Epidemiological studies during 1963-1997 were conducted in 45,725 children exposed to high intake of endemic fluoride in the drinking water since their birth. Children with adequate (dietary calcium > 800 mg/d) and inadequate (dietary calcium < 300 mg/d) calcium nutrition and with comparable intakes of fluoride (mean 9.5 +/- 1.9 mg/d) were compared. The toxic-effects of fluoride were severe and more complex and the incidence of metabolic bone disease (rickets, osteoporosis. PTH bone disease) and bony leg deformities (genu valgum, genu varum, bowing, rotational and wind-swept) was greater (> 90%) in children with calcium deficiency as compared to < 25% in children with adequate calcium who largely had osteosclerotic form of skeletal fluorosis with minimal secondary hyperparathyroidism. The syndrome of skeletal fluorosis and associated metabolic bone disease and deformity is a unique clinical entity classified as a variant of osteosclerotic form of skeletal fluorosis. This syndrome chiefly results from the biological impact of excess fluoride, low calcium, high PTH and 1,25 (OH)2D3 separately and through their interactions on bone structure and metabolism as studied by radiology, bone scanning, bone histomorphometry and relevant metabolic and endocrine laboratory investigations. Metabolically active and vascular bones of children accumulate fluoride at faster and greater rate than adults (at the sites of active growth). In calcium deficient children the toxic effects of fluoride manifest even at marginally high (> 2.5 mg/d) exposures to fluoride. Fluoride toxicity also exaggerates the metabolic effects of calcium deficiency on bone. The findings strongly suggest that children with calcium deficiency rickets reported in the literature should be re-investigated for possible fluoride interactions. Deep bore drinking water supply with fluoride < 0.5 ppm and improvement of calcium nutrition provide 100% protection against the toxic effects of fluoride and are recommended as the cost effective and practical public health measures for the prevention and control of endemic fluorosis.