Acid and base effects on avian osteoclast activity

Osteoclasts generate a massive acid flux to mobilize bone calcium. Local extracellular acidification by polarized vacuolar-type H⁺-ATPase, balanced by contralateral HCO₃/^--Cl^- exchange to maintain physiological intracellular pH, is theorized to drive this process. It follows that extracellular pH, PCO₂, or HCO₃/^- concentration ([HCO₃/^-]) should impact bone matrix dissolution. However, the effects on bone resorption of the concentrations of these ions or their transmembrane gradients are unknown. Furthermore, because bone management is a vital process, regulatory feedback may minimize such effects. Thus a complex relationship between bone resorption and pH, PCO₂, and [HCO₃/^-] is expected but requires experimental determination. We measured bone resorption by isolated avian osteoclasts while varying these parameters across the physiological range. Bone degradation increased 50% from pH 7.3 to 6.7, whether achieved by changing [HCO₃/^-] (2.3-38 mM) at constant HCO₃ or PCO₂ (15-190 mmHg) at constant [HCO₃/^-]. However, at constant pH, changing PCO₂ and [HCO₃/^-] within physiological limits did not affect bone resorption. In contrast, total HCO₃ removal at pH 7.4 reduced bone degradation by rat or avian osteoclasts substantially, confirming that normal acid secretion requires HCO₃/^-. These observations support a model coupling osteoclastic bone resorption to proton and HCO₃/^- transport but indicate that [HCO₃/^-] is not rate limiting under physiological conditions. Extracellular pH changes affect osteoclastic bone resorption measurably, but not dramatically, at physiological [HCO₃/^-].