Abstract
The effects of 1, 24(R)-dihydroxyvitamin D3(1, 24(R)(OH)2D3), 1, 25-dihydroxyvitamin D3(1, 25(OH)2D3) and 1α-hydroxyvitamin D3(1α(OH)D3) on the development of osteoporosis in ovariectomized rats were investigated biochemically and histomorphologically. Vitamin D3 analogs dissoloved in corn oil were given orally to the rats for 6 months after the ovariectomy. The sham-operated control animals received the vehicle alone. Ovariectomy was followed by the development of osteoporosis after 6 months of observation. This was characterized by a reduction in ash content of the tibia and histjologically by a disappearance of the trabecular bone in tibial metaphysis. Biochemical studies showed significant decreases in serum calcium and 1, 25(OH)2D concentrations, and significant increases in serum immunoreactive parathyroid hormone (iPTH) level in ovariectomized rats. These findings suggest that ovariectomy partially impairs intestinal absorption of calcium, increases bone resorption, and results in a negative calcium balance, which may contribute to the development of osteoporosis in rats. The administration of 1, 24(R)(OH)2D3, 1, 25(OH)2D3 and 1α(OH)D3 increased dose-dependently serum and urinary calcium, but decreased serum iPTH levels to the control level and prevented the development of osteoporosis histologically. These results support the view that active vitamin D3 analogs may be valable tools for the treatment of osteoporosis.
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