Calcium deficiency in fluoride-treated osteoporotic patients despite calcium supplementation.

Abstract

To test the hypothesis that the osteogenic response to fluoride can increase the skeletal requirement for calcium, resulting in a general state of calcium deficiency and secondary hyperparathyroidism, we assessed calcium deficiency, spinal bone density, by quantitative computed tomography, and serum PTH in three groups of osteoporotic subjects. Two of the three groups had been treated with fluoride and calcium (at least 1500 mg/day) for 32 +/- 19 months. Group 1 consisted of 16 fluoride-treated subjects who had shown rapid increases in spinal bone density (+ 3.8 +/- 2.6 mg/cm2 month), group II consisted of 10 fluoride-treated subjects who had shown decreases or only slow increases in spinal bone density (-0.05 +/- 0.6 mg/cm3 month), and group III consisted of 10 age-matched untreated osteoporotic controls. Calcium deficiency was assessed by measurement of calcium retention after calcium infusion. The results of our studies showed that 1) 94% of the subjects in Group I were calcium deficient compared with only 30% in groups II and III (P < 0.01 for each); 2) the subjects in group I retained more calcium (79%) than the subjects in group II (60%, P < 0.001) or the subjects in group III (64%, P < 0.005); 3) calcium retention was proportional to serum PTH (r = 0.37, n = 36, P < 0.03); and 4) calcium retention was proportional to the (previous) fluoride-dependent increase in quantitative computed tomography spinal bone density (in groups I and II, r = 0.48, n = 26, P < 0.02). To test the hypothesis that the calcium deficiency and the secondary hyperparathyroidism that were associated with the positive response to fluoride would respond to concomitant calcitriol treatment, a subgroup of 7 calcium-deficient subjects were selected from group I and treated with calcitriol (plus fluoride and calcium) for an average of 7 months. The calcitriol therapy reduced the calcium deficit in all 7 subjects, decreasing calcium retention from 80% to 62% (P < 0.02), and decreasing PTH from 50 to 28 pg/mL (P < 0.02). Together, these data indicate that fluoride-treated osteoporotic subjects may develop calcium deficiency in proportion to the effect of fluoride to increase bone formation, and this calcium deficit is responsive to calcitriol therapy.

Fluoride: A toxic or therapeutic agent in the treatment of osteoporosis?

“…Controlled clinical studies are still lacking to elucidate whether the combinations are more efficient than the individual drugs in reducing osteoporotic fractures. Supplements with high-dosed calcium and vitamin D are recommended for patients treated with several of the combinations discussed [50].…”

“…Extensive replacement of hydroxyl groups with fluoride is thought to lead to skeletal fluorosis, which has been reported in doses as low as 20 mg daily after many years of exposure, when the bone deposits exceed a threshold of about 0.6% of bone ash [23,25,55]. Such exposure for fluoride can also reduce the bioavailability of calcium [50]. Therefore, it is possible that the reported decreased mechanical qualities of, for example, hip bone can be mediated by a certain degree of secondary hyperparathyroidism induced by calcium deprivation.…”

“…Such observations have precipitated the recommendations that treatment with fluorides should make use of low or moderate doses, in the range 15À25 mg F daily [32,35,36], and supplements of calcium and vitamin D should always be added to the treatment [50]. Such supplementation is especially important when using combined therapy of fluoride and bisphosphonates.…”

Effects of fluorosis on QT dispersion, heart rate variability and echocardiographic parameters in children

“…In a study, they detected sinusoidal bradycardia, prolongation of PR in sheep that rendering to high fluoride (25). Same findings were observed in residents of Japanese village (27).…”

“…Fluoride strongly binds to calcium. It results in hypocalcemia, and hyperkalemia (25,26). Calcium levels were significantly lower in both study groups than control group.…”