What the gastroenterologist should know about the gastrointestinal safety profiles of bisphosphonates.

Bisphosphonates are widely prescribed to treat Paget's disease of the bone and to prevent and treat osteoporosis. Soon after the release of alendronate, esophagitis and esophageal strictures were encountered, resulting in labeling changes. Subsequent endoscopic studies in normal subjects showed that alendronate also caused gastric erosions and ulcers. Although the clinical significance of these is still uncertain, the anatomic distribution of both the gastric ulcers and esophageal damage is consistent with a topical irritant effect. Recent data also suggest a synergistic ulcerogenic potential of concurrent alendronate and NSAID use. A 70-mg once-weekly dosage form of alendronate has recently been approved and clinical experience with its gastrointestinal tolerability is ongoing. Risedronate, a third-generation bisphosphonate, appears to have less ulcerogenic potential than alendronate, and esophageal stricture has not been reported. Experience with the bisphosphonates provide a paradigm for the critical role of endoscopists in evaluating the gastrointestinal profile of new drugs. As bisphosphonates are more widely prescribed and more types of bisphosphonates are developed, the role of the gastroenterologist is likely to assume even more importance.