LACK OF A HIGH PREVALENCE OF THE BB-VITAMIN-D-RECEPTOR GENOTYPE IN SEVERELY OSTEOPOROTIC WOMEN

Studies of twins strongly suggest that more than 50% of the peak spina l bone density is determined by genetics. It was reported recently tha t this genetic effect is primarily determined by vitamin D receptor (V DR) alleles; specifically, a VDR genotype termed BE has been highly as sociated with low peak bone density. Homozygotes for the second VDR al lele, bb, are associated w;ith high peak bone density. If peak bone de nsity is an important determinant of osteoporosis and if the VDR genot ype is an important determinant of peak bone density, then patients wi th severe osteoporosis should have a high prevalence of the BE VDR gen otype compared with that of control subjects. To test this hypothesis, we used Southern blot analysis to determine the VDR genotype of 41 Ca ucasian patients (72 +/- 14.yr) with severe osteoporosis (27 women wit h spinal bone densities below 50 mg/cm(3) as determined by quantitativ e computed tomography; 14 women with spinal bone densities below 0.75 g/cm(2) as determined by dual energy x-ray absorptiometry) and 23 Cauc asian control subjects (68 +/- 7 yr) without osteoporosis (quantitativ e computed tomography values at or above the fracture threshold of 100 mg/cm(3)). Only 6 of the 41 individuals in the group with severe oste oporosis had the BB genotype, whereas 16 had the bb genotype. In the c ontrol group comprising 23 individuals, 7 had the BB genotype and only 6 had the bb genotype. We conclude that the BB VDR genotype is not a good predictor of risk for developing severe osteoporosis in our popul ation.