Osteoarthritis
Authors:
Terrence C. Tan, DO, Rheumatology Fellow, Loma Linda University, Loma Linda, CA.
Zahra Shahim, MD, Medicine Resident, Loma Linda University, Loma Linda, CA.
Keith K. Colburn, MD, FACP, FACR, Professor of Medicine, Chief of Rheumatology, Loma Linda University and Loma Linda VA Medical Center, Loma Linda, CA.
Peer Reviewer:
Robert A. Hawkins, MD, FACR, Associate Professor of Medicine, Wright State University, Dayton, OH; Associate Residency Program Director, Internal Medicine Residency Program, Kettering Medical Center, Kettering, OH.
Statement of Financial Disclosure
To reveal any potential bias in this publication, and in accordance with Accreditation Council for Continuing Medical Education guidelines, we disclose that Dr. Farel (CME question reviewer) owns stock in Johnson & Johnson. Dr. Stapczynski (editor) owns stock in Pfizer, Johnson & Johnson, AxoGen, Walgreens Boots Alliance Inc., and Bristol Myers Squibb. Ms. Mark’s spouse (executive editor) works for a company that creates advertising for Uroplasty. Dr. Schneider (editor), Dr. Colburn (author), Dr. Tan (author), Dr. Shahim (author), Dr. Hawkins (peer reviewer), Dr. Wise (editor), and Mr. Landenberger (editorial director) report no financial relationships with companies related to the field of study covered by this CME activity.
Osteoarthritis
Osteoarthritis does not seem initially like a topic that has much relevance to emergency medicine. After all, what is acute or emergency about it? In reality, as we all know, patients come to the ED with undifferentiated symptoms, including joint pain. Many times, this joint pain is due to undiagnosed osteoarthritis. When I tell patients this is what they have, they have many questions in return. After reading this article, I feel better able to answer these questions. I also feel more confident in my initiation and adjustment of the NSAIDs used in treating these patients.
—J. Stephan Stapczynski, MD, FACEP, Editor
Introduction
Osteoarthritis (OA) can be described as the failed repair of damage that has been caused by excessive mechanical stress (defined as force/unit area) on joint tissues.1 This implies that although multiple factors may lead to OA, mechanical impact (either as a major single event or as repetitive micro trauma) is central to all of these. Also known as osteoarthrosis or degenerative joint disease, OA is the most important chronic musculoskeletal disorder in humans.
Although not a life-threatening disease, OA is considered one of the major concerns in human health care because of the vast number of people involved and the severe impact this literally crippling disease can have on quality of life.
Contribution of Osteoarthritis to Functional Limitations and Disability
Arthritis is the leading cause of disability among adults,2-10 and there is no question that OA in particular is related to disability as adults age. The risk of OA increases with age, so that by the age of 80 years, radiographic evidence of joint degeneration is found in nearly everyone.11
OA pathology results in the degeneration of cartilage, bone, and soft tissues integral to joints, most commonly the hand, knee, hip, spine, and foot. Although OA is associated with joint-related symptoms such as pain and stiffness, there is wide variation in symptoms for those with radiographic evidence of joint degeneration changes, and many with radiographic changes report no pain.12
Pathogenesis
One of the main mechanisms for the development of OA is damage to the articular cartilage by trauma, which in turn causes chondrocytes to release degradative enzymes leading to abnormal repair of the matrix.13-16 This in turn causes the subsequent development of OA. Cartilage from osteoarthritic joints is thought to deform more easily compared to normal joint tissue in response to the same mechanical load.17
Chondrocytes maintain homeostasis of the articular cartilage by synthesizing collagens, proteoglycans, and proteinases. OA develops when there is failure of these chondrocytes to maintain this homeostasis between synthesis and degradation.
Osteoblasts also play a role in the formation of OA. These osteoblasts in OA patients produce more alkaline phosphatase, osteocalcin, insulin-like growth factor, and urokinase in comparison to normal osteoblasts leading to degradation of the cartilage matrix.
Certain cytokines such as IL-1, tumor necrosis factor alpha, insulin-like growth factor, transforming growth factor-beta, and interleukin-6 were shown to play a role in OA. There is an increased level of IL-1 in the joints of patients with knee OA compared to those without OA. Tumor necrosis factor alpha is increased in the joints of OA patients.18 Insulin-like growth factor increases cartilage and matrix synthesis and is decreased in the joints of OA patients. Another cytokine known to maintain cartilage, called transforming growth factor-beta, is found in low levels in osteoarthritic joints.19 Interleukin-6 has a complex role in OA. This cytokine, which is a modulator in cartilage remodeling and degradation, was shown to be increased in osteoarthritic joints, to increase TNF receptors (which causes breakdown of cartilage), and to increase the production of tissue metalloproteinase-1 (which inhibits breakdown of cartilage).
Nitric oxide also plays a role in the pathogenesis of OA. In OA patients, nitric oxide is produced in the joints in large amounts. Nitric oxide is partly responsible for blocking glycosaminoglycan and collagen synthesis by IL-1 and activating metalloproteinases.
The risk of OA progression increased three-fold in patients with low vitamin D intake.20 However, low intake and serum levels of vitamin D did not increase the risk for developing OA.
Etiology, Incidence, and Risk Factors
OA is a normal result of aging.21 It is also caused by “wear and tear” on a joint. Cartilage is the firm, rubbery tissue that cushions the bones at the joints, and allows bones to glide over one another. If the cartilage breaks down and wears away, the bones rub together. This causes pain, swelling, and stiffness. Bony spurs or extra bone may form around the joint. The ligaments and muscles around the joint become weaker and stiffer.
OA symptoms usually appear in middle age. Almost everyone has some symptoms by age 70. However, these symptoms may be minor. Before age 55, OA occurs equally in men and women. After age 55, it is more common in women.21
OA tends to run in families. Being overweight increases the risk of OA in the hip, knee, ankle, and foot joints because extra weight causes more wear and tear. Fractures or other joint injuries can lead to OA later in life. This includes injuries to the cartilage and ligaments in joints. Jobs involving kneeling or squatting for more than an hour a day have the highest risk of the development of OA. Jobs that involve lifting, climbing stairs, or walking increase the risk of this disease. Playing sports that involve direct impact on the joint (such as football), twisting (such as basketball or soccer), or throwing also increase the risk of OA.
Medical conditions such as hemophilia can also lead to OA because of bleeding in the joint. Disorders that block the blood supply near a joint lead to avascular necrosis. Other types of arthritis, such as chronic gout, pseudogout, or rheumatoid arthritis lead to “secondary” OA. Systemic diseases also are associated with the development of secondary OA, such as Wilson’s disease and hemochromatosis. Hemochromatosis may cause chondrocalcinosis with secondary OA in many joints, especially with a predilection for the second and third metacarpophalangeal joints. OA of non-weight-bearing joints is almost always the result of secondary OA with the exception of some hand joints.
Classification of Osteoarthritis
Primary or idiopathic OA is divided into localized or generalized forms of the disease. Localized OA most commonly affects the hands, feet, knees, hips, and spine. Generalized OA consists of involvement of three or more joint sites. In secondary OA, specific conditions may cause or enhance the risk of developing OA as mentioned above. Secondary OA may also result from trauma, congenital or developmental disorders, septic arthritis, Paget disease of bone, and other diseases such as diabetes mellitus, acromegaly, hypothyroidism, or neuropathic (Charcot) arthropathy.
Clinical Manifestations
Spine. The cervical and lumbar spine is commonly affected. Spinal involvement in OA is most common at C5, T8, and L3, which represent the areas of greatest spinal flexibility. Two syndromes of clinical importance are due to OA of the lumbar apophyseal joints.22 In the cervical spine, osteophytes arising from the margins of a vertebral body (cervical spondylosis) may compromise the spinal canal. When sufficiently advanced, cervical spinal cord compression may result. Uncovertebral osteophytes can compromise the neural foramen and impinge on the exiting nerve root. Lumbar apophyseal osteophytes (lumbar spondylosis) can cause spinal stenosis if they encroach into the intervertebral foramina and/or the spinal canal. The resultant symptoms of low back pain radiating to the lower extremity worsens with exertion, thereby mimicking vascular claudication, but resolves more rapidly with rest. Spondylolisthesis, a slipping of one vertebral body on another, typically affecting the apophyseal joints at L4 to L5, may occur with severe OA. Diffuse idiopathic skeletal hyperostosis (DISH) is a syndrome of inappropriate bone formation at the insertions and along the course of ligaments and tendons. Although osteoarthritis is frequently present in patients with the DISH syndrome, the latter is thought to represent a distinct clinical entity.
Hands: Osteoarthritic enlargements of the distal and proximal interphalangeal joints are referred to as Heberden’s and Bouchard’s node, respectively. The first carpometacarpal joint is also a common area affected by OA. Enlargement of this joint causes a squared appearance to the hand.
Hip: Pain around the hip is common in patients with OA. It may be due to OA of the hip or to pain referred to the hip area from other structures, such as the lumbosacral spine. Similarly, OA of the hip may result in pain that is referred to distant structures (such as the knee).22 Another potential diagnostic problem is that patients frequently confuse the pain of greater trochanteric bursitis with OA of the hip. The pain from bursitis is felt laterally and does not limit motion; by comparison, OA of the hip is associated with pain in the groin and upper posterior buttock with limited range of motion.
Knee: Osteophytes, effusions, crepitus, and limitation of range of motion are all common signs of OA of the knee. However, findings on physical examination alone may underestimate the degree of knee involvement. In advanced cases, malalignment may be apparent (genu varus or genu valgus), particularly when medial and lateral compartments are affected unequally. Cartilage loss due to OA usually begins in the medial aspect of the tibiofemoral joint; as a result, varus angulation (“bow-legged”) occurs more commonly than valgus (“knock-kneed”). Femorotibial malalignment may be a risk factor for more rapid progression of OA of the knee. A fluctuant swelling along the posterior aspect of the knee, or popliteal (Baker’s) cyst, is a common complication. Involvement of the patellofemoral portions of the joint may be affected by malalignment.22
Feet: The first metatarsophalangeal joint often is affected by OA, resulting in hallux valgus or hallux rigidus. Involvement of the subtalar joint may be particularly troublesome during ambulation; pain is often elicited by inversion and eversion of the foot.22
Uncommonly Affected Joints: Shoulder OA is almost always secondary OA. Symptoms of a diseased glenohumeral joint typically include anterior shoulder pain that gradually worsens over years and that is aggravated by movement. Involvement of the acromioclavicular joint may cause vague shoulder pain, which may present a diagnostic dilemma. Osteophytes located along the undersurface of the acromioclavicular joint may result in rotator cuff tendinitis or tears due to the juxtaposition of tendons with the inferior portion of the acromioclavicular joint. The shoulder may rapidly deteriorate because of an aggressive form of OA that occurs in association with calcium crystalline disease.22 The wrist and elbow may also be affected.
Symptoms
Pain is the principal symptom associated with OA, typically exacerbated by activity and relieved by rest. With more advanced disease, pain may be felt with progressively less activity, eventually occurring at rest and at night. Episodic increases in pain and inflammation suggest synovitis caused by crystalline disease or trauma. Some patients ascribe fluctuating symptoms to changes in the weather, but the evidence for effects of varying barometric pressure, precipitation, and outdoor temperature is conflicting. Pain in OA is not caused directly by cartilage damage since cartilage is aneural. As a result, osteoarthritic radiologic changes are often incidentally noted in patients without symptoms at affected sites. Two general types of pain stimuli in synovial joints can be distinguished: mechanical stimuli, generated by mechanical changes in the environment of the joint (i.e., by direct trauma) and chemical stimuli resulting from tissue inflammation. Stiffness is also a common complaint in patients with OA. Morning stiffness typically resolves in less than 30 minutes after a patient awakens, but may recur following periods of inactivity.
Findings on Physical Examination
Crepitus is a common finding and is probably due to the disruption of the normally smooth articulating surfaces of the joints. Bony enlargement and osteophytes may be palpable as nodules along the periphery of the joint. Tenderness to palpation of involved joints may be evident with or, more often, without associated signs of inflammation. There may also be decreased range of motion and joint malalignment.
Differential Diagnosis:
- Calcium pyrophosphate crystal deposition disease (CPPD disease) — Osteoarthritis of non-weight-bearing joints except the distal interphalangeal joint and proximal interphalangeal joints of the hands is most frequently CPPD disease. Involvement of the second and third metacarpophalangeal (MCP) joints of the hands with OA and the presence of chondrocalcinosis on X-rays of especially knees, the triangular cartilage of the wrist, hips, shoulders, symphasis pubis, and MCPs is frequently due to CPPD disease.
- Rheumatoid arthritis — Unlike OA, rheumatoid arthritis is primarily an inflammatory joint disease with symmetrical joint involvement, and X-ray findings of marginal erosions of joints and juxta-articular osteoporosis. It is a systemic disease involving more organ systems than just joints.
- Infectious monoarticular disease — if only one joint is inflamed, arthrocentesis should be performed to rule out infection.
- Most other forms of arthritis — can end up with OA as the final common pathway for joint damage.
Diagnosis: An essential component to the diagnosis is the correct attribution of signs and symptoms to the affected site. As an example, pain and other symptoms resulting from OA can be confused with soft tissue processes such as bursitis at periarticular sites. Additionally, pain in a particular area may be referred from OA at other sites or may be due to a nonarticular process.
Joint pain is a nonspecific symptom, resulting from many possibilities. The physical examination should evaluate the symptomatic joint and adjacent structures. Imaging, as discussed below, is not always necessary. In selected patients, laboratory tests looking for an alternative diagnosis may be useful: serology for rheumatic arthritis and other rheumatologic disease, serum uric acid for gout, and analysis of joint fluid for infection or crystal-induced arthritis.
Certain clinical features are more suggestive of idiopathic OA than other disorders. As an example, OA does not affect all joints equally; it has a predilection for the fingers, knees, hips, and spine, and rarely affects the elbow, wrist, and ankle. If the atypical joints are involved in a patient suspected of having OA, the clinician should initiate a search for secondary causes of the disorder. The joints are usually asymmetrically involved in OA (particularly the large joints), and a synovial effusion, if present, most commonly has mild inflammatory characteristics (i.e., synovial WBC < 2000/mm3).
Imaging: Imaging can assist by refuting other diagnoses when the clinical picture from history and physical examination leaves this diagnosis unclear.23 However, the diagnosis is a clinical one made by assessing the constellation of presenting clinical features. Plain radiographs are helpful in assessing for the presence and severity of OA. Radiographic changes in OA are insensitive, particularly with early disease, and correlate poorly with symptoms. When present, however, the specificity of the radiographic changes of OA often renders further diagnostic imaging unnecessary. The major radiographic features of OA include (see Figure 1):
- Joint space narrowing;
- Subchondral sclerosis;
- Osteophytes;
- Subchondral cysts.
The clinical relevance of each radiographic finding in OA appears to vary by joint. Minimal joint space of the hip is most closely correlated with hip pain, while osteophytes arising from the patellofemoral and tibiofemoral joints of the knee correlate best with knee pain. Knee joint space narrowing best predicts disease progression.
Magnetic Resonance Imaging (MRI): MRI is not necessary for most patients with suggestive symptoms of OA and/or typical plain radiographic features. However, MRI of the knee has a diagnostic role in patients with joint pain and symptoms such as locking, popping, or instability that suggest meniscal or ligamentous damage. MRI can facilitate the diagnosis of other causes of knee pain that can be confused with osteoarthritis (e.g., osteochondritis dissecans, avascular necrosis, etc.). The presence of a meniscal tear viewed by MRI in a person with knee osteoarthritis is not necessarily a cause of increased symptoms.23 The presence of two MRI findings concomitantly correlates with painful OA of the knee; partial or full-thickness cartilage defects, and bone marrow “edema” as indicated by decreased T1 and increased T2 signal from the subchondral bone. In contrast, marrow edema alone does not appear to be closely associated with knee pain in patients with generalized osteoarthritis.
Management of Osteoarthritis
The management goals for patients with osteoarthritis include patient education about the disease and its therapy, pain control, improving function, and decreasing disability. Optimal management of OA requires a combination of nonpharmacological and pharmacological modalities.
Nonpharmacologic Therapy
Nonpharmacologic therapies for OA of the knee for which there is reasonably strong evidence of efficacy include exercise programs, weight loss, and patient education. Nonpharmacologic interventions are generally begun before medications.
Lifestyle Changes:
1. Exercise. A pivotal and frequently ignored aspect of conservative treatment of OA is exercise.24-26 Exercise increases aerobic capacity, muscle strength, and endurance, and also facilitates weight loss.27,28 All individuals capable of exercise should be encouraged to partake in a low-impact aerobic exercise program (walking, biking, swimming, or other aquatic exercise). Quadriceps strengthening exercises lead to improvements in knee pain and function.29-31 Guidelines routinely advocate exercise;21,32-36 however, clinical practice does not often reflect this recommendation.24-26
Staying active and getting exercise help maintain joint and overall movement. Water exercises, such as swimming, are especially helpful. Low load effect exercise, warm-up and stretching prior to exercise, and use of splints for joint immobilization can be of benefit for joint protection and reduction in symptoms. All exercise programs include range of motion and isometric strengthening.
2. Other Lifestyle Recommendations: Obesity management and weight loss if overweight are extremely important. The majority of patients with OA are either overweight or obese. There is good evidence for the efficacy of weight management,27 which is advocated by most OA guidelines. However, in practice, weight management is not frequently implemented.24-26 In patients with OA who are overweight, weight loss of even modest degree may produce improvement in lower extremity joint pain and function. Other methods of unloading an osteoarthritic joint include canes and walkers, which can reduce joint forces at the hip by as much as 50%. A trial of soft, elastic heeled sports shoes or the use of insoles for patients with knee OA diminishes impact loading.
Moist, superficial heat can raise the threshold for pain, produce analgesia by acting on free nerve endings and decrease muscle spasm.37-39 Ultrasound therapy appears to have no proven benefit in treating OA. Superficial cooling decreases muscle spasm and increases the threshold of pain. Data concerning the efficacy of transcutaneous electrical nerve stimulation (TENS) in patients with OA are conflicting.40-42
Eating a healthy, balanced diet is important. Vitamin D supplementation is indicated in patients at high risk for osteoporosis, such as postmenopausal women. Resting affected joints may alleviate pain. Rest is recommended for only short periods of time, typically 12-24 hours for acute pain and inflammation, because prolonged rest may lead to muscle atrophy and decreased joint mobility. Protecting joints may include the use of braces and splints for symptomatic relief for OA of certain joints such as the knee43 and OA of the carpometacarpal and interphalangeal joints of the thumb.44
Physical Therapy:
Physical therapy can help improve muscle strength and the motion of stiff joints, as well as sense of balance. Therapists have many techniques for treating OA. Physical therapy and exercise improve functional outcome and pain in OA by improving flexibility and by strengthening muscles that support the affected joints.45 An appropriate exercise program can safely reverse deficiencies in gait, strength, flexibility, aerobic power, and exercise capacity.
Pharmacologic Therapy
Pain is the most salient clinical feature of OA and has the biggest impact on both the welfare and performance of patients. Pain management is therefore of great importance when managing osteoarthritis. However, it should be realized that treatment aimed at pain reduction does not necessarily treat the underlying primary disease process and may even interfere negatively with it. In fact, it has been suggested that long-term use of nonsteroidal anti-inflammatory drugs might enhance the pathologic process of cartilage degeneration by removing the regulatory role of PGE2 on IL-1 synthesis.46 On the other hand, treatment aimed primarily at pain relief may, through anti-inflammatory actions, also positively affect the articular cartilage by means of inhibition of release of catabolic factors.47
Systemic Treatment of Joint Pain:
There are, at present, no specific pharmacologic therapies that can prevent the progression of joint damage due to OA.
Analgesics: Pain relief is the primary indication for the use of pharmacologic agents in patients with OA who do not respond to nonpharmacologic interventions. In patients with noninflammatory OA, this goal is generally achieved by the administration of a non-opioid, simple analgesic.
Acetaminophen: At doses of up to 3 g/day, acetaminophen is the drug of choice for pain relief in this setting.48,49 Clinical trials found that acetaminophen is superior to placebo, but less effective in relieving pain due to OA of the hip or knee than nonsteroidal anti-inflammatory drugs (NSAIDs).50 Adverse effects of therapeutic doses of acetaminophen are seldom seen. Hepatotoxicity can occur but, at these doses, is primarily seen only in patients who concurrently consume excessive amounts of alcohol. Acetaminophen in doses of 2 g/day or greater can increase the risk for gastrointestinal (GI) complications, including bleeding and perforation, but these complications are not increased at lower acetaminophen doses. Additionally, the risk of GI complications is greater with the combination of acetaminophen and an NSAID than with either alone.51 There is suggestive but not definitive evidence that chronic, especially daily, acetaminophen use has dose-dependent, long-term nephrotoxicity.21
Tramadol: Tramadol alone or in combination with acetaminophen may also be useful when added to ongoing treatment with an NSAID or COX-2 inhibitor.52
Opioid analgesics: Opioid analgesics may be beneficial for short-term use in patients with acute exacerbations of pain. Arguments have also been made for the use of opioids in patients who are not candidates for surgery and who continue to have moderate to severe pain despite being administered NSAIDs or selective cyclooxygenase (COX-2) inhibitors.53 Opioids may also be considered for patients who are at high risk for adverse effects of both selective COX-2 inhibitors and nonselective nonsteroidal anti-inflammatory drugs (NSAIDs).49,54
NSAIDs: NSAIDs are by far the most important class of compounds in this category. NSAIDs may be indicated in patients with noninflammatory OA who fail to respond to acetaminophen or for those with moderate to severe pain. The majority of experience is with oral administration of NSAIDs, although topical preparations are available as well. NSAIDs should be given prior to oral analgesics in patients with inflammatory OA who do not respond to nonpharmacologic interventions.
Oral NSAIDs: NSAIDs are effective pain relievers in OA patients.55 Many different NSAIDs can be used in patients with symptomatic OA, including over-the-counter agents (aspirin, ibuprofen, and naproxen) and prescription drugs. (See Table 1.) There is immense variability in patients’ responses to the different agents in terms of both efficacy and toxicity.56
- Low dose ibuprofen (< 1600 mg/day) may have less serious gastrointestinal side effects.57
- Nonacetylated salicylates (salsalate, choline magnesium trisalicylate), sulindac, and perhaps nabumetone appear to have less renal toxicity.
- The nonacetylated salicylates and nabumetone have less antiplatelet activity.58
- Indomethacin should probably be avoided for long-term use in patients with hip OA since it may be associated with accelerated joint destruction in this setting.59
- Patients at increased risk of gastroduodenal damage who are receiving low-dose aspirin and a COX-2 selective agent may benefit from anti-ulcer prophylaxis.
|
Class |
Agent* |
Elimination |
COX-2 Selectivity |
Low Dose |
Medium Dose |
High Dose |
|
* Standard (immediate) release preparations § Not approved for OA at this dose |
||||||
|
Salicylates |
Aspirin |
0.25 h (as aspirin) 2-6 h (as salicylate) |
Non-selective |
650 mg QID |
650 mg q4h |
900 mg q4h |
|
Diflunisal |
8-12 h |
Non-selective |
250 mg BID |
500 mg BID |
500 mg TID |
|
|
Salsalate |
1 h (as salsalate) 4-16 h (as salicylate) |
Non-selective |
500-750 mg BID |
750 mg TID |
1000 mg TID |
|
|
Propionic Acids |
Fenoprofen |
3 h |
Non-selective |
200-300 mg QID |
600 mg TID-QID |
800 mg QID |
|
Flurbiprofen |
6 h |
Non-selective |
50 mg BID |
50 mg TID-QID |
100 mg TID |
|
|
Ibuprofen |
2 h |
Non-selective |
400 mg TID |
600 mg TID-QID |
800 mg QID |
|
|
Ketoprofen |
2 h |
Non-selective |
25-50 mg TID |
75 mg TID |
100 mg TID |
|
|
Naproxen |
12-17 h |
Non-selective |
250 mg TID |
500 mg BID |
1250 mg/day divided |
|
|
Oxaprozin |
22 h |
Non-selective |
600 mg daily |
1200 mg daily |
1200 mg daily |
|
|
Acetic Acids |
Diclofenac potassium |
2 h |
Non-selective |
50 mg BID |
50 mg TID |
50 mg QID |
|
Diclofenac sodium |
2 h |
Non-selective |
50 mg BID |
75 mg BID |
50 mg QID§ |
|
|
Etodolac |
6 h |
Partially selective |
200 mg TID |
400 mg BID |
1200 mg/day divided |
|
|
Indomethacin |
5 h |
Non-selective |
25 mg BID-TID |
50 mg BID |
50 mg QID |
|
|
Sulindac |
8 h |
Non-selective |
150 mg BID |
200 mg BID |
200 mg BID |
|
|
Oxicams |
Meloxicam |
15-20 h |
Partially selective |
7.5 mg daily |
7.5 mg daily |
15 mg daily |
|
Piroxicam |
50 h |
Non-selective |
10 mg daily |
20 mg daily |
40 mg daily§ |
|
|
Alkanones |
Nabumetone |
24 h |
Partially selective |
1000 mg daily |
1000 mg BID |
1000 mg BID |
|
Coxibs |
Celecoxib |
11 h |
Selective |
200 mg daily |
200 mg BID |
200 mg BID |
Topical NSAIDs: The topical application of NSAIDs may reduce the risk of side effects that are seen with oral use. Topical NSAIDs, such as aspirin and diclofenac, are available as well.
COX-2 Inhibitors: These drugs have at least a 200- to 300-fold selectivity for inhibition of COX-2 over COX-1. However, two selective COX-2 inhibitors, rofecoxib and valdecoxib, were withdrawn from the worldwide market because of an increased risk of serious cardiovascular adverse events associated with their use. Increased cardiovascular risks preclude use of COX-2 selective agents unless the GI risk is very high and the cardiovascular risk is low (e.g., there are no known cardiovascular disease and absence of multiple cardiovascular risk factors). An alternative approach is the use of a nonselective NSAID and a gastroprotective agent such as a proton pump inhibitor or misoprostol. NSAIDs should not be used in combination because of the greater risk of adverse events and the lack of evidence that the use of two or more NSAIDs is associated with improved efficacy. NSAIDs should be avoided in patients with aspirin sensitivity. The selective COX-2 inhibitor, celecoxib, may be less likely to provoke symptoms in aspirin-sensitive reactive airways disease.48
Choice of NSAID: There is no convincing evidence that any of the available NSAIDs is more effective than any other for osteoarthritis of the knee or hip.60,61 Thus, the choice of an NSAID is based upon a variety of other factors including adverse effect profile, cost, type of OA, and frequency of dosage. It is preferable to use an NSAID on a periodic basis in patients with noninflammatory OA since the presence and intensity of symptoms usually vary with time. A short-acting agent is ideal in this setting.48 Continuous therapy is indicated if this regimen does not provide adequate symptom control. Because of the pathophysiology, continuous NSAID therapy works better in patients with inflammatory osteoarthritis.
Factors to be considered when selecting from the available NSAIDs and COX-2 selective agents:
- When NSAID use is considered, the patient should be informed of the potential cardiovascular risk.
- If there is a history of gastroduodenal disease, a selective COX-2 inhibitor may be considered in patients at low cardiovascular risk or a nonselective NSAID can be combined with anti-ulcer prophylaxis.
- A short-acting NSAID is generally used initially. It usually takes about 2-4 weeks to evaluate the efficacy of an NSAID.56
- If there is inadequate control with the initial dose, then the dose should be gradually increased toward the maximum for that drug. The patient’s renal, liver, and bone marrow function should be monitored as the dose is increased. The patient should be educated to monitor for symptoms indicative of side effects.
- If one NSAID is not effective after 2-4 weeks on a maximal dosage, then another NSAID or nonacetylated salicylate could be tried.
Intraarticular Glucocorticoid Injections: Glucocorticoids inhibit inflammatory mediator production by inhibiting phospholipase A2 through the production of anti-phospholipase proteins called lipocortins.62 Because of their mode of action upstream in the arachidonic acid cascade, glucocorticoids not only inhibit COX-1/2 derived mediators (including prostaglandins, thromboxanes, and lipoxins), but also the LOX-derived mediators like leukotrienes. Glucocorticoids are primarily potent anti-inflammatory agents, exerting their analgesic action indirectly via the suppression of inflammation. Intraarticular glucocorticoid injections may be appropriate in patients with OA who have one or a few joints that are painful despite the use of an NSAID, and in patients with monoarticular or pauciarticular inflammatory osteoarthritis in whom NSAIDs are contraindicated.63
Intraarticular glucocorticoid injections are effective for short-term pain relief and can increase quadriceps strength after knee injection.64 Glucocorticoids formulated for intraarticular injection are in crystalline suspension. Steroid crystals rarely may lead to a transient mild flare of synovitis. Common synthetic glucocorticoid suspensions used for intraarticular injection include triamcinolone acetonide, triamcinolone hexacetonide, and microcrystalline methylprednisolone. The amount of these agents generally used depends upon joint size:
- 10 mg for small joints (interphalangeal, metacarpophalangeal, and metatarsophalangeal joints)
- 20 mg for medium-sized joints (wrists, elbows, ankles, and acromioclavicular joints)
- 40 mg for larger joints (shoulders, knees, hips).
Intraarticular Hyaluronans: Hyaluronic acid (HA), also called hyaluronan, is a large unsulphated glycosaminoglycan that consists of repeating units of D-gluronic acid and N-acetylglucosamine. Although HA is supposed to treat the primary disease process, not to provide analgesia, as is the case with corticosteroids or NSAIDs, it reportedly also has some analgesic effect itself.65 In humans, there are various reports on the analgesic effects of HA in OA, but publication bias and flaws in experimental design may have overestimated the beneficial effects in many studies. A meta-analysis showed only a relatively small positive effect of HA application compared with placebo.66
There may be subpopulations of patients with osteoarthritis that respond well to this type of therapy. Commercial hyaluronan preparations currently are available in the United States include sodium hyaluronate.
Glucosamine and Chondroitin: The use of glucosamine and chondroitin for OA has been controversial, and results of randomized trials have varied.67-81 The balance of evidence from high-quality trials has shown little to no evidence of clinically meaningful benefit.67-69
Colchicine: The basis for the use of colchicine in inflammatory OA that is refractory to NSAIDs and/or intraarticular glucocorticoids is that the majority of such patients have evidence of calcium pyrophosphate dihydrate crystals.82 Inflammation is attenuated by colchicine via microcrystal-induced tyrosine phosphorylation.83 Adding colchicine to ongoing NSAID therapy may produce an additional benefit. This was illustrated in a small study in which 36 patients with OA of the knee were randomly assigned to receive nimesulide plus colchicine (0.5 mg twice daily) or nimesulide plus placebo.84 Significantly more patients receiving the NSAID plus colchicine combination had at least 30% improvement in osteoarthritis scores (57.9% vs 23.5%, respectively). In view of these findings, it may be reasonable to use prophylactic colchicine (0.6 mg twice daily) in patients with OA if the patient has frequent acute inflammatory episodes that do not respond well to NSAIDs, intraarticular steroid injections, and/or joint irrigation. Chronic colchicine therapy is generally safe in patients who do not have underlying hepatic or renal disease.
Surgery
Severe cases of OA often need surgery to replace or repair damaged joints. The typical indications for surgery are debilitating pain and major limitation of functions, such as walking, working, or sleeping not controlled by other means.85
Surgical options include:
- Arthroscopic surgery to trim torn and damaged cartilage, the most common orthopedic surgery performed on the knee, has no demonstrable efficacy.86
- Changing the alignment of a bone to relieve stress on the bone or joint (osteotomy)
- Surgical fusion of bones, usually in the spine (arthrodesis)
- Total or partial replacement of the damaged joint with an artificial knee, hip, shoulder, first carpometacarpal, ankle, or elbow joint are regularly done. Currently, the most common indication for knee and hip replacement is OA (approximately 85% of all cases). The general consensus among orthopedic surgeons on indications for joint replacement were (1) severe daily pain and (2) radiographic evidence of joint space narrowing.85 With proper patient selection, good to excellent results can be expected in 95% of patients. The survival rate of the implant is expected to be 95% at 15 years.87 When overall health improvement is used to assess the cost effectiveness of total joint arthroplasty, the hip and knee arthroplasty have similar excellent results.88
Prognosis
The prognosis seems to differ according to the affected joint:89
- Hand OA: Older age appears to be the strongest risk factor for progression.
- Hip OA: Risk factors for progression to total hip replacement include female gender, night pain, and lower baseline functional capacity.
- Knee OA: A higher body mass index and polyarticular arthritis predict radiographic deterioration. Varus or valgus deformity of the knee correlates with later radiographic worsening of OA of the medial and lateral compartments, respectively.90,91
Patients with OA also experience varying degrees of physical disability, and OA can adversely affect quality of life.92,93 Worsening disability may be correlated with coping styles; in particular, avoidance of activity due to pain may lead to muscle weakness that may impact upon joint stability. Exercise may help to prevent such loss of strength and decrease disability.94 Joint laxity, impaired proprioception, greater body mass index, and more severe joint pain were each predictive of subsequent worsening in function in patients with OA of the knee.
Mortality
There are some studies showing OA associated with excess mortality risk, although the exact cause could not be determined.95,96 Risk factors for death included a history of diabetes, cancer, or cardiovascular disease, and the presence of walking disability.
Summary
Several papers document widespread support for OA guidelines, but there are delays in utilization of these standards, particularly of non-pharmacological recommendations, and variance in the application of recommendations by clinicians in different specialty areas.97-101
Although the evidence for many OA treatments is good, the complexity and high number of treatment recommendations available for OA may be a hindrance to use of the guidelines.
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MONOGRAPH: It's important to understand patients who come to the ED with undifferentiated symptoms, including joint pain.
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