Grant: Operating Grant

The theoretical "silver-bullet" therapy for pomoting healthier bone is to reduce osteoclastic bone resorption while increasing osteoblastic bone formation. To date, the "gold standard" treatment to prevent bone loss are the bisphosphonates, which do indeed eliminate osteoclasts, but they also prevent the effectiveness of PTH therapies aimed at increasing bone formation. We hypothesize this is due to bisphosphonates eliminating the osteoclast-osteoblast signaling essential for bone formation. By trying to understand the various roles V-ATPases play in osteoclastogenesis and activity, a therapeutic can be developed that would prevent V-ATPases from pumping acid onto bone but would not affect osteoclastogenesis. Osteoclast-osteoblast signaling would remain unaffected and bone formation therapies such as PTHrP could be used in conjunction, allowing for the first time inhibition of bone loss and concurrent stimulation of bone formation.