Age-related influence of common aromatase gene polymorphisms on bone mass of healthy men.

Androgens and estrogens are critical factors for bone homeostasis; hence, polymorphisms of genes involved in the metabolism and activity of sex steroids are likely candidates to influence bone mass. Therefore, we studied the association of two of those microsatellite polymorphisms, situated in intron 4 of CYP19-aromatase and exon 1 of androgen receptor, with bone mass in a group of 324 healthy men of a wide age range (mean age 49, range 22-75). CYP19 and androgen receptor alleles were typed by capillary electrophoresis after PCR amplification. Bone mass was measured by dual X-ray absorptiometry at the hip and the spine. No association was found between androgen receptor variation and bone mass. However, among the 184 subjects aged more than 45 years, a significant association was found between CYP19 alleles and bone mass at the lumbar spine (P = 0.001) and total hip (P = 0.01). Individuals with long alleles had higher bone mass, even after adjusting for body weight, height, or calcium intake. Mean spine Z scores were -0.1 (95% CI, -0.3 to 0.2), -0.1 (-0.4 to 0.2), and 0.6 (0.3 to 0.9) for individuals with short, intermediate, and long alleles, respectively. Total hip Z scores were 0.4 (0.2 to 0.6), 0.4 (0.2 to 0.6), and 0.8 (0.5 to 1.0), respectively. Longer CYP19 alleles were also associated with higher free estradiol index. These results suggest that common variations in CYP19-aromatase gene may have an important influence on the maintenance of male skeleton after peak bone mass is reached.