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 da ily acid load, through the provision of base, decreases calcium excret ion, suggesting that alkali may influence bone calcium accretion. To d etermine whether metabolic alkalosis alters net calcium efflux (J(Ca)( +)) from bone and bone cell function, we cultured neonatal mouse calva riae 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 approximat e to 7.6, [HCO3-] approximate to 39) and measured J(Ca)(+), and the re lease of osteoclastic beta-glucuronidase and osteoblastic collagen syn thesis. Compared with control, metabolic alkalosis caused a progressiv e decrease in J(Ca)(+), which was correlated inversely with initial me dium pH (pH(i)), Alkalosis caused a decrease in osteoclastic beta-gluc uronidase release, which was correlated inversely with pH(i) and direc tly with J(Ca)(+). Alkalosis also caused an increase in osteoblastic c ollagen synthesis, which was correlated directly with pH(i) and invers ely with J(Ca)(+). There was a strong inverse correlation between the effects alkalosis on osteoclastic beta-glucuronidase release and osteo blastic collagen synthesis. Thus metabolic alkalosis decreases J(Ca)() from bone, at least in part, by decreasing osteoclastic resorption a nd increasing osteoblastic formation. These results suggest that the p rovision of base to neutralize endogenous acid production may improve bone mineral accretion.