Bushinsky D A
Department of Medicine, University of Rochester School of Medicine, New York 14642, USA.
Am J Physiol. 1996 Jul;271(1 Pt 2):F216-22. doi: 10.1152/ajprenal.1996.271.1.F216.
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 (JCa+) from bone and bone cell function, we cultured neonatal mouse calvariae for 48 h in either control medium (pH approximately equal to 7.4, [HCO3-] approximately equal to 24), medium simulating mild alkalosis (pH approximately equal to 7.5, [HCO3-] approximately equal to 31), or severe alkalosis (pH approximately equal to 7.6, [HCO3-] approximately equal to 39) and measured JCa+ and the release of osteoclastic beta-glucuronidase and osteoblastic collagen synthesis. Compared with control, metabolic alkalosis caused a progressive decrease in JCa+, which was correlated inversely with initial medium pH (pHi). Alkalosis caused a decrease in osteoclastic beta-glucuronidase release, which was correlated inversely with pHi and directly with JCa+. Alkalosis also caused an increase in osteoblastic collagen synthesis, which was correlated directly with pHi and inversely with JCa+. There was a strong inverse correlation between the effects alkalosis on osteoclastic beta-glucuronidase release and osteoblastic collagen synthesis. Thus metabolic alkalosis decreases JCa+ 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.
体内和体外证据表明，代谢性酸中毒可能在代谢终产物完全排泄之前发生，它会增加尿钙排泄。额外的尿钙几乎肯定来自骨矿物质。通过提供碱来中和每日的酸负荷，可减少钙排泄，这表明碱可能会影响骨钙的增加。为了确定代谢性碱中毒是否会改变骨的净钙流出（JCa+）和骨细胞功能，我们将新生小鼠颅骨在对照培养基（pH约等于7.4，[HCO3-]约等于24）、模拟轻度碱中毒的培养基（pH约等于7.5，[HCO3-]约等于31）或重度碱中毒的培养基（pH约等于7.6，[HCO3-]约等于39）中培养48小时，并测量JCa+以及破骨细胞β-葡萄糖醛酸酶的释放和成骨细胞胶原蛋白的合成。与对照相比，代谢性碱中毒导致JCa+逐渐降低，这与初始培养基pH（pHi）呈负相关。碱中毒导致破骨细胞β-葡萄糖醛酸酶释放减少，这与pHi呈负相关，与JCa+呈正相关。碱中毒还导致成骨细胞胶原蛋白合成增加，这与pHi呈正相关，与JCa+呈负相关。碱中毒对破骨细胞β-葡萄糖醛酸酶释放和成骨细胞胶原蛋白合成的影响之间存在强烈的负相关。因此，代谢性碱中毒至少部分地通过减少破骨细胞吸收和增加成骨细胞形成来降低骨的JCa+。这些结果表明，提供碱来中和内源性酸产生可能会改善骨矿物质的增加。
