, osteoarthritis has been divided into primary and secondary forms, though this division is somewhat artificial. Secondary osteoarthritis is conceptually easier to understand: It refers to disease of the synovial joints that results from some predisposing condition that has adversely altered the joint tissues (eg, trauma to articular cartilage or subchondral bone). Secondary osteoarthritis can occur in relatively young individuals
The definition of primary osteoarthritis is more nebulous. Although this form of osteoarthritis is related to the aging process and typically occurs in older individuals, it is, in the broadest sense of the term, an idiopathic phenomenon, occurring in previously intact joints and having no apparent initiating factor.
Some clinicians limit the term primary osteoarthritis to the joints of the hands (specifically, the DIP and PIP joints and the joints at the base of the thumb). Others include the knees, hips, and spine (apophyseal articulations) as well.
As underlying causes of osteoarthritis are discovered, the term primary, or idiopathic, osteoarthritis may become obsolete. For instance, many investigators believe that most cases of primary osteoarthritis of the hip may, in fact, be due to subtle or even unrecognizable congenital or developmental defects.
Treatment Summary
The goals of osteoarthritis treatment include pain alleviation and improvement of functional status.
Nonpharmacologic interventions are the cornerstones of osteoarthritis therapy and include the following:
- Patient education
- Application of heat and cold
- Weight loss
- Exercise
- Physical therapy
- Occupational therapy
- Joint unloading, in certain joints (eg, knee and hip)
Intra-articular pharmacologic therapy includes corticosteroid injection and viscosupplementation, which may provide pain relief and have an anti-inflammatory effect on the affected joint.
Oral pharmacologic therapy begins with acetaminophen for mild or moderate pain without apparent inflammation.
If the clinical response to acetaminophen is not satisfactory or the clinical presentation is inflammatory, consider nonsteroidal anti-inflammatory drugs (NSAIDs). If all other modalities are ineffective and osteotomy is not viable, or if a patient cannot perform his or her daily activities despite maximal therapy, arthroplasty is indicated.
The high prevalence of osteoarthritis entails significant costs to society. Direct costs include clinician visits, medications, therapeutic modalities, and surgical intervention. Indirect costs include such items as time lost from work.
Costs associated with osteoarthritis can be particularly significant for elderly persons, who face potential loss of independence and who may need help with daily living activities.
As the populations of developed nations age over the coming decades, the need for better understanding of osteoarthritis and for improved therapeutic alternatives will continue to grow.
Anatomy of Joints
Joints can be classified in either functional or structural terms.
A functional classification, based on movement, would categorize joints as follows:
- Synarthroses (immovable)
- Amphiarthroses (slightly moveable)
- Diarthroses (freely moveable)
A structural classification would categorize joints as follows:
- Synovial
- Fibrous
- Cartilaginous
Normal synovial joints allow a significant amount of motion along their extremely smooth articular surface. These joints are composed of the following:
- Articular cartilage
- Subchondral bone
- Synovial membrane
- Synovial fluid
- Joint capsule
The Inner physiology of the joint
The normal articular surface of synovial joints consists of articular cartilage (composed of chondrocytes) surrounded by an extracellular matrix that includes various macromolecules, most importantly proteoglycans and collagen. The cartilage facilitates joint function and protects the underlying subchondral bone by distributing large loads, maintaining low contact stresses, and reducing friction at the joint.
Synovial fluid is formed through a serum ultrafiltration process by cells that form the synovial membrane (synoviocytes). Synovial cells also manufacture hyaluronic acid (HA, also known as hyaluronate), a glycosaminoglycan that is the major noncellular component of synovial fluid. Synovial fluid supplies nutrients to the avascular articular cartilage; it also provides the viscosity needed to absorb shock from slow movements, as well as the elasticity required to absorb shock from rapid movements.
Pathophysiology of Osteoarthritis
Primary and secondary osteoarthritis are not separable on a pathologic basis, though bilateral symmetry is often seen in cases of primary osteoarthritis, particularly when the hands are affected.Traditionally, osteoarthritis was thought to affect primarily the articular cartilage of synovial joints; however, pathophysiologic changes are also known to occur in the synovial fluid, as well as in the underlying (subchondral) bone, the overlying joint capsule, and other joint tissues
Although osteoarthritis has been classified as a noninflammatory arthritis, increasing evidence has shown that inflammation occurs as cytokines and metalloproteinases are released into the joint. These agents are involved in the excessive matrix degradation that characterizes cartilage degeneration in osteoarthritis. Therefore, it is no longer appropriate to use the term degenerative joint disease when referring to osteoarthritis.
While there is no cure for osteoarthritis, ongoing research is exploring possible disease-modifying therapies, as in inflammatory arthritis. Recent studies of interleukin-17 (IL-17), a proinflammatory cytokine, have found increased IL-17 levels in the synovium of osteoarthritis joints, as is seen in inflammatory arthritis (ie, rheumatoid arthritis)
Progression of Osteoarthritis
Pathophysiology
In early osteoarthritis, swelling of the cartilage usually occurs, because of the increased synthesis of proteoglycans; this reflects an effort by the chondrocytes to repair cartilage damage. This stage may last for years or decades and is characterized by hypertrophic repair of the articular cartilage.
As osteoarthritis progresses, however, the level of proteoglycans eventually drops very low, causing the cartilage to soften and lose elasticity and thereby further compromising joint surface integrity. Microscopically, flaking and fibrillations (vertical clefts) develop along the normally smooth articular cartilage on the surface of an osteoarthritic joint. Over time, the loss of cartilage results in loss of joint space.
In major weight-bearing joints of persons with osteoarthritis, a greater loss of joint space occurs at those areas experiencing the highest loads. This effect contrasts with that of inflammatory arthritides, in which uniform joint-space narrowing is the rule.
Erosion of the damaged cartilage in an osteoarthritic joint progresses until the underlying bone is exposed. Bone denuded of its protective cartilage continues to articulate with the opposing surface. Eventually, the increasing stresses exceed the biomechanical yield strength of the bone. The subchondral bone responds with vascular invasion and increased cellularity, becoming thickened and dense (a process known as eburnation) at areas of pressure
More Pathophysiology of Osteoarthritis
Erosion of the damaged cartilage in an osteoarthritic joint progresses until the underlying bone is exposed. Bone denuded of its protective cartilage continues to articulate with the opposing surface. Eventually, the increasing stresses exceed the biomechanical yield strength of the bone. The subchondral bone responds with vascular invasion and increased cellularity, becoming thickened and dense (a process known as eburnation) at areas of pressure
The traumatized subchondral bone may also undergo cystic degeneration, which is attributable either to osseous necrosis secondary to chronic impaction or to the intrusion of synovial fluid. Osteoarthritic cysts are also referred to as subchondral cysts, pseudocysts, or geodes (the preferred European term) and may range from 2 to 20 mm in diameter. Osteoarthritic cysts in the acetabulum are termed Egger cysts.
At areas along the articular margin, vascularization of subchondral marrow, osseous metaplasia of synovial connective tissue, and ossifying cartilaginous protrusions lead to irregular outgrowth of new bone (osteophytes). Fragmentation of these osteophytes or of the articular cartilage itself results in the presence of intra-articular loose bodies (joint mice).
Along with joint damage, osteoarthritis may also lead to pathophysiologic changes in associated ligaments and the neuromuscular apparatus. For example, lateral collateral ligament complex abnormalities are common in knee osteoarthritis.
Pain mechanisms in osteoarthritis
Pain, the main presenting symptom of osteoarthritis, is presumed to arise from a combination of mechanisms, including the following:
1. Osteophytic periosteal elevation
- Vascular congestion of subchondral bone, leading to increased intraosseous pressure
- Synovitis with activation of synovial membrane nociceptors
- Fatigue in muscles that cross the joint
- Overall joint contracture
- Joint effusion and stretching of the joint capsule
- Torn menisci
- Inflammation of periarticular bursae
- Periarticular muscle spasm
- Psychological factors
- Crepitus (a rough or crunchy sensation)
- Central pain sensitization
When the spine is involved in osteoarthritis, especially the lumbar spine, the associated changes are very commonly seen from L3 through L5. Symptoms include pain, stiffness, and occasional radicular pain from spinal stenosis. Foraminal narrowing is caused by facet arthritic changes that result in compression of the nerve roots. Acquired spondylolisthesis is a common complication of arthritis of the lumbar spine.
Etiology
The daily stresses applied to the joints, especially the weight-bearing joints (eg, ankle, knee, and hip), play an important role in the development of osteoarthritis. Most investigators believe that degenerative alterations in osteoarthritis primarily begin in the articular cartilage, as a result of either excessive loading of a healthy joint or relatively normal loading of a previously disturbed joint. External forces accelerate the catabolic effects of the chondrocytes and further disrupt the cartilaginous matrix.
Risk factors for osteoarthritis include the following: Age Obesity Trauma Genetics (significant family history) Reduced levels of sex hormones Muscle weakness Repetitive use (ie, jobs requiring heavy labor and bending) Infection Crystal deposition Acromegaly
Previous inflammatory arthritis (eg, burnt-out rheumatoid arthritis)
Heritable metabolic causes (eg, alkaptonuria, hemochromatosis, Wilson disease)
Hemoglobinopathies (eg, sickle cell disease and thalassemia)
Neuropathic disorders leading to a Charcot joint (eg, syringomyelia, tabes dorsalis, and diabetes)
Underlying morphologic risk factors (eg, congenital hip dislocation and slipped femoral capital epiphysis)
Disorders of bone (eg, Paget disease and avascular necrosis)
Previous surgical procedures (eg, meniscectomy)
Diabetes mellitus
Other Etiology
Advancing age
With advancing age come reductions in cartilage volume, proteoglycan content, cartilage vascularization, and cartilage perfusion. These changes may result in certain characteristic radiologic features, including a narrowed joint space and marginal osteophytes. However, biochemical and pathophysiologic findings support the notion that age alone is an insufficient cause of osteoarthritis.
Obesity
Obesity increases the mechanical stress in a weight-bearing joint. It has been strongly linked to osteoarthritis of the knees and, to a lesser extent, of the hips. A study that evaluated the associations between body mass index (BMI) over 14 years and knee pain at year 15 in 594 women found that a higher BMI at year 1 and a significant increase in BMI over 15 years were predictors of bilateral knee pain at year 15. [41] The association between BMI increase and knee pain was independent of radiographic changes.
In addition to its mechanical effects, obesity may be an inflammatory risk factor for osteoarthritis. Obesity is associated with increased levels (both systemic and intra-articular) of adipokines (cytokines derived from adipose tissue), which may promote chronic, low-grade inflammation in joints. [45]
Other causes
Trauma or surgery (including surgical repair of traumatic injury) involving the articular cartilage, ligaments, or menisci can lead to abnormal biomechanics in the joints and accelerate osteoarthritis. Although repairs of ligament and meniscal injuries usually restore joint function, osteoarthritis has been observed 5-15 years afterward in 50-60% of patients.
Insults to the joints may occur even in the absence of obvious trauma. Microtrauma may also cause damage, especially in individuals whose occupation or lifestyle involves frequent squatting, stair-climbing, or kneeling.
Muscle dysfunction compromises the body’s neuromuscular protective mechanisms, leading to increased joint motion and ultimately resulting in osteoarthritis. This effect underscores the need for continued muscle toning exercises as a means of preventing muscle dysfunction.
Genetics
A hereditary component, particularly in osteoarthritis presentations involving multiple joints, has long been recognized. [48, 49, 50] Several genes have been directly associated with osteoarthritis, and many more have been determined to be associated with contributing factors, such as excessive inflammation and obesity.
Osteoarthritis susceptibility genes (eg, ADAM12, CLIP, COL11A2, IL10, MMP3) have also been found to have differential methylation. Jefferies et al reports that hypomethylation of FURIN, which encodes a proprotein convertase, processes several ADAMTS molecules involved in osteoarthritic collagen degradation. Differential methylation among osteoarthritis susceptibility genes has been proposed as an alternative method for disruption of normal gene activity.
Additionally, Jefferies et al found evidence for hypermethylation and reduced expression of the type XI collagen gene COL11A2. Mutations involving COL11A2 have been associated with severe and early-onset osteoarthritis. Analysis by this goup has identified pathways enriched with “differentially methylated genes” that are effectors and upstream regulators seen in osteoarthritis linked with TGFB1 and ERG. [52]
Genes in the BMP (bone morphogenetic protein) and WNT (wingless-type) signaling cascades have been implicated in osteoarthritis. Two genes in particular, GDF5 (growth and differentiation factor 5) and FRZB (frizzled related protein), have been identified in the articular cartilage in animal studies and share a strong correlation with osteoarthritis.
