Osteoporotic fractures, particularly hip fractures, can have a devastating impact on the well-being of the elderly population. Recently, two population-based observational studies reported a highly important association between the use of potent acid suppressive therapy and an increased risk of hip fractures. The mechanisms underlying such an association are not clear. However, a careful review of the existing evidence seems to suggest that the main physiologic consequences of proton pump inhibitor therapy may each have a theoretical influence on bone metabolism. Specifically, inhibition of the osteoclastic proton pumps may reduce bone resorption, while profound acid suppression could potentially hamper intestinal calcium absorption, and secondary hypergastrinemia may enhance bone resorption through the induction of parathyroid gland hyperplasia. However, the existing data are clearly too limited for us to draw any definitive conclusions, and more studies are urgently needed to delineate the physiologic relevance of these theoretical mechanistic links, individually and collectively.