INHIBITION OF BONE-RESORPTION BY INORGANIC-PHOSPHATE IS MEDIATED BY BOTH REDUCED OSTEOCLAST FORMATION AND DECREASED ACTIVITY OF MATURE OSTEOCLASTS

High concentrations of inorganic phosphate (P(i)) are known to inhibit bone resorption, although the mechanism(s) underlying this effect is unclear. To investigate whether P(i) can inhibit the formation of osteoclasts we studied the effects of changes in P(i) concentration between 1 and 4 mM on osteoclast-like cell formation in 1 week cultures of mouse bone marrow. Osteoclast-like cells were identified by multinuclearity, positive staining for tartrate-resistant acid phosphatase (TRAP), and contraction in response to calcitonin. Increasing concentrations of P(i) inhibited formation of these cells in a dose-dependent manner. To study effects of P(i) on the bone-resorbing activity of mature osteoclasts we isolated osteoclasts from calcium-deficient egg-laying hens or rat pups and incubated them on sperm whale dentine slices. High P(i) concentrations markedly reduced both the number of resorption pits formed per dentine slice and the mean area of each pit in both avian and mammalian systems. These data indicate that high concentrations of P(i) act on bone directly, both to inhibit generation of new osteoclasts from their precursor cells and to inhibit bone resorption by mature osteoclasts. These effects of extracellular P(i) concentration may play an important modulatory role on bone turnover in vivo and have potential importance in several disease states in which P(i) metabolism is perturbed.