Chronic PPI use has been associated with fractures and osteoporosis. Although randomized controlled trials have not found an increased risk of fractures, seven epidemiologic studies have been done, six of which have shown increased risk with dose of drug and duration of exposure. Support for this evidence comes from a causal relationship noted between acid suppression and reduced absorption of mineral calcium in the diet.38,39 This has prompted the FDA to recommend that physicians exercise more caution when prescribing PPIs and add safety information about the possible increased risk of hip, wrist, and spine fractures. Three epidemiologic studies, however, have not shown an association with PPI use,40Y42 suggesting that there may be no direct relationship, and those patients who were prescribed PPIs are prone to osteoporosis because of their general health condition.