Mutational and polymorphic analysis of the estradiol receptor-alpha gene in men with symptomatic vertebral fractures.

In view of the importance of estrogens in the maintenance of the skeleton in men, we have carried out mutational analysis of all the exons of the estrogen-receptor-alpha (ER-alpha) gene in 64 men (36 patients with symptomatic vertebral crush fractures and 28 control subjects). Initial screening of the ER-alpha gene, carried out by single-strand conformation polymorphism analysis followed by sequencing, showed conservative mutations in exon 4 which resulted in a single base substitutions producing GGG-->GGC transition in codon 274. We also carried out polymorphic analysis of the ER-alpha gene at the PvuII restriction site in 82 men with a range of bone density measurements (53 with symptomatic vertebral fractures and 29 controls). The frequencies of PP, Pp, and pp genotypes were 20.7%, 48.8%, and 30.5%, respectively. The distribution of the alleles was similar in the patients with symptomatic vertebral crush fractures and male control subjects. There was no association between ER-alpha genotypes and bone mineral density or arthropometric parameters. This relatively small study suggests that mutations in the ER-alpha gene are unlikely to be a common cause of osteoporosis in men with vertebral fractures. Furthermore, polymorphic variation of the ER-alpha gene appears to have little effect on the pathogenesis of osteoporosis in men.