Essentials of Diagnosis Joint pain brought on and exacerbated by activity and relieved with rest.

Stiffness that is self-limited upon awakening in the morning or when rising from a seated position after an extended period of inactivity. Absence of prominent constitutional symptoms. Examination notable for increased bony prominence at the joint margins, crepitance or a grating sensation upon joint manipulation, and little if any associated joint effusion. Diagnosis supported by radiographic features of joint space narrowing and spur (or osteophyte) formation. General Considerations Osteoarthritis is the leading cause of arthritis in the adult American population and affects an estimated 20 million people in the United States. Joint pain is a frequent symptom that often prompts a patient to seek medical attention, for which osteoarthritis figures prominently in the differential diagnosis. The challenge for clinicians is to correctly identify the cause of the patient's pain and to initiate appropriate therapy, both medicinal and nonmedicinal. Synonymous with degenerative joint disease, osteoarthritis is characterized by joint pain related to use, the absence of pain at rest, self-limited morning stiffness, an audible grating sound or crepitus on palpation, reduction in joint range of motion, and minimal to no associated joint swelling or warmth. Characteristic sites of involvement in the peripheral skeleton include the hand (distal interphalangeal joint, proximal interphalangeal [PIP] joint, and first carpometacarpal joint), knee, and hip. Common axial sites with a predilection for osteoarthritis are the lumbar and cervical spine. Constitutional symptoms are characteristically absent. Other than pain or discomfort in the involved joint, the patient with osteoarthritis most often feels well and reports good health. The diagnosis of osteoarthritis can usually be made relatively easily and confidently based on the history and examination alone. The bedside diagnosis of osteoarthritis can be supported by plain radiography. Epidemiology At the population level, osteoarthritis results in substantial morbidity and disability, particularly among the elderly. It is the leading indication for several hundred thousand knee and hip replacement surgeries performed each year in the United States. Therefore, much effort has been invested in improving the understanding of the epidemiology of this disorder, including identifying the factors that predispose persons to osteoarthritis, especially those risk factors that

are reversible or modifiable. Several factors heighten the risk of incident osteoarthritis, including age, gender, and joint injury. While the clinical expression of osteoarthritis begins to manifest during the fourth and fifth decades of life, the incidence of osteoarthritis continues to increase with each decade of aging. Moreover, women in their 50s, 60s, and 70s have a greater prevalence of osteoarthritis in the hand, knee, and hip than do men. There is evidence to suggest that racial differences exist in osteoarthritis prevalence, with greater frequency of knee osteoarthritis in African Americans than in white Americans. Also, prior trauma to a previously pristine joint, such as a ruptured anterior cruciate ligament or torn medial meniscus, increases the risk of later osteoarthritis at that joint site.

Pathogenesis The pathophysiology of this disorder is related to excessive degradation of cartilage within the involved joint. Elevated production of degradative metalloproteinases, including collagenases, results in tissue breakdown and disruption in assembly of the extracellular matrix. This disruption to the structural integrity of articular cartilage in turn leads to functional compromise of the patient

Prevention At present, there are no definitive data available from randomized controlled trials regarding what preventive measures can be taken to reduce a patient's risk of developing osteoarthritis. While certain factors, such as age, gender and race, cannot be altered, others such as body weight are more amenable to modification. Moreover, findings from observational studies suggest that weight loss and a change in dietary patterns may reduce a patient's risk of developing osteoarthritis at the knee or diminish the probability of osteoarthritis progression. Among women who participated in the Framingham Osteoarthritis Study, those who experienced a 5-kg or more weight reduction over 10 years had half the risk of developing symptomatic knee osteoarthritis. Such data support the claim that weight reduction can alter the risk of developing osteoarthritis. Moreover, higher levels of vitamin D in serum and in the diet and greater intake of vitamin C were associated with a reduced risk of disease progression. Dietary consumption of these nutrients was not, however, related to the risk of developing new, or incident, osteoarthritis.

Clinical Findings Symptoms and Signs The patient with osteoarthritis affecting a joint in the peripheral skeleton, such as the finger, knee, or hip, may initially experience relatively minor pain or discomfort with use of the

involved joint (Table 421). For example, at the outset of osteoarthritis involving the hip joint, patients may have some difficulty crossing their legs to put on a pair of shoes or pants; however, once they are dressed and upright, bearing weight and ambulation are still well tolerated. As osteoarthritis progresses, a patient will gradually experience progressively severe joint discomfort and increasing difficulty with related activities of daily living.

Table 421. Signs, Symptoms, and Diagnostic Features of Osteoarthritis. With further disease progression, such as at an osteoarthritic hand or finger, increasing difficulty with previously routine activities often follows. Thus, even gripping, holding, or writing with a pen or pencil can be a painful feat to accomplish. Putting car keys in and turning the ignition switch, lifting a gallon of milk out of the refrigerator, or removing a pot of water from the stove can become quite difficult tasks to accomplish. At this stage, the signs of osteoarthritis joint involvement include bony enlargement of the involved joint and possibly joint misalignment. At the extreme end of the disease spectrum, marked impairment in activity follows. Even walking from room to room in one's home may be unbearably painful when advanced or end-stage osteoarthritis affects the hip or knee joint. Laboratory Findings There is no specific laboratory test that is used in clinical practice to confirm a diagnosis of osteoarthritis. Instead, routine laboratory blood testing, including complete blood cell counts, acute phase reactants (erythrocyte sedimentation rate and C-reactive protein), and screening autoantibodies (rheumatoid factor and antinuclear antibody) are of value in their negativity. These parameters may be of key diagnostic value when determining whether particular signs and symptoms in the hand represent underlying osteoarthritis or rheumatoid arthritis. Thus, normal white blood cell and platelet counts, the absence of anemia, normalcy of acute phase reactants, and seronegativity for rheumatoid factor are each expected in the patient whose PIP joint changes are the result of bony remodeling and joint space narrowing from osteoarthritis (termed "Bouchard nodes") rather than the result of active rheumatoid synovitis, which may affect this same joint group.

Imaging Studies Radiographic imaging can confirm the diagnosis of osteoarthritis. More than 4 decades ago, Kellgren and Lawrence described characteristic radiographic features of osteoarthritisjoint space narrowing, osteophytes, subchondral cysts, and bony sclerosis (eburnation). To the present, these parameters remain the radiographic hallmarks of osteoarthritis. While scintigraphy (bone scan) may reveal increased radionuclide uptake at osteoarthritic joints and computed tomography and magnetic resonance imaging may demonstrate characteristic radiographic features of osteoarthritis, these imaging modalities are not routinely used to confirm the diagnosis of osteoarthritis. Special Tests Pursuit of a histologic diagnosis via synovial or bone biopsy is not a conventional strategy in the evaluation of a patient with suspected osteoarthritis. However, in the appropriate setting, a joint tap is a valuable test when encountering a patient with presumptive osteoarthritis. When there is subtleif not moderate evidenceof a mild joint effusion, diagnostic arthrocentesis may be a key aid to confirm the clinical impression. This is because a synovial fluid cell count of 200 2000 cells/ L is characteristic of an osteoarthritic effusion; this synovial fluid white blood cell count is intermediate between the upper bound of normal and the lower bound of an inflammatory arthritis.

Differential Diagnosis The challenge when evaluating a patient with joint pain is to effectively use the history, examination, and available tests to arrive at the correct diagnosis. The presence of pain at the symptomatic joint, brought on by activity and relieved with rest, is quite suggestive of a degenerative arthropathy. Moreover, the absence of constitutional signs and symptoms and the presence of bony enlargement at the joint margin, with little if any evidence of joint inflammation, serve to reinforce this clinical impression. Finally, the pattern of joint involvement is meaningful because primary osteoarthritis has a predilection for particular joint sites in the peripheral skeleton, predominantly the hands (distal interphalangeal joints, PIP joints, first carpometacarpal joint), knees, and hips. The cervical and lumbar spine are preferentially involved sites of involvement in the axial skeleton. These features serve to distinguish osteoarthritis from inflammatory arthropathies (such as rheumatoid arthritis and gout) that have overlapping sites of involvement. It is also worth noting that a variety of secondary disorders represent identifiable causes of osteoarthritis. Several such disorders, including those resulting from inborn errors of metabolism and metabolic derangements, are listed in Table 422. Recognition of their distinct features, such as predilection for involvement of the second and third metacarpophalangeal joints in hemochromatosis-associated arthropathy, may serve to identify the true underlying cause of the joint pain and may impact upon therapeutic decision making. Finally, one need also bear in mind that the presence of known osteoarthritis does not negate consideration of an alternate

explanation, such as an occult malignancy, when a meaningful change in the pattern of joint pain occurs.

Treatment Notwithstanding the substantial population burden and the deleterious impact on quality of life for affected persons, there is no known curative therapy for osteoarthritis. Nevertheless, conventional treatment has been demonstrated to reduce symptoms and improve function and quality of life in randomized clinical trials. Goals of therapy are to control pain, improve function, minimize disability, and enhance health-related quality of life. It is a priority to furnish the patient and his or her family with appropriate education and understanding on this disorder as well as reasonable expectations regarding the course and hazards of therapy. A further therapeutic priority is to minimize, if not avoid altogether, drug-associated toxicity, particularly that which may result from nonsteroidal anti-inflammatory drug (NSAID) therapy. A specific set of guidelines regarding the medical management of osteoarthritis at the knee and hip joints has been published by the American College of Rheumatology. The major goals of therapy are the alleviation of pain and improvement in function. In patients with mild to moderate osteoarthritis, therapeutic benefit can often be achieved without resorting immediately to the use of prescription medication. For example, an assistive device, such as a cane or walker, can be substantially beneficial. Similarly, quadriceps strengthening and aerobic exercise have been shown to be effective in the management of osteoarthritis at the knee. In terms of nonprescription therapy, it is also pertinent to inquire about what other forms of therapy the patient may be taking. For example, many persons resort to alternative medicine modalities, including ingestion of shark tooth cartilage, application of magnets to osteoarthritic joints, or standing in front of an electromagnetic field. A front-line approach to medicinal therapy for osteoarthritis includes use of acetaminophen. This drug has been demonstrated to be effective in improving pain and function and has a safer

toxicity profile, particularly with regard to the gastrointestinal tract, than other NSAIDs. For many years, the NSAIDs have been widely used in the management of osteoarthritis. Via their inhibition of cyclooxygenase (COX), particularly the inducible isoform at sites of joint damage, symptomatic benefit is achieved. However, the toxicity profile of NSAID therapy remains a major concern, at both the individual and population aggregate level. An estimated 10,000 Americans die each year of gastrointestinal complications resulting from NSAID therapy. The following factors increase the risk of such toxicity: Persons with prior peptic ulcer disease. Persons older than 65 years. Concomitant tobacco and alcohol use. Coadministration of glucocorticoids or anticoagulation therapy. Comorbid Helicobacter pylori infection. In 1999, a new category of NSAID agents, the selective COX-2 antagonists, that selectively and preferentially inhibit the inducible isoform at the site of joint injury (but not the constitutive form of the enzyme that has gastroprotective properties) was introduced into the marketplace. Their use has exploded in just the last 4 years, on the strength of furnishing a safer gastrointestinal profile. However, this improved safety profile has been questioned, including concern of an enhanced cardiovascular toxicity profile that may offset the improved gastrointestinal benefits. Increasing evidence now exists to support use of glucosamine sulfate, a component of human articular cartilage, in the medical management of osteoarthritis. In particular, two recent European reports have furnished evidence from randomized, placebo-controlled trials that demonstrated improvement in joint pain and functionality in patients with knee osteoarthritis managed with oral glucosamine at a dose of 1500 mg/d compared with placebo. Moreover, in both trials glucosamine was also shown to halt radiographic progression of joint space narrowing. The concept that a therapeutic intervention may actually arrest or reverse structural compromise to an osteoarthritic joint is a novel and highly noteworthy development in the management of osteoarthritis. Whether similar benefit may be accrued with use of chondroitin sulfate (also commercially available)or whether additive benefit can be obtained from concomitant administration of both glucosamine and chondroitinremains to be determined. Complications After a diagnosis of osteoarthritis has been firmly established, subsequent change in symptoms or course will not necessarily be directly attributable to the known osteoarthritis. Such a change ought to command the clinician's attention to search for, or at least entertain, the possibility of an alternate consideration (Table 423). For example, the abrupt onset of heat, redness, and swelling in a known yet previously stable osteoarthritic knee may herald the onset of a

superimposed microcrystalline arthritis or of a ruptured Baker (or popliteal) cyst. Alternately, new-onset joint locking or giving way may suggest the presence of a loose body that warrants arthroscopic intervention before a catastrophic fall were to occur. Similarly, nerve entrapment from a spinal osteophyte encroaching upon an exiting nerve root in the foraminal space may lead to new or rapidly progressive burning or electrical pain in the affected extremity. Not to be forgotten is that a change in symptoms in the region of an osteoarthritic join may also be attributable to active inflammation of adjacent nonarticular tissues, including regional tendons and bursae

When to Refer to a Specialist An important consideration when weighing the merit of referral to a specialist is whether there exists a lack of diagnostic clarity. This is particularly germane when the clinician's judgement suggests that a given patient's symptoms are poorly explained by invoking osteoarthritis as the underlying cause. This concern often arises because of the high background prevalence of osteoarthritis in the general population. For example, even though clinical and radiographic evidence of osteoarthritis may be present, ongoing symptoms may be attributable to an unrelated superimposed process. A second opinion is also advisable when a patient's pain and functional decline appear refractory to treatment. Finally, evaluation by an orthopedic surgeon is in order when the persistence of symptoms and functional decline necessitate consideration of joint replacement surgery. Future Directions Ongoing research in this field is largely directed at identification of factors that predispose some but not all aging adults to the development of osteoarthritis. In addition, there is an intense effort underway to identify biomarkersof bone and cartilage turnoverthat may identify those at risk for osteoarthritis and those at risk for disease progression. In the future, availability of drug therapy that may inhibit the adverse effects of degradative enzymes or promote the growth of deficient cartilaginous structures will be critical to realizing therapies that may effectively control, if not cure, osteoarthritis.