Estrogen receptor gene polymorphism, but not estradiol levels, is related to bone density in healthy adolescent boys: a cross-sectional and longitudinal study

J Clin Endocrinol Metab. 1999 Dec;84(12):4597-601. doi: 10.1210/jcem.84.12.6238.


The purpose of the present study was to investigate the influence of estrogen receptor alpha gene polymorphism and estradiol on height and bone density during and after puberty in males. Using the restriction enzymes XbaI and PvuII, the allelic variants XX, Xx, xx, PP, Pp, and pp were identified in 90 Caucasian boys 16.9+/-0.3 yr of age (mean +/- SD). Bone mineral density (BMD; g/cm2) of the total body, head, femoral neck, and lumbar spine was measured using dual-energy x-ray absorptiometry. Volumetric BMD (vBMD; mg/cm3) was estimated for the spine. The XbaI or PvuII genotypes were not related to the levels of estradiol, and the levels of estradiol were not related to BMD (P > 0.05). The xx allelic variant was associated with a higher spine vBMD than the Xx allelic variant (361 vs. 340 mg/cm3, P = 0.04). In a multivariate analysis including pubertal development, physical activity, and body weight, the XbaI genotype independently predicted total body BMD, head BMD, and spine vBMD (P < 0.05). The PvuII genotype independently predicted spine vBMD (pp > PP, P = 0.01). The 20 boys with the PP allelic variant were found to have a greater body height than the other 70 boys (182 cm vs. 179 cm, P = 0.03). At a 2-yr follow-up the XbaI genotype was still independently related to total body BMD, head BMD, and spine vBMD. In conclusion, estrogen receptor gene polymorphism is related to bone density and height during late puberty and at attainment of peak bone density in young men.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Absorptiometry, Photon
  • Adolescent
  • Bone Density*
  • Cross-Sectional Studies
  • Deoxyribonucleases, Type II Site-Specific
  • Estradiol / blood*
  • Genotype
  • Humans
  • Longitudinal Studies
  • Male
  • Polymorphism, Restriction Fragment Length*
  • Puberty
  • Receptors, Estrogen / genetics*


  • Receptors, Estrogen
  • Estradiol
  • endodeoxyribonuclease XBAI
  • CAGCTG-specific type II deoxyribonucleases
  • Deoxyribonucleases, Type II Site-Specific