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Fluoride Exposure May Accelerate the Osteoporotic Change in Postmenopausal Women: Animal Model of Fluoride-induced Osteoporosis

Mitsuo Kakei, Masayoshi Yoshikawa and Hiroyuki Mishima

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.