A 68-year-old woman comes to the office due to a burning sensation in her chest and throat for the past 2 weeks. Associated symptoms include trouble swallowing. Medical history is significant for osteoporosis, and she has no known drug allergies. The patient has smoked half a pack of cigarettes daily for 50 years, and does not use alcohol or illicit drugs. Temperature is 36.7 C (98 F), blood pressure is 110/70 mm Hg, and pulse is 70/min. BMI is 20 kg/m². Cardiopulmonary examination shows clear lungs and normal S1 and S2. The abdomen is soft and nontender. Laboratory results are normal. It is determined that the patient's current symptoms are caused by one of her medications, which is discontinued. Her symptoms subsequently resolve. The medication responsible for this patient's presentation is also associated with which of the following side effects?

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11ec160b_3c32_8de5_9249_cdd11b1c52fe_MD0001_00 This patient has esophagitis, with burning pain in the chest and dysphagia. Medication-induced esophagitis is a common adverse effect of bisphosphonates (eg, alendronate, risedronate) thought to be caused by disruption of the protective phospholipid barrier in the lower esophagus. This allows refluxing gastric acid to cause mucosal erosion and ulceration. Bisphosphonates are contraindicated in conditions that impair esophageal motility (eg, stricture, achalasia). When bisphosphonates are used, the risk of esophagitis can be lessened by taking the medication with a full glass of water (to ensure the pill is delivered fully into the stomach) and remaining upright for 30 minutes following administration (to avoid reflux of gastric contents). Bisphosphonates are also associated with osteonecrosis of the jaw (mandible or maxilla) and atypical bone fractures (eg, stress fractures of the subtrochanteric zone and femoral shaft). The precise pathophysiology is debated and may vary, but proposed mechanisms include suppression of bone remodeling, impaired healing of microfractures, and decreased angiogenesis. (Choice A) Medication-induced nephropathy can be due to interstitial nephritis (eg, cyclosporine), crystal nephropathy (eg, acyclovir), renal vasoconstriction (eg, amphotericin B, nonsteroidal anti-inflammatory drugs), or tubular injury (eg, aminoglycosides). Bisphosphonates are eliminated by the kidney and should be used with caution in patients with chronic kidney disease, but do not have substantial nephrotoxicity. (Choice B) Bisphosphonates decrease bone resorption, thus lowering serum calcium levels. They are sometimes used in the treatment of severe hypercalcemia (eg, hypercalcemia of malignancy). (Choice D) Venous thromboembolism is a recognized complication of selective estrogen receptor modulators (eg, raloxifene), but these medications do not often cause esophagitis. Bisphosphonates do not appreciably increase the risk of thromboembolism. (Choice E) Vitamin B₁₂ deficiency can be seen in long-term proton pump inhibitor (eg, omeprazole) therapy, possibly due to decreased acid-dependent cleavage of vitamin B₁₂ from dietary proteins. Although proton pump inhibitors may be taken by patients with bisphosphonate-induced esophagitis, bisphosphonates do not affect vitamin B₁₂ metabolism. Educational objective: Medication-induced esophagitis is a common adverse effect of bisphosphonates. Bisphosphonates are also associated with increased risk of osteonecrosis of the jaw and atypical femoral fractures.

A 68-Year-Old Woman Comes to the Office Due to a Burning