Test your medicine knowledge with the MKSAP challenge, in partnership with the American College of Physicians.

A 64-year-old man is evaluated for a 2-year history of knee osteoarthritis. He has bilateral knee pain that worsens with walking. He has tried topical therapies, physical therapy, and acetaminophen, none of which has provided relief. The patient also has peripheral vascular disease, hyperlipidemia, and hypertension. Medications are hydrochlorothiazide, pravastatin, and a daily aspirin.

On physical examination, temperature is 37.0 °C (98.6 °F), blood pressure is 116/76 mm Hg, pulse rate is 60/min, and respiration rate is 12/min. BMI is 26. Musculoskeletal examination reveals small knee effusions bilaterally, with crepitus and tenderness along the medial joint line.

Laboratory studies, including complete blood count, erythrocyte sedimentation rate, plasma glucose, and serum creatinine, are normal.

Radiographs of the knees, including weight-bearing studies, reveal bilateral medial joint-space narrowing, subchondral sclerosis, and small osteophytes.

Which of the following is the most appropriate treatment for this patient?

A: Celecoxib
B: Colchicine
C: Indomethacin
D: Prednisone
E: Tramadol

MKSAP Answer and Critique

The correct answer is E: Tramadol.

Treatment with tramadol is indicated for this patient with knee osteoarthritis. Acetaminophen is first-line pharmacologic therapy for osteoarthritis because of its safe profile at approved doses, and it is considered complementary to nonpharmacologic interventions. However, this patient has not responded to acetaminophen in conjunction with physical therapy and topical therapies. Tramadol is a multi-acting agent, and its use in patients with osteoarthritis is well established. This partial opiate agonist also raises serotonin and norepinephrine levels; unlike most opiates, its addictive potential is low, and it does not cause constipation.

Selective cyclooxygenase-2 inhibitors such as celecoxib are useful in the treatment of osteoarthritis but are associated with increased cardiovascular risk in susceptible persons such as this patient who has peripheral vascular disease, hyperlipidemia, and hypertension.

Colchicine has potent anti-inflammatory effects in specific diseases such as gout and familial Mediterranean fever; however, it carries no analgesic potential and is not used to treat osteoarthritis.

Indomethacin is a potent nonselective NSAID with anti-inflammatory effects. Because of its numerous side effects, this agent is not considered first-line therapy in the management of a chronic condition such as osteoarthritis. Its strong association with induction of hypertension and kidney disease makes indomethacin a less desirable agent for this patient. Additionally, indomethacin and most other nonselective NSAIDs are associated with varying degrees of cardiovascular risk and should be employed with caution, especially in high-risk patients. One exception may be naproxen, which in epidemiologic studies has been associated with a lower level of cardiovascular risk and possibly even cardioprotection.

Although corticosteroid injections into the knees may have transient benefit in patients with osteoarthritis, oral prednisone is not standard for osteoarthritis and lacks the analgesic capacity of NSAIDs.

Key Point

• Selective cyclooxygenase-2 inhibitors are associated with increased cardiovascular risk and should be used cautiously in patients with cardiovascular disease.

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