Gastric acidification plays a key role in regulating the proper calcium levels needed to maintain healthy bones. The study, online this week in Nature Medicine, could have implications in the bone condition osteopetrosis as well as for patients on proton pump inhibitors that are used to treat gastrointestinal diseases such as peptic ulcers.

Osteopetrosis is a condition of pathologically high bone mass. In a subset of these patients there is also evidence of osteopetrorickets - brittle bones due to low calcium levels. Recent evidence has pointed to associations of osteopetrosis with mutations in the TCIRG1 gene, which encodes for a subunit of a proton pump that is required for the proper activity of bone-resorbing cells, called osteoclasts. Michael Amling and colleagues show that Tcirg1 mutant mice have an osteopetrorickets phenotype; whereas, historically, mice mutated in other genes that also control osteoclast activity have only an osteopetrosis phenotype, indicating that these two