Estrogen receptor alpha regulates area-adjusted bone mineral content in late pubertal girls.
BACKGROUND
Whether the action of estrogen in skeletal development depends on estrogen receptor alpha as encoded by the ESR1 gene is unknown.


OBJECTIVE
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.


METHODS
We conducted a cross-sectional analysis.


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


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


RESULTS
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 alpha-dependent pathway.
Tobias
J H
JH
Clinical Science at South Bristol, University of Bristol, Bristol, United Kingdom. Jon.Tobias@bristol.ac.uk
Steer
C D
CD
Vilarino-Güell
C
C
Brown
M A
MA
D015519:Bone Density / Q000235:genetics*; D001846:Bone Development / Q000235:genetics; D001842:Bone and Bones / Q000502:physiology; D002648:Child; D047628:Estrogen Receptor alpha / Q000235:genetics* / Q000378:metabolism*; D004967:Estrogens / Q000378:metabolism; D005260:Female; D006239:Haplotypes; D006801:Humans; D007438:Introns / Q000235:genetics; D015810:Linkage Disequilibrium; D008137:Longitudinal Studies; D011110:Polymorphism, Genetic / Q000502:physiology; D011446:Prospective Studies; D011627:Puberty / Q000235:genetics* / Q000378:metabolism*
D047628:Estrogen Receptor alpha; D004967:Estrogens