Alendronate-associated esophagitis: Endoscopic and pathologic features

INTRODUCTION: Alendronate sodium is an oral aminobiphosphonate used to prevent osteoporosis, that has been associated with esophagitis. We describe the distinctive endoscopic and biopsy findings of alendronate-associated esophagitis. METHODS: We identified five patients on alendronate who had endoscopy to evaluate symptoms. Endoscopic and biopsy findings were reviewed. Fragments of alendronate tablets were examined by standard and polarized light microscopy and compared to material seen in biopsies. CLINICAL FEATURES: Patients with alendronate-associated esophagitis included a 44 year old man, and 4 women from 59 to 79 years old. One had pre-existing esophageal dysmotility. None took special precautions while swallowing alendronate. Presenting symptoms were dysphagia or odynophagia. The duration of alendronate exposure before symptoms was 1 week in 2 patients, and 3, 20 and 28 weeks in the other 3. Symptoms resolved within days of stopping alendronate. One patient was re-exposed to alendronate and again developed symptoms within 1 week. ENDOSCOPIC/BIOPSY FINDINGS: Esophagitis was seen in the distal esophagus only in 1, both middle and distal esophagus in 2, and middle esophagus only in 2 patients. There were broad esophageal erosions and ulcerations. All cases had a distinctive thick white pseudomembranous exudate loosely-adherent to the erosions, that had an appearance suggesting sloughing of mucosa; biopsies showed this material to be a dense leukofibrinous exudate, that usually contained entrapped squamous cells. Biopsies showed actively inflamed granulation tissue in four cases. Two cases had a birefringent crystalline material in biopsies, with a microscopic appearance similar to particles obtained from alendronate tablets. Two cases had endoscopy again 3-4 months after stopping alendronate. No esophagitis was present. One had sheets of membranous tissue loosely adherent to apparently normal esophageal mucosal; biopsies showed this to be a thin layer of squamous mucosa with abundant surface bacteria. The other had a membranous web at the ulcer site, and a sheet of squamous mucosa came loose with minimal trauma during endoscopy. CONCLUSIONS: 1) Alendronate-associated esophagitis often has a distinctive endoscopic appearance with broad erosions and loosely-adherent pseudomembranes made up of a dense leukofibrinous exudate. 2) Alendronate-associated esophagitis is likely due to a topical effect, based on the presence of crystalline material in esophageal biopsies that is similar to material obtained from alendronate tablets. 3) Follow-up endoscopy in two patients suggests that there may be abnormalities of the esophageal mucosa after healing of alendronate-associated esophagitis.