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Bisphosphonates and extrarenal acid buffering capacity.

Abstract
Both the intracellular compartment and bone mineral are supposed to play a role in acid-base balance by contributing to the extrarenal acid buffering capacity. Bisphosphonates could affect extrarenal acid buffering capacity by interfering with the formation and/or dissolution of bone mineral. In the present study, rats were pretreated with either 1-hydroxyethylidene-1, 1-bisphosphonate (HEBP, 10 mg/kg.day sc), with prevailing inhibitory action on bone mineral formation, or dichloromethylene bisphosphonate (Cl2MBP, 10 mg p/kg.day sc) with prevailing action on bone resorption, or NaCl injections (controls) for 7 days. In intact rats, blood acid-base variables were influenced by neither HEBP, nor Cl2MBP. Two hours after nephrectomy and before acute acid loading, HEBP-but not Cl2MBP-pretreated rats displayed a significant increase in both blood HCO3- and PCO2. After HCl infusion (2.5 mEq/kg), the relative decrement in blood HCO3- (difference in blood HCO3- before and after acid loading) was transiently more important in the two bisphosphonate pretreated groups than in controls. After a 24 hour fasting period, nephrectomized animals pretreated with Cl2MBP displayed significantly lower blood HCO3- and pH values than controls or HEBP-pretreated rats. These results suggest that bisphosphonates influence extrarenal buffering capacity according to their prevailing inhibitory action on either bone mineral formation and/or dissolution. These compounds could interfere with the release rate of bone proton buffers. However, in the presence of normal renal function, this effect does not disturb the blood acid-base equilibrium.
AuthorsH Freudiger, J P Bonjour
JournalCalcified tissue international (Calcif Tissue Int) Vol. 44 Issue 1 Pg. 3-10 (Jan 1989) ISSN: 0171-967X [Print] United States
PMID2521807 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Buffers
  • Diphosphonates
  • Minerals
  • Clodronic Acid
  • Etidronic Acid
Topics
  • Acid-Base Equilibrium (drug effects)
  • Animals
  • Bone Development (drug effects)
  • Bone Resorption (drug effects)
  • Bone and Bones (metabolism)
  • Buffers
  • Clodronic Acid (pharmacology)
  • Diphosphonates (physiology)
  • Etidronic Acid (pharmacology)
  • Male
  • Minerals (metabolism)
  • Nephrectomy
  • Rats
  • Time Factors

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