Metabolic alkalosis decreases bone calcium efflux by suppressing osteoclasts and stimulating osteoblasts

In vivo and in vitro evidence indicates that metabolic acidosis, which may occur prior to complete excretion of end products of metabolism, increases urinary calcium excretion. The additional urinary calcium is almost certainly derived from bone mineral. Neutralization of this daily acid load, through the provision of base, decreases calcium excretion, suggesting that alkali may influence bone calcium accretion. To determine whether metabolic alkalosis alters net calcium efflux (J(Ca)(+)) from bone and bone cell function, we cultured neonatal mouse calvariae for 48 h in either control medium (pH approximate to 7.4, [HCO3-] approximate to 24), medium simulating mild alkalosis (pH approximate to 7.5, [HCO3-] approximate to 31), or severe alkalosis (pH approximate to 7.6, [HCO3-] approximate to 39) and measured J(Ca)(+), and the release of osteoclastic beta-glucuronidase and osteoblastic collagen synthesis. Compared with control, metabolic alkalosis caused a progressive decrease in J(Ca)(+), which was correlated inversely with initial medium pH (pH(i)), Alkalosis caused a decrease in osteoclastic beta-glucuronidase release, which was correlated inversely with pH(i) and directly with J(Ca)(+). Alkalosis also caused an increase in osteoblastic collagen synthesis, which was correlated directly with pH(i) and inversely with J(Ca)(+). There was a strong inverse correlation between the effects alkalosis on osteoclastic beta-glucuronidase release and osteoblastic collagen synthesis. Thus metabolic alkalosis decreases J(Ca)(+) from bone, at least in part, by decreasing osteoclastic resorption and increasing osteoblastic formation. These results suggest that the provision of base to neutralize endogenous acid production may improve bone mineral accretion.