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Estrogen Receptor Genotypes and Their Association with the 10-Year Changes in Bone Mineral Density and Osteocalcin Concentrations

Departments of Epidemiology (M.S., M.L.J.) and Biostatistics (W.L.), School of Public Health, University of Michigan, Ann Arbor, Michigan 48104; and Department of Pediatrics (M.W.), University of Iowa, Iowa City, Iowa 52242

Address all correspondence and requests for reprints to: MaryFran Sowers, Ph.D., 339 East Liberty, Suite 310, Ann Arbor, Michigan 48104. E-mail: mfsowers{at}umich.edu.

We conducted a 10-yr prospective study of peak bone mass and its change in 604 women, aged 24–44 yr at study initiation, and related changes in bone mineral density (BMD) and osteocalcin (OCN) concentrations to estrogen receptor (ER) gene polymorphisms in 442 of these women.

We examined the association of ER PvuII and XbaI polymorphisms with the 10-yr change in lumbar spine (LS) and femoral neck (FN) BMD, measured by densitometry, as well as serum OCN levels, after accounting for weight and menstrual status change. The women were members of the Michigan Bone Health Study, a population-based longitudinal study of BMD.

There was a linear loss of LS BMD and curvilinear loss of FN BMD from peak bone mass over a 10-yr period. Women homozygous for the ER gene variant without an XbaI restriction site (XbaI -/- genotype) had higher FN BMD and less change in LS over time. Women homozygous for the ER gene variant without a PvuII restriction site (PvuII -/- genotype) had less LS BMD change over time as well as higher FN BMD. However, this higher FN BMD was dependent upon the rate of bone turnover as estimated from serum OCN change over time.

The ER genotype associations were statistically significant in explaining the rate of perimenopausal bone loss and its turnover; however, BMI or becoming postmenopausal contributed more to the magnitude of the difference in bone change.

This work was supported by Grants AR R01-40888 [to M.S., Principal Investigator (PI)], AR P60-20557 (to M.S., PI), and NIAMS R55-43507 (to M.W., PI).

Abbreviations: BMD, Bone mineral density; BMI, body mass index; ER, estrogen receptor; FN, femoral neck; HRT, hormone replacement therapy; LS, lumbar spine; OCN, osteocalcin.

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