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Estrogen Receptor Regulates Area-Adjusted Bone Mineral Content in Late Pubertal Girls

J. H. Tobias, C. D. Steer, C. Vilario-Güell and M. A. Brown

Clinical Science at South Bristol (J.H.T.), Community Medicine (C.D.S.), University of Bristol, Bristol BS2 8HW, United Kingdom; Botnar Research Centre (C.V.-G., M.A.B.), University of Oxford, Oxford BS2 8HW, United Kingdom; and Centre for Immunology and Cancer Research (M.A.B.), University of Queensland, Queensland 4102, Australia

Address all correspondence and requests for reprints to: Dr. J. Tobias, Rheumatology Unit, Bristol Royal Infirmary, Bristol BS2 8HW, United Kingdom. E-mail: Jon.Tobias{at}bristol.ac.uk.

Context: Whether the action of estrogen in skeletal development depends on estrogen receptor as encoded by the ESR1 gene is unknown.

Objectives: The aim of this study was to establish whether the gain in area-adjusted bone mineral content (ABMC) in girls occurs in late puberty and to examine whether the magnitude of this gain is related to ESR1 polymorphisms.

Design: We conducted a cross-sectional analysis.

Setting: The study involved the Avon Longitudinal Study of Parents and Children (ALSPAC), a population-based prospective study.

Participants: Participants included 3097 11-yr-olds with DNA samples, dual x-ray absorptiometry measurements, and pubertal stage information.

Outcomes: Outcome measures included separate prespecified analyses in boys and girls of the relationship between ABMC derived from total body dual x-ray absorptiometry scans and Tanner stage and of the interaction between ABMC, Tanner stage, and ESR1 polymorphisms.

Results: Total body less head and spinal ABMC were higher in girls in Tanner stages 4 and 5, compared with those in Tanner stages 1, 2, and 3. In contrast, height increased throughout puberty. No differences were observed in ABMC according to Tanner stage in boys. For rs2234693 (PvuII) and rs9340799 (XbaI) polymorphisms, differences in spinal ABMC in late puberty were 2-fold greater in girls who were homozygous for the C and G alleles, respectively (P = 0.001). For rs7757956, the difference in total body less head ABMC in late puberty was 50% less in individuals homozygous or heterozygous for the A allele (P = 0.006).

Conclusions: Gains in ABMC in late pubertal girls are strongly associated with ESR1 polymorphisms, suggesting that estrogen contributes to this process via an estrogen receptor -dependent pathway.

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				J. H. Tobias, C. D. Steer, C. Vilarino-Guell, and M. A. Brown Effect of an Estrogen Receptor-{alpha} Intron 4 Polymorphism on Fat Mass in 11-Year-Old Children J. Clin. Endocrinol. Metab., June 1, 2007; 92(6): 2286 - 2291. [Abstract] [Full Text] [PDF]