Sci. Aging Knowl. Environ., 1 September 2004
Vol. 2004, Issue 35, p. dn2
[DOI: 10.1126/sageke.2004.35.dn2]

NEURODEGENERATIVE DISEASE CASE STUDIES

Osteoarthritis

Najia Shakoor, and Richard F. Loeser

The authors are in the Section of Rheumatology at the Rush Medical College of Rush University Medical Center, Chicago, IL 60612, USA. E-mail: Najia_Shakoor{at}rush.edu (N.S.)

http://sageke.sciencemag.org/cgi/content/full/2004/35/dn2

Abstract: In this case study, we describe the symptoms, evaluation, and management of a woman with osteoarthritis (OA). OA is the most common form of arthritis worldwide and it is a major cause of disability in the elderly. Although there are several aging-related changes in the musculoskeletal system that may contribute to the pathogenesis of this disease, research suggests that OA is not merely an inevitable result of aging. OA is most likely a multifactorial process whereby non-aging-related factors also contribute to the onset, progression, and symptomatology of the disease. Specifically, both biochemical factors, including physiological properties of cartilage and bone, and biomechanical factors such as muscle strength, proprioception, and joint loading have been implicated in the pathogenesis of OA. Newer nonpharmacological treatment options are focusing on how to improve symptoms and prevent progression of the disease through mechanical interventions.

Introduction

A. A. is a 76-year-old female. She first saw her primary care physician with complaints of bilateral knee pain in 1999. Her pain has slowly increased over the past 5 years and is now constant, primarily localized to the inner part of the knees, and is more severe in her right knee. She uses a cane to help her walk. A. A. notices occasional swelling of her knees and says that her knees have become "larger" over the past few years. She complains of general stiffness, particularly in the morning, that lasts for 15 to 20 minutes. She has also observed enlargement of the joints in her hands and frequently experiences stiffness and pain there. A. A. has been taking 4000 mg daily (maximum dose) of acetaminophen without much relief of her pain.

Medical History

A. A. is overweight. She suffers from high blood pressure and chronic renal insufficiency. She has also suffered from ulcer disease in her stomach. She is taking amlodipine for her blood pressure and acetaminophen for her arthritis pain. Her doctor has suggested that she avoid nonsteroidal anti-inflammatory medications in light of her kidney and stomach problems. She is not aware of any allergies to medications.

Social History

A. A. lives alone in a three-story building. She lives on the second floor and has difficulty climbing the stairs to reach her apartment. She also has difficulty climbing into the bathtub. Her daughter lives a few miles away and helps with grocery shopping. A. A. does not smoke or drink alcohol.

Family History

A. A.'s mother was also overweight and suffered from arthritis in her knees. Her younger sister suffers from elevated blood pressure.

Musculoskeletal Examination

A. A. is 5 feet 4 inches tall and weighs 186 pounds. Some of her finger joints are enlarged. This enlargement is different from the enlargement typically associated with the inflamed swollen joints of rheumatoid arthritis patients because her joints are hard and bony to the touch. Both her hips have a fairly normal range of motion. Bony enlargement of her knees is also evident. There is no evidence of effusions, but both knees exhibit crepitus, a grinding or crackling noise or sensation felt over the joint. The medial joint line of both knees is tender upon palpation. A. A. has limited range of motion in her knees; they can only be flexed to 90 degrees, whereas most normal people's knees can be flexed to 120 degrees. She cannot completely straighten her knees either. A. A.'s muscle strength and deep tendon reflexes appear to be normal and symmetric. When she stands, she appears to be "bowlegged" (Fig. 1). When she walks, she has a notable limp, with a tendency to lean to the left side of her body.



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Fig. 1. A. A. demonstrates varus alignment, or a "bow-legged" appearance of her lower extremity. This malalignment may be a consequence of her arthritis but may also be a risk factor for further progression of her arthritis.

 
Radiological Testing

X-ray films of A. A.'s knees reveal significant narrowing of the medial joint space of both knees with sclerosis and osteophytes (Fig. 2). Sclerosis refers to thickening of the bone. This can usually be seen on x-ray as a thicker "white" margin at the end of the bone. Osteophytes are bony outgrowths at the margins of the joint space. The knee has a medial and lateral joint space formed from articulation of the femur with the tibia. The medial joint space (the inner part of the knee) is most commonly affected in knee OA.



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Fig. 2. Standing radiographs of the knees demonstrate severe narrowing and sclerosis of the medial joint space with bony growth, or osteophytes, at the joint margins.

 
Laboratory Testing

Sedimentation rate and C-reactive protein, indicators of systemic inflammation, were not elevated. These inflammatory indicators are often elevated in patients with primarily inflammatory arthropathies such as rheumatoid arthritis. However, they are usually normal in OA. The serum creatinine concentration was elevated at 1.7 mg/dl (normal is 0.6 to 1.3 mg/dl), which suggests decreased kidney function.

Clinical Diagnosis

A. A. was diagnosed with OA affecting the knees and hands. OA has an insidious, but often progressive, course and patients may have symptoms for several years before the disease is recognized or brought to the attention of a physician. The large lower-extremity joints (hips and/or knees) are most commonly affected, but the hands are often affected as well. For reasons that remain unclear, certain joints, including the wrist, shoulder, and ankle, are often unaffected. Characteristic features of OA include slowly progressive symptoms of pain over a period of years. The arthritis is traditionally described as having an asymmetric distribution of joint involvement in contrast to the bilateral, symmetrical pattern of joint involvement seen in rheumatoid arthritis. OA patients also complain of morning stiffness lasting less than 15 minutes, in contrast to inflammatory arthritic conditions in which morning stiffness can last an hour or longer. Common findings upon physical examination include bony enlargement of the affected joints, limited range of motion of the joints, and crepitus. A. A. demonstrated all of these features, including bony enlargement of the hand joints, referred to as Heberden's nodes and Bouchard's nodes (Fig. 3).



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Fig. 3. The distal and proximal interphalangeal joints of the hands show bony enlargements referred to as Heberden's and Bouchard's nodes, respectively.

 
Pathologically, OA is characterized by cartilage loss and bony growth. These features can typically be seen in radiographs in which asymmetrical narrowing of the joint space indicates loss of cartilage and the presence of osteophytes at the margins of joints indicates bony growth. Generalized joint enlargement is also indicative of bony growth. Seventy percent of OA cases primarily involve the medial compartment of the knee, and at the end stages of the disease this joint space may be completely obliterated.

Risk Factor Evaluation and Pathogenesis

Age is one of the major risk factors for OA. By the age of 60, more than 80% of individuals will have radiographic evidence of OA in at least one joint, and nearly 40% will have self-reported arthritis. The discrepancy between radiographic findings and symptoms is well recognized. Patients can have radiographic evidence of OA and not have symptoms of pain. Similarly, elderly patients, perhaps because of age-related decline in physical activity, can have functional limitations and pain without radiographic signs of OA. Thus, both age-related changes and OA-related changes, with some overlap between the two, can contribute to pain and disability in the elderly.

Women may also be at greater risk for developing OA than men. Studies suggest that after the age of 50, the incidence of knee OA is greater in women compared with men. This pattern has been attributed to the hormonal changes associated with menopause, as well as to differences in physical activity and anatomy between men and women. Therefore, A. A. has both age and gender as risk factors for the disease.

Abnormal joint loading is a central feature in the biomechanical paradigm for the pathogenesis of OA. Conceptually, if a normal joint is subjected to "abnormal" loads, it could develop the clinical features of OA, including pain, cartilage loss, and joint space narrowing. The abnormal loads can be static loads or dynamic loads experienced by the joint during movement. Obesity, a strong risk factor also displayed by A. A., is considered a static load. Some studies suggest that there is a 40% increase in risk of knee OA with every 10-pound increase in body weight. Dynamic loads are thought to be particularly important in the pathogenesis of joint deterioration because the amount of load placed on the knee while walking is three times as great as the load placed on the knee while standing. Internal joint transducers are devices that can be surgically implanted into the joint to measure loads at the joint during walking. Gait analysis is an alternative, reliable, and practical technique to indirectly assess loads that occur dynamically. During gait analysis, patients walk at a range of self-selected speeds from slow to fast on a multicomponent force plate. Reflective markers are placed on the bony landmarks of the lower extremity. The markers provide reference points for locating the internal joint centers and allow for assessment of hip, knee, and ankle motion by using a three-dimensional coordinate system. Intersegmental forces and external moments can thus be calculated. Gait symmetry can be evaluated and the loading parameters most strongly associated with OA can be studied. For example, the external knee adduction moment is a dynamic measure of loading at the medial compartment of the knee. This higher external knee adduction moment has been associated with both prevalence and increased severity of OA, and it has been found to predict increased progression of knee OA.

In addition to dynamic joint loads, neuromuscular deficiencies have been implicated in the pathogenesis of OA. Muscles are thought to act as the body's shock absorbers. Studies show not only that muscle strength declines with age but also that such decline may be a primary risk factor for knee OA. Obviously, muscle weakness could be a result of pain and decreased physical activity in patients with OA. However, quadriceps muscle weakness has been recognized in asymptomatic individuals with only radiographic evidence of knee OA. Muscle weakness in OA patients may not be apparent from a normal musculoskeletal physical exam but can be measured with special instruments such as isokinetic dynamometers and compared with the muscle strength of normal patients of similar age.

In addition, patients with knee OA show decreased sensory processing, and decreased proprioceptive acuity in particular. Proprioception is the ability to reproduce an angular position in space or the ability to detect movement of the limb in space. Similar to the shock-absorbing role of muscles, appropriate proprioceptive acuity is felt to prevent impulsive jarring forces on the joint. Proprioceptive acuity also decreases with age.

Lower-extremity alignment may also have mechanical roles in the pathogenesis of OA. A. A.'s legs appear "bow-legged." This is referred to as varus alignment of her legs, in contrast with valgus alignment in which the legs have a "knock-kneed" appearance. The varus deformity may be a result of narrowing of the medial compartment of the knee. However, malalignment is also considered a risk factor for medial knee OA and may predispose to further narrowing of the joint space.

Other risk factors for OA include genetic factors, anatomical factors, and injury. A. A. had a mother who suffered from OA; as there does seem to be a genetic predisposition to arthropathy, her mother's condition is a risk factor for A. A. Pelvic anatomy might predispose someone to the development of early hip OA, and previous joint injury, such as a tear of the meniscus at the knee, has been shown to predispose to the development of OA as well.

At the tissue level, OA is characterized by a progressive degradation and loss of articular cartilage, which is accompanied by hypertrophy of neighboring bone. The cartilage normally functions to provide a smooth surface to allow for normal joint motion, and therefore the cartilage destruction in OA compromises joint function. It appears that in OA, cartilage cells called chondrocytes produce excess amounts of degradative enzymes, including several metalloproteinases, which act to break down the cartilage matrix. Aging might contribute to the development of OA by making the cartilage more susceptible to breakdown and/or less capable of repairing matrix damage (see Loeser Perspective).

The pathogenesis of OA appears to be multifactorial. Like A. A., most patients with OA have several risk factors for arthropathy. Although many of the changes in the musculoskeletal system that occur with age might predispose older people to the development of OA, age-independent factors are also involved in the pathophysiology of the disease.

Treatment

Because most patients afflicted with OA are elderly, many have other chronic illnesses or limitations in physical function. Such pre-existing conditions can interfere with the treatment of these individuals and contribute substantially to their disability. Therefore, improvements in disability and functional capacity are major therapeutic goals for these patients, in addition to pain relief.

Unfortunately, treatment options for OA are limited. Elderly patients with OA often have contraindications to or do not respond to available pharmacological interventions. In these cases, nonpharmacological treatment strategies are recommended. Several of these treatments are directed at improving lower-extremity biomechanics. Physical therapy, for example, is a long-standing and well recognized therapeutic intervention for OA. Aerobic or resistance-training exercise programs can significantly reduce pain and improve muscle strength and function. However, the long-term benefit of these exercises on the progression of OA is not yet clear.

Newer, noninvasive biomechanical interventions include knee braces and orthotics. Sleeve-type knee braces were initially used in patients with anterior cruciate ligament injuries but have been shown to improve proprioceptive acuity in knee OA. Similarly, valgus-type knee braces are also available and have been shown to improve symptoms of pain, as well as to reduce the medial compartment load in patients with knee OA. Orthotics or laterally elevated wedge insoles can alter the spatial positioning of the lower limb so as to decrease the varus torque or medial compartment load on the knee. These insoles can be custom made and have been shown to decrease the peak external knee adduction moment during walking. Long-term studies to evaluate the utility of orthotics in preventing the progression of knee OA are under way.

Acetaminophen, nonsteroidal anti-inflammatory agents, and other analgesic medications are the mainstays of pharmacological intervention for OA. Nonsteroidal agents, including new COX-2 inhibitors that have a lower risk of causing gastrointestinal ulcers and bleeding, are often contraindicated for use in elderly patients. A. A. has a history of peptic ulcer disease as well as renal insufficiency, both of which precluded the use of these drugs for her arthritis. Because acetaminophen alone is not controlling her pain, she may need alternative analgesics such as tramadol or narcotic-type analgesics to relieve her symptoms. She could also try localized pharmacological treatments such as topical analgesics and knee injections with corticosteroids or hyaluronic acid derivatives. Intraarticular steroids can provide pain relief for most patients for a few weeks, whereas intraarticular hyaluronic acid may provide longer term pain relief (for a few months) but does not appear to be effective in all patients.

For patients with end-stage knee OA, both nonpharmacological and pharmacological treatments may be ineffective. For patients who experience substantial pain and disability despite conservative therapy, total joint replacement surgery may be an effective treatment option. In fact, OA is the most common indication for the total joint replacement of the hip and knee worldwide. The appropriate time for joint surgery varies according to the age, lifestyle demands, pain tolerance, and preferences of individual patients. Nevertheless, recent studies have suggested that earlier surgery--before the development of substantial disability, deformity, and muscle strength deficits--may lead to better postoperative outcomes.

Discussion

OA is a chronic, insidious, and debilitating disease. As in the case with A. A., patients may have mild symptoms for many years that slowly progress in severity and eventually lead to major disability.

A. A. received a corticosteroid injection into her right knee, followed by 8 weeks of physical therapy. Her symptoms improved substantially after these interventions, and her muscle strength and functional ability improved as well. A. A. will undoubtedly experience intermittent exacerbations of her disease, and the arthropathy may continue to progress. She has been advised to continue home physical therapy exercises indefinitely and to make them part of her daily routine. She may eventually require a total knee replacement. Continued physical therapy will not only help her present symptoms but will place her in a better physical position to undergo and recover from surgery.


September 1, 2004

Abbreviations: Abnormal joint loading: Excessive or detrimental forces placed on joints. • Amlodipine: A medication from the class of calcium channel blockers; often used to treat elevated blood pressure. • Arthropathy: A disease affecting a joint. • Articular cartilage: Nonvascular compressible connective tissue that covers the surface of bones in joints. • Bouchard's nodes: Bony growths about the size of a pea or smaller found on the proximal phalanges of the fingers in osteoarthritis. • Chondrocytes: Cartilage cells. They are responsible for maintenance of the tissue. • Chronic renal insufficiency: Decreased function of the kidneys, which develops and progresses slowly over time. • COX-2: One form of the enzyme cycloxygenase, which catalyzes the metabolism of arachidonic acid. COX-2 is the form primarily involved in the production of inflammation-induced prostaglandins. • C-reactive protein: A protein produced by the liver, usually in response to a systemic illness or infection. This protein is used as an indicator of the presence and severity of inflammation. • Creatinine: A normal metabolic waste product of creatine metabolism; generally produced and secreted by the kidney at a constant rate. The serum level of creatinine can therefore be used as a measure of kidney function. • Crepitus: A grating sensation or noise that a joint makes with movement, often attributed to damaged cartilage. • Deep tendon reflexes: Involuntary and immediate contractions of a muscle upon tapping of its associated tendon. • Effusions: Fluid surrounding the joint; usually a sign of joint inflammation. • External knee adduction moment: A measure of torque/force measured through gait analysis. This measurement represents loading at the medial compartment of the knee. • Gait analysis: A noninvasive technique used to evaluate ambulation, in particular the distribution of load placed on joints during ambulation. • Heberden's nodes: Bony growths about the size of a pea or smaller found on the terminal phalanges of the fingers in osteoarthritis. • Hyaluronic acid: A viscous material present in synovial fluid and certain tissue spaces; also available pharmacologically as an injectable medicine for the treatment of knee OA. • Hypertrophy: General increase in bulk. • Internal joint transducers: Devices that are surgically implanted into joints to measure internal pressures and forces at the joint. • Intraarticular steroids: A family of chemical substances with anti-inflammatory properties, which can be injected into joints. • Isokinetic dynamometers: Specialized instruments primarily used to measure muscle strength. • Medial joint line: The knee joint consists of articulation of the femur with the tibia. The medial joint space or line refers to the area between the medial aspect of the femur and the medial tibial plateau; the lateral joint space would be the adjacent space formed by the meeting of the lateral aspect of the femur and the lateral tibial plateau. • Metalloproteinases: A family of enzymes that degrade matrix proteins and require specific metal ions for activity. • Proprioceptive acuity: The ability to detect movement or position of a limb in space. • Rheumatoid arthritis: A systemic, inflammatory, immune-mediated arthritis usually affecting young to middle-aged women. • Sedimentation rate: The rate at which red blood cells settle out in a tube of blood under standardized conditions. A high sedimentation rate usually indicates the presence of inflammation. • Tramadol: An opioid agonist-antagonist used as an analgesic to treat pain. • Valgus alignment: Bent away from the midline. • Varus alignment: Bent toward the midline.

Suggested ReadingBack to Top

  • Recommendations for the medical management of osteoarthritis of the hip and knee: 2000 update. American College of Rheumatology Subcommittee on Osteoarthritis Guidelines. Arthritis Rheum. 43, 1905-1915 (2000).
  • D. T. Felson, R. C. Lawrence, P. A. Dieppe, R. Hirsch, C. G. Helmick, J. M. Jordan, R. S. Kington, N. E. Lane, M. C. Nevitt, Y. Zhang et al. Osteoarthritis: New insights. Part 1: The disease and its risk factors. Ann. Intern. Med. 133, 635-646 (2000). [Abstract]
  • D. T. Felson, R. C. Lawrence, M. C. Hochberg, T. McAlindon, P. A. Dieppe, M. A. Minor, S. N. Blair, B. M. Berman, J. F. Fries, M. Weinberger et al. Osteoarthritis: New insights. Part 2: Treatment approaches. Ann. Intern. Med. 133, 726-737 (2000). [Abstract]
  • R. F. Loeser, N. Shakoor. Aging or osteoarthritis: Which is the problem? Rheum. Dis. Clin. North Am. 29, 653-673 (2003). [Abstract]
  • Dr. Shakoor's work was supported by an American College of Rheumatology/Research and Education Foundation/Association of Subspecialty Professors Junior Career Development Award in Geriatric Medicine and by the National Institute of Arthritis and Musculoskeletal and Skin Diseases (AR049748). Dr. Loeser was supported by the National Institute on Aging (AG16697).
Citation: N. Shakoor, R. F. Loeser, Osteoarthritis. Sci. Aging Knowl. Environ. 2004 (35), dn2 (2004).








Science of Aging Knowledge Environment. ISSN 1539-6150