Introduction
Background
Osteoarthritis (OA) is the most common articular disease worldwide, affecting over 20 million individuals in the United States alone. Its high prevalence entails significant costs to society. Direct costs of osteoarthritis include clinician visits, medications, 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 next few decades, the need for better understanding of osteoarthritis and for improved therapeutic alternatives will continue to grow.
Pathophysiology
Traditionally, osteoarthritis has been considered a disease of articular cartilage. The current concept holds that osteoarthritis involves the entire joint organ, including the subchondral bone and synovium.
Osteoarthritis has always been classified as a noninflammatory arthritis; however, increasing evidence has shown that inflammation occurs as cytokines and metalloproteinases are released into the joint. Therefore, the term degenerative joint disease is no longer appropriate when referring to osteoarthritis.
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) and proximal interphalangeal (PIP) joints of the hands.
Cartilage is grossly affected. Focal ulcerations eventually lead to cartilage loss and eburnation. Subchondral bone formation also occurs, with development of bony osteophytes.
Frequency
United States
Osteoarthritis affects over 20 million individuals in the United States. Based on the radiologic definition of osteoarthritis, more than half of adults older than 65 years are affected.
International
Osteoarthritis is the most common articular disease. Estimates vary among different populations.
Mortality/Morbidity
* The disease progression of osteoarthritis is characteristically slow, occurring over several years or decades.
* Pain is usually the initial and principal source of morbidity in osteoarthritis. The patient can become progressively less active, leading to morbidities related to decreasing physical activity (including potential weight gain).
Race
The prevalence of osteoarthritis differs among different ethnic groups. Knee osteoarthritis appears to be more common in African American women than in other groups.
Sex
* The likelihood of developing osteoarthritis increases with age. The disease is equally common among men and women aged 45-55 years. After age 55 years, the disease becomes more common in women.
* DIP and PIP joint involvement that results in Heberden and Bouchard nodes is more common in women.
Age
* Osteoarthritis can be defined epidemiologically (ie, using radiographic criteria) or clinically (eg, radiography findings plus clinical symptoms). Based on radiographic criteria, osteoarthritis occurs in 30% of affected individuals aged 45-65 years and in more than 80% by their eighth decade of life, although most are asymptomatic.
Clinical
History
* Pain
o Pain is the main reason persons with osteoarthritis (OA) seek medical attention.
o Initially, symptomatic patients incur pain during activity, which can be relieved by rest and may respond to simple analgesics.
o Morning joint stiffness usually lasts for less than 30 minutes.
o Stiffness during rest (gelling) may develop.
o Joints may become unstable as the osteoarthritis progresses; therefore, the pain may become more prominent (even during rest) and may not respond to medications.
Physical
* Physical examination findings are mostly limited to the affected joints.
o Malalignment with a bony enlargement (depending on the disease severity) may occur.
o Most cases of osteoarthritis do not involve erythema or warmth over the affected joint(s); however, an effusion may be present.
o Limitation of joint motion or muscle atrophy around a more severely affected joint may occur.
* Sources of pain in osteoarthritis include the following:
o Joint effusion and stretching of the joint capsule
o Increased vascular pressure in subchondral bone
o Torn menisci
o Inflammation of periarticular bursae
o Periarticular muscle spasm
o Psychological factors
o Crepitus (a rough or crunchy sensation) may be palpated during motion of an involved joint.
Causes
* Risk factors of osteoarthritis include the following:
o Increasing age
o Obesity
o Female sex
o Trauma
o Infection
o Repetitive occupational trauma
o Genetic factors
o History of inflammatory arthritis
o Neuromuscular disorder
o Metabolic disorder
* The etiopathogenesis of osteoarthritis has been divided into the following 3 stages:
o Stage 1: Proteolytic breakdown of the cartilage matrix occurs. Chondrocyte metabolism is affected, leading to an increased production of enzymes, which includes metalloproteinases (eg, collagenase, stromelysin) that destroy the cartilage matrix. Chondrocytes also produce protease inhibitors, including tissue inhibitors of metalloproteinases (TIMP) 1 and 2 but in amounts insufficient to counteract the proteolytic effect.
o Stage 2: This stage involves the fibrillation and erosion of the cartilage surface, with a subsequent release of proteoglycan and collagen fragments into the synovial fluid.
o Stage 3: The breakdown products of cartilage induce a chronic inflammatory response in the synovium. Synovial macrophage production of cytokines, such as interleukin 1 (IL-1), tumor necrosis factor-alpha, and metalloproteinases, occurs. These can diffuse back into the cartilage and directly destroy tissue or stimulate chondrocytes to produce more metalloproteinases. Other pro-inflammatory molecules (eg, nitric oxide [NO], an inorganic free radical) may also be a factor. Eventually, these events alter the joint architecture, and compensatory bone overgrowth occurs in an attempt to stabilize the joint. As the joint architecture is changed and further mechanical and inflammatory stress occurs on the articular surfaces, the disease progresses unchecked.Differential Diagnoses
Rhinosporidiosis
Other Problems to Be Considered
Osteoarthritis (OA) can usually be diagnosed on clinical grounds. The history and physical examination findings are sufficient. Radiographic findings confirm the initial impression (see Imaging Studies), and laboratory values are typically within the reference range. The initial goal is to differentiate osteoarthritis from other arthritides (eg, rheumatoid arthritis).
Rheumatoid arthritis predominately affects the wrists and the metacarpophalangeal (MCP) and PIP joints. Rheumatoid arthritis rarely, if ever, involves the DIP joints or lumbosacral spine. Rheumatoid arthritis is associated with prominent prolonged (>1 h) morning stiffness. Radiographic findings of rheumatoid arthritis include bone erosion (eg, periarticular osteopenia, marginal erosions of bone) rather than formation. Laboratory findings that further differentiate rheumatoid arthritis include systemic inflammation, positive rheumatoid factor results, joint fluid with polymorphonuclear cell predominance, and a substantially elevated WBC count.
Clinical history and characteristic radiographic findings can be used to differentiate spondyloarthropathy from sacroiliac and lumbosacral spine involvement.
Secondary osteoarthritis must be considered in individuals with chondrocalcinosis, joint trauma, metabolic bone disorders, hypermobility syndromes, and neuropathic diseases.
Reactive arthritis is another problem that may be considered.
Workup
Laboratory Studies
* No specific laboratory abnormalities are associated with osteoarthritis (OA).
o Levels of acute-phase reactants and erythrocyte sedimentation rate are within the reference range.
o Synovial fluid analysis usually indicates a WBC count below 2000/µL with a mononuclear predominance.
Imaging Studies
* Radiography
o Conduct imaging studies of the affected joint.
o The presence of osteophytes (ie, spurs at the joint margins) is the most characteristic findings.
o Other findings in osteoarthritis include asymmetric joint-space narrowing, subchondral sclerosis, and subchondral cyst formation.
o Roentgenographic findings are often poor predictors of the degree of symptomatology in a particular patient.
Procedures
Arthrocentesis of the affected joint can help exclude inflammatory arthritis, infection, and/or crystal arthropathy.
Histologic Findings
Histologically, the earliest changes occur in the cartilage. Proteoglycan staining is diminished, and, eventually, irregularity of the articular surface with clefts and erosions occurs.Treatment
Medical Care
Nonpharmacologic interventions are the cornerstones of osteoarthritis (OA) therapy and include patient education, temperature modalities, weight loss,1 exercise, physical therapy, occupational therapy, and joint unloading in certain joints (eg, knee, hip).
* Reduction of joint stress
o Instruct the patient to avoid aggravating stress to the affected joint.
o Implement correction procedures if the patient illustrates poor posture.
o Encourage obese patients to lose weight, thus relieving stress on the affected knees or hips.
o Occupational adjustments may be necessary.
* Physical therapy
o Osteoarthritis of the knee may result in disuse atrophy of the quadriceps. These muscles help protect the articular cartilage from further stress.
o Instruct the patient to perform aerobic and muscle-strengthening exercises.
o Chaipinyo and Karoonsupcharoen (2009) found no significant difference between home-based strength training and home-based balance training for knee pain caused by osteoarthritis. However, more improvement was noted in the strength group in terms of knee-related quality of life (improved 17 points out of 100 [95% CI, 5-28] more than the balance group).2
o Hydrotherapy may be beneficial.
o Some patients with osteoarthritis benefit from heat and capsaicin cream placed locally over the affected joint, and a minority of patients report relief with ice.3
* Pharmacologic therapy
o The goals of osteoarthritis treatment include pain alleviation and improvement of functional status. Presently, no practical medication-based disease or structure-modifying intervention has been proven.
o Begin treatment with acetaminophen for mild or moderate pain without apparent inflammation.
o If the clinical response to acetaminophen is not satisfactory or if the clinical presentation is inflammatory, consider nonsteroidal anti-inflammatory drug (NSAIDs). Use the lowest effective dose or intermittent dosing if symptoms are intermittent and then try full doses if the patient's response is insufficient.
o Options in patients at an elevated risk for GI toxicity due to NSAIDs include the addition of a proton-pump inhibitor or misoprostol to the treatment regimen or the use of a selective cyclooxygenase inhibitor instead of the nonselective NSAID.
o In patients with highly resistant pain, consider the analgesic tramadol.
o Muscle relaxants may benefit patients with evidence of muscle spasm.
o Contemplate intra-articular injections of glucocorticoids to improve symptoms. No more than 4 glucocorticoid injections should be administered to a single joint per year because of the risk of long-term damage to cartilage. Systemic glucocorticoids have no role in the management of osteoarthritis. Intra-articular injections of hyaluronic acid (HA) are approved as symptomatic therapy of osteoarthritis in the knee. Prescribe as a series of 3 or 5 injections (depending on the product). Each injection is administered one week apart.
o Judicious use of narcotics (eg, acetaminophen with codeine) is reserved for patients with severe osteoarthritis.
Surgical Care
* Joint lavage: Closed-needle joint lavage may benefit a small subgroup of patients with osteoarthritis. However, a 2010 meta-analysis of randomized controlled trials of joint lavage for knee osteoarthritis suggests that, at 3 months, joint lavage alone does not significantly relieve pain or improve function. In addition, the combination of joint lavage and intra-articular steroids injection is no more effective than lavage alone. In their review of 6 trials including 855 patients, Avouac et al found that the pooled effect size (ES) of joint lavage versus placebo was not significant for pain intensity (ES = 0.17 [-0.37, 0.71]) or physical function (ES = -0.15 [-0.34, 0.04]). Likewise, the pooled ES of joint lavage combined with steroid injection versus joint lavage alone was not significant for pain intensity (ES = -0.82 [-2.47, 0.82]) or physical function (ES = 0.09 [-0.28, 0.45]).4
* Arthroscopy: Arthroscopy may help patients with osteoarthritis of the knee that in whom imaging reveals specific structural damage (eg, for repairing meniscal tears, removing fragments of torn menisci that are producing symptoms). Overall, arthroscopy is not recommended for nonspecific "cleaning of the knee" in osteoarthritis.
* Osteotomy
o Consider this procedure in patients with a malaligned hip or knee joint.
o The procedure is usually recommended in younger patients with osteoarthritis.
o Osteotomy can lessen the pain, although it can lead to more challenging surgery later if the patient requires arthroplasty.
* Arthroplasty
o Perform this procedure 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.
o This procedure alleviates pain and may improve function. Approximately 8-15 years of viability are expected from the joint replacement in the absence of complications.
Consultations
* A physiatrist may help in formulating a nonpharmacologic management plan.
* A referral to an orthopedic surgeon may be necessary if the osteoarthritis fails to respond to a medical management plan.
* A nutritionist may help the patient lose weight.
Diet
A diet to achieve some degree of weight loss may be beneficial.
Activity
Osteoarthritis may severely hinder the patient's ability to work or even to perform daily living activities, depending on the joints involved and the degree of involvement.
Medication
The goals of pharmacotherapy are to reduce morbidity and to prevent complications. Pay careful attention to a particular pharmacologic regimen's adverse-event profile.
Analgesic agents
Pain control is essential in the management of osteoarthritis (OA). The goals of treatment include pain alleviation and improvement of functional status. Currently, disease/structure-modifying intervention has been proven
Acetaminophen (Tylenol, Panadol, Aspirin-Free Anacin)
Initial trial warranted in patients with mild-to-moderate symptoms from osteoarthritis who fail to get sufficient relief with nonpharmacologic measures. DOC for patients with documented hypersensitivity to aspirin or NSAIDs, history of upper GI disease, or on anticoagulants.
* Dosing
* Interactions
* Contraindications
* Precautions
Adult
1000 mg PO tid/qid; not to exceed 4 g/d
Pediatric
Disease state not seen in pediatrics
* Dosing
* Interactions
* Contraindications
* Precautions
Rifampin may reduce analgesic effects; coadministration with barbiturates, carbamazepine, hydantoins, and isoniazid may increase hepatotoxicity
* Dosing
* Interactions
* Contraindications
* Precautions
Documented hypersensitivity
* Dosing
* Interactions
* Contraindications
* Precautions
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Hepatotoxicity can occur with various dose levels in persons with chronic alcoholism; severe or recurrent pain or high or continued fever may indicate a serious illness; contained in many OTC products, and combined use with these products may result in cumulative doses exceeding recommended maximum dose/d
Nonsteroidal anti-inflammatory drugs (NSAIDs)
These agents have analgesic, anti-inflammatory, and antipyretic activities. They are used for to relieve osteoarthritis pain when the clinical response is unsatisfactory to acetaminophen. The mechanism of action is nonselective inhibition of cyclooxygenases 1 and 2, resulting in reduced synthesis of prostaglandins and thromboxanes. Other mechanisms may also exist, such as inhibition of leukotriene synthesis, lysosomal enzyme release, lipoxygenase activity, neutrophil aggregation, and various cell-membrane functions.
In more inflammatory presentations of osteoarthritis, such as knee involvement with effusion, these agents may be used as first-line pharmacologic therapy.
Use the lowest effective dose or intermittent therapy if symptoms are intermittent.
Patients at high risk for GI toxicity may consider adding misoprostol or a proton pump inhibitor to the regimen or substituting a COX-2–specific inhibitor for the NSAID.
Ibuprofen (Ibuprin, Advil, Motrin)
Relieves pain and inflammation. Widely available. Relatively inexpensive as a generic drug.
* Dosing
* Interactions
* Contraindications
* Precautions
Adult
400 mg PO tid prn; not to exceed 2400 mg/d
Pediatric
Disease state not seen in pediatrics
* Dosing
* Interactions
* Contraindications
* Precautions
May decrease effects of loop diuretics; coadministration of anticoagulants may increase PT (monitor and watch for signs of bleeding); may increase serum lithium levels and risk of methotrexate toxicity; probenecid may increase toxicity of NSAIDs
* Dosing
* Interactions
* Contraindications
* Precautions
Documented hypersensitivity to ibuprofen, other NSAIDs, or aspirin; avoid in peptic ulcer disease, recent GI bleeding or perforation, renal insufficiency, and high risk of bleeding
* Dosing
* Interactions
* Contraindications
* Precautions
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Caution in congestive heart failure, hypertension, decreased renal and hepatic function, anticoagulation abnormalities, or during anticoagulant therapy; adjust dose in renal insufficiency
Black Box Warning
NSAIDs may increase risk of serious cardiovascular thrombotic events, MI, and stroke, which can be fatal; NSAIDs also increase risk of serious adverse GI effects, including stomach or intestinal bleeding, ulceration, and perforation, which can be fatal; elderly patients are at greater risk for serious GI events
Meloxicam (Mobic)
To some extent, more selective for COX-2 receptors, compared to traditional NSAIDs. Decreases activity of cyclooxygenase, which in turn inhibits prostaglandin synthesis. These effects decrease formation of inflammatory mediators.
* Dosing
* Interactions
* Contraindications
* Precautions
Adult
7.5 mg PO qd prn; may increase to 15 mg PO qd prn
Pediatric
Not established
* Dosing
* Interactions
* Contraindications
* Precautions
Coadministration with aspirin increases risk of inducing serious NSAID-related adverse effects; probenecid may increase concentrations and, possibly, toxicity of NSAIDs; may decrease effect of hydralazine, captopril, and beta-blockers; may decrease diuretic effects of furosemide and thiazides; may increase PT when taking anticoagulants (instruct patients to watch for signs of bleeding); may increase risk of methotrexate toxicity; phenytoin levels may be increased when administered concurrently
* Dosing
* Interactions
* Contraindications
* Precautions
Documented hypersensitivity; active GI bleeding
* Dosing
* Interactions
* Contraindications
* Precautions
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Acute renal insufficiency, hyperkalemia, hyponatremia, interstitial nephritis, and renal papillary necrosis may occur; increases risk of acute renal failure in patients with preexisting renal disease or compromised renal perfusion; reversible leukopenia may occur, (discontinue if there is persistent leukopenia, granulocytopenia, or thrombocytopenia)
Black Box Warning
NSAIDs may increase risk of serious cardiovascular thrombotic events, MI, and stroke, which can be fatal; NSAIDs also increase risk of serious adverse GI effects, including stomach or intestinal bleeding, ulceration, and perforation, which can be fatal; elderly patients are at greater risk for serious GI events
Esomeprazole and naproxen (Vimovo)
Naproxen component is indicated for relief of signs and symptoms of osteoarthritis, rheumatoid arthritis, and ankylosing spondylitis. Naproxen is an NSAID that inhibits inflammatory reactions and pain by decreasing activity of cyclo-oxygenase, which is responsible for prostaglandin synthesis.
Esomeprazole component is indicated to decrease risk of gastric ulcers in patients at risk of developing NSAID-associated gastric ulcers. Esomeprazole is the S-isomer of omeprazole, a proton pump inhibitor. Inhibits gastric acid secretion by inhibiting H+/K+-ATPase enzyme system at secretory surface of gastric parietal cells.
* Dosing
* Interactions
* Contraindications
* Precautions
Adult
1 tab PO bid at least 30 min ac
Delayed-release tab; swallow whole and do not chew, crush, dissolve, or split
Available in 2 dosage strengths: Esomeprazole 20 mg and naproxen 375 mg per tab or esomeprazole 20 mg and naproxen 500 mg per tab
Pediatric
<18 years: Not established
* Dosing
* Interactions
* Contraindications
* Precautions
Concomitant use of NSAIDs may reduce antihypertensive effect of ACE inhibitors, diuretics, and beta-blockers; NSAIDs increase lithium plasma levels; concomitant use with methotrexate may increase methotrexate toxicity; concomitant use with warfarin may result in increased risk of bleeding complications (monitor INR and prothrombin time); esomeprazole inhibits gastric acid secretion and may interfere with absorption of drugs for which gastric pH is an important determinant of bioavailability (eg, ketoconazole, iron salts, digoxin, atazanavir, nelfinavir); esomeprazole inhibits CYP2C19 and therefore may alter serum levels/activity of CYP2C19 substrates; esomeprazole is extensively metabolized by CYP2C19 and CYP3A4
* Dosing
* Interactions
* Contraindications
* Precautions
Documented hypersensitivity; NSAIDs are contraindicated for perioperative pain in the setting of coronary artery bypass graft surgery (increased risk of MI and stroke); NSAIDs are contraindicated during late pregnancy (risk of premature closure of ductus arteriosus)
* Dosing
* Interactions
* Contraindications
* Precautions
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Black Box Warning
NSAIDs may increase risk of serious cardiovascular thrombotic events, MI, and stroke, which can be fatal; NSAIDs also increase risk of serious adverse GI effects, including stomach or intestinal bleeding, ulceration, and perforation, which can be fatal; elderly patients are at greater risk for serious GI events
Precautions
May cause anaphylactoid reaction; not recommended with severe hepatic impairment or moderate-to-severe renal impairment; common adverse effects (>5%) include erosive gastritis, dyspepsia, gastritis, diarrhea, gastric ulcer, upper abdominal pain, and nausea
COX-2 inhibitors
Although increased cost can be a negative factor, the incidence of costly and potentially fatal GI bleeds is less in nonaspirin users receiving COX-2 inhibitors than with traditional NSAIDs.
Celecoxib (Celebrex)
COX-2–specific inhibitor. At therapeutic concentrations, COX-2 (inducible by cytokines at sites of inflammation such as the joints) is inhibited and COX-1 isoenzyme (present in platelets and GI tract) is spared; therefore, in nonaspirin users, incidence of GI toxicity, such as endoscopic peptic ulcers, bleeding ulcers, perforations, and obstructions, is decreased when compared to nonselective NSAIDs. COX-2 is expressed in the kidney; however, the renal safety profile is not significantly superior to that of NSAIDs.
* Dosing
* Interactions
* Contraindications
* Precautions
Adult
100 mg PO bid or 200 mg PO qd
Pediatric
Disease state not seen in pediatricsFollow-up
Deterrence/Prevention
* Overweight patients who have early signs of osteoarthritis (OA) or who are at high risk should be encouraged to lose weight.
* Recommend quadriceps-strengthening exercises in patients with osteoarthritis of the knees, except in those with pronounced valgus or varus deformity at the knees.
Prognosis
The prognosis of osteoarthritis depends on joints involved and severity. No proven disease/structure-modifying drugs for osteoarthritis currently exist; thus, the medication-based regimen is directed at symptom relief.
Patient Education
* Educate the patient on the natural history of and management options for osteoarthritis. Explain the differences between osteoarthritis and other more rapidly progressive arthritides such as rheumatoid arthritis.
* For excellent patient education resources, visit eMedicine's Arthritis Center. Also, see eMedicine's patient education article Osteoarthritis.
Miscellaneous
Medicolegal Pitfalls
* The risk of medications used to treat osteoarthritis (OA) include, but are not limited to, GI toxicities and potential cardiac toxicities of NSAIDs and potential complications of arthrocentesis. Discuss these risks with the patient.
* Complete a procedure note in the patient's chart for each arthrocentesis.
