Journal
CURRENT OPINION IN NEPHROLOGY AND HYPERTENSION
Volume 13, Issue 4, Pages 423-436Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/01.mnh.0000133975.32559.6b
Keywords
acidosis; bone resorption; prostaglandins; calcium; proton
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Funding
- NIAMS NIH HHS [AR-46289] Funding Source: Medline
- NIDDK NIH HHS [DK-56788] Funding Source: Medline
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Purpose of review This review presents our current understanding of the way metabolic acidosis induces calcium efflux from bone, and in the process, buffers additional systemic hydrogen ions associated with acidosis. Recent findings Acid-induced changes in bone mineral are consistent with a role for bone as a proton buffer. In response to metabolic acidosis in an in-vitro bone organ culture system, we observed a fall in mineral sodium, potassium, carbonate and phosphate, which each buffer protons and in vivo should increase systemic pH towards the physiologic normal. Initially, metabolic acidosis stimulates physicochemical mineral dissolution and subsequently cell-mediated bone resorption. Acidosis suppresses the activity of bone-resorbing cells, osteoblasts, decreasing gene expression of specific matrix proteins and alkaline phosphatase activity. There is concomitant acid stimulation of prostaglandin production by osteoblasts, which acting in a paracrine manner increases synthesis of the osteoblastic receptor activator of nuclear factor kappa B ligand (RANKL). The acid induction of RANKL then stimulates osteoclastic activity and recruitment of new osteoclasts to promote bone resorption and buffering of the proton load. Both the regulation of RANKL and acid-induced calcium efflux from bone are mediated by prostaglandins. Summary Metabolic acidosis, which occurs during renal failure, renal insufficiency or renal tubular acidosis, results in decreased systemic pH and is associated with an increase in urine calcium excretion. The apparent protective function of bone to help maintain systemic pH, which has a clear survival advantage for mammals, will come partly at the expense of its mineral stores.
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