The Mechanism of Fluoride-Induced Hypocalcaemia

Abstract

<jats:p> 1 Fluoride intoxication leads to sudden cardiac death which has been assumed to result from the accompanying severe hypocalcaemia. The aim of this study has been to investigate the suggestion that fluorapatite formation rather than CaF<jats:sub>2</jats:sub> precipitation is responsible for this low calcium. </jats:p><jats:p> 2 Measurements of free Ca<jats:sup>2+</jats:sup> and F<jats:sup>-</jats:sup> ion concentrations in HEPES buffered solutions containing F-, Ca<jats:sup>2+</jats:sup>, and phosphate ions at different concentrations in the absence and presence of hydroxyapatite showed that the presence of hydroxyapatite enhanced the decrease of Ca<jats:sup>2+</jats:sup> and F- concentration. </jats:p><jats:p> 3 The ratio of Ca<jats:sup>2+</jats:sup>:F<jats:sup>-</jats:sup> clearance was 5:1 which is consistent with formation of fluorapatite. These results support the hypothesis that hydroxyapatite acts as a nucleation catalyst for fluorapatite formation and this process is responsible for the hypocalcaemia induced by fluoride intoxication. </jats:p><jats:p> 4 The proposed mechanism explains also the metabolic acidosis which is frequently seen in cases of fluoride intoxication. </jats:p>

Modulation of Fluoride Toxicity in Rats by Calcium Carbonate and by Withdrawal of Fluoride Exposure

“…A poor gastrointestinal absorption of calcium that resulted from formation of a poorly soluble calcium fluoride or fluorapatite (Boink et al 1994) and a promotion by fluoride of uptake of calcium by bone (Farley et al 1983), accounted for hypocalcaemia in these animals. Inadequate food intake can also be a contributing factor for hypocalcaemia.…”

Recurrent life-threatening ventricular dysrhythmias associated with acute hydrofluoric acid ingestion: Observations in one case and implications for mechanism of toxicity

“…Discussions of the management of fluoride toxicity have emphasized the importance of hypocalcemia and its prompt treatment to avoid cardiac complications (1,2,11,(17)(18)(19)(20)(21)(22). Hyperkalemia, which may be delayed in onset, has also been proposed as an etiology of fluoride-associated ventricular dysrhythmias (4,18,(23)(24)(25)(26)(27).…”

Time‐dependent Changes of Blood Parameters and Fluoride Kinetics in Rats after Acute Exposure to Subtoxic Hydrofluoric Acid

“…The kidney is the main target of F toxicity. We propose that the elimination of HFA is decreased by the deterioration of renal function; however, it has also been proposed that the serum concentration of F is decreased by the short half-life of F 21) , the formation of CaF 2 14) and fluorapatite 18) . Therefore AUC and the serum concentration of F in the 300-min group did not increase considerably.…”

“…Simpson et al postulated that formation of fluorapatite rather than formation of CaF 2 is responsible for the decrease of the plasma calcium concentration 17) . As a mechanism of fluorapatite formation caused by F, two in vitro studies showed that hydroxyapatite acts as a nucleation catalyst for fluorapatite formation and that collagenous matrix induced a similar fluorapatite formation 18,19) . Because rapid formation of fluorapatite occurred after the addition of a trace amount of F irrespective of the presence of hydroxyapatite in the circulation 18) , this process would have been responsible for the hypocalcemia induced by the low serum concentration of F. The amount of Ca × P product decreased in the 5-, 10-, and 30-min groups and the P level increased in the 120-and 300-min groups in the case of the 9.6 mg/kg dose.…”

“…As a mechanism of metabolic acidosis caused by F, it was reported that the HCO 3 -level and BE decreased owing to renal tubular acidosis 60 min after HFA administration (9.6 mg/kg) 9) . It was also postulated that formation of fluorapatite requires dissociation of HPO 4 2-, which releases protons causing metabolic acidosis 18) . These combined effects would delay the recovery of BE and HCO 3 -levels.…”