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

Objectives: (i) To establish whether the gain in area-adjusted bone mineral content (ABMC) in girls occurs in late puberty. (ii) To examine whether the magnitude of this gain is related to ESR1 polymorphisms.

Design: Cross sectional analysis

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

Participants: 3097 11 yr old participants with DNA samples, DXA measurements and pubertal stage information.

Outcomes: Separate pre-specified analyses in boys and girls of the relationship between ABMC derived from total body DXA scans and Tanner stage, and of the interaction between ABMC, Tanner stage, and ESR1 polymorphisms.

Results: Total body less head (TBLH) 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 TBLH 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 ER-dependent pathway.