Abstract
Carbonic anhydrase is a key enzyme for initiating the crystal nucleation, seen as “the central dark line” in the crystal structure in calcified hard tissues such as tooth enamel, dentin and bone. Both estrogen deficiency and fluoride exposure adversely affected the synthesis of this enzyme in the calcifying hard tissues. This led to the notion that fluoride exposure might increase the risk of developing osteoporosis in postmenopausal women. Using ovariectomized rats, which represent an estrogen (Es)-deficient state, as an animal model of postmenopausal women, we examined the causal relationship between fluoride (F) exposure and risk of developing osteoporosis. Two groups of rats, an Es-deficient group and a non-Es-deficient group, were administered free drinking water containing F ions (1.0 mg/L). Two other groups, an Es-deficient group and a control-group, were administered tap water. Soft X-ray radiography demonstrated a significant increase of radiolucent areas in the calvaria of the combined Esdeficient plus F group compared to that in the other experimental groups. Electron microscopy revealed an increase of amorphous minerals in the radiolucent areas. Light microscopy demonstrated that combined effects evidently of Es-deficiency and administration of F caused deterioration of the rat tibia with a coarse pattern of trabecular architecture, suggesting that a decline in bone formation might be the primary cause of osteoporosis. Consequently, F exposure might accelerate osteoporotic changes in postmenopausal women even at a low dose.
Highlights
Osteoporosis is a major health problem among aging people and occurs predominantly in postmenopausal women
Concerning the crystals in the calvaria of the combined group, at low magnification, electron microscopy demonstrated that the radiolucent areas of the calvaria were filled with fine needle-shaped minerals with less electron density (Figure 2c), whereas the radiopaque areas contained relatively thick and electron-dense minerals similar to those of the control (Figures 2a and 2b)
A b c animals (Figures 3a and 3b). Most of these needle-shaped minerals in the radiolucent areas had ill-defined features and lacked the central dark lines (CDLs) or lattice fringes commonly observed in sound crystals, indicating that the radiolucent areas were filled with amorphous minerals (Figure 3c)
Summary
Osteoporosis is a major health problem among aging people and occurs predominantly in postmenopausal women. Various risk factors have been identified that are associated with the development of osteoporosis [1,2,3,4,5,6] Among those factors, estrogen (Es) deficiency is well known to increase the risk of postmenopausal osteoporosis. In the case of fluoride (F) exposure, the detrimental effect of F ions on the crystal nucleation process far exceeded that of Cd ions [14,15]. This led to the assumption that F schemes for caries prevention might leave postmenopausal women exposed to a high risk of developing osteoporosis without any beneficial effects
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