Acid-base balance and bone health

Abstract

On a typical Western diet, humans generate metabolic acids which must be excreted, through renal mechanisms, to maintain a stable physiologic systemic pH. Any impairment of kidney function will lead to a fall in systemic pH which is termed metabolic acidosis. During metabolic acidosis, the bone buffers acid (protons) and also releases calcium, a response that has been observed both in vivo and in vitro. Using an in vitro model system of cultured neonatal mouse calvariae we have studied the effect of metabolic acidosis on bone. Acutely there is direct proton-mediated physicochemical release of calcium from bone. There is also sodium and potassium release from the mineral surface in exchange for the hydrogen ions. With metabolic acidosis of longer duration (>24 h), release of bone calcium occurs by a cell-mediated stimulation of bone resorption and inhibition of bone formation. The cell-mediated response to metabolic acidosis involves changes in specific gene expression and is primarily due to a stimulation of endogenous osteoblastic prostaglandin E2 production, leading to production of RANKL and subsequent activation of osteoclastic bone resorption. The initial signaling event in the osteoblast appears to be activation of a specific proton receptor, OGR1. In addition to a net increase in bone resorption, metabolic acidosis has also recently been shown to stimulate production of osteoblastic FGF23. In contrast to metabolic acidosis, respiratory acidosis, due to an increase in the partial pressure of CO2, does not alter proton or calcium flux in bone. As renal function decreases with age, kidneys cannot excrete the daily acid load and this mild metabolic acidosis can lead to a significant decrease in bone mineralization potentially contributing to osteoporosis and fracture.