The importance of genetic and nutritional factors in responses to vitamin D and its analogs in osteoporotic patients

The effects of vitamin D and its analogs on fractures and bone mass have been clarified by clinical observations for more than 10 years. Reviewing the results of six clinical trials on osteoporotic fractures using activated vitamin D analogs, there appeared to be a negative correlation between basal levels of calcium intake and the incidence of vertebral fractures in the control groups. For example, when daily calcium intake was about 600 mg, there were approximately 800 vertebral fractures per 1000 persons a year in the controls. When daily calcium intake was above 1000 mg, the incidence was less than 400 fractures per 1000 persons a year. The incidence of fractures decreased by about half in the activated vitamin D-treated group compared with the control group, but the most marked preventive effects of activated vitamin D on fractures were obtained in clinical studies, with daily calcium intakes of 400-800 mg. The effects of vitamin D analogs on bone mass were reported in the clinical studies, but the results are not consistent. However, these studies suggest that the effects of both 1,25(OH)(2)D-3 and 1-alpha(OH)D-3 on bone mass were dose dependent, and the doses were low in clinical studies in which good results were not obtained. Significant effects on bone mass were obtained when more than 0.6 mu g of 1,25(OH)(2)D-3, or more than 0.75 mu g of 1-alpha(OH)D-3 was administered, with increase in the urinary calcium level being within the acceptable range. Reported data indicate that both nonactivated vitamin D and activated vitamin D reduce the serum parathyroid hormone level. However, activated vitamin D administration is mole effective, and is able to reduce bone resorption in postmenopausal, osteoporotic patients with a vitamin D-sufficient status. Recent studies concerning the polymorphism of the vitamin D-receptor gene emphasize that sensitivity to active Vitamin D varies between genotypes. In the bb type, sensitivity to active vitamin D is high, and calcium absorption efficiency in the intestine under low calcium conditions increases with increase in the serum 1,25(OH)(2)D level. A significant increase in lumbar bone mineral density was obtained after administration of activated vitamin D to osteoporotic patients of bb type. However, in the genotype with the B factor, sensitivity to active vitamin D was low, and the rate of increase of bone density was low. These data suggest that nutritional and genetic factors are critical when using active vitamin D and its analogs in the treatment of osteoporosis.