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

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alkalosis / metabolism*
  • Alkalosis / pathology*
  • Animals
  • Bone and Bones / metabolism*
  • Bone and Bones / pathology
  • Calcium / metabolism*
  • Collagen / biosynthesis
  • Glucuronidase / metabolism
  • Mice
  • Organ Culture Techniques
  • Osteoblasts / pathology*
  • Osteoclasts / metabolism
  • Osteoclasts / pathology*
  • Skull


  • Collagen
  • Glucuronidase
  • Calcium