Section Review: Oncologic, Endocrine & Metabolic: The vacuolar H⁺-ATPase: A potential target for drug development in bone diseases

Abstract

Osteoporosis and other skeletal or joint disorders involve an increased bone resorption by osteoclasts. Acidification of the bone resorbing compartment, which underlies osteoclasts at their site of attachment to the bone matrix, is of critical importance and results from the activity of vacuolar proton ATPases present in the osteo-clast's plasma membrane. In this review, we discuss the possibilities of therapeutic intervention by drugs targeted toward these proton transport systems, potentially resulting in decreased bone resorption in vitro and in vivo. The mechanisms of action of various inhibitors of the osteoclast vacuolar proton pump are discussed in the context of the current structural and functional knowledge of vacuolar-type proton ATPases.