Evidence of Sexual Dimorphism in Relationships Between Estrogen Receptor Polymorphisms and Bone Mass: the Hertfordshire Study

ELAINE DENNISON, HOLLY SYDDALL, CAROLINE FALL, MARIA LUISA BRANDI, CYRUS COOPER, and the Hertfordshire Cohort Study Group

ABSTRACT.

Objective. To examine the relationship between estrogen receptor (ER) a and ß gene polymorphisms and bone mass.

Methods. Bone mineral density (BMD) was measured at the lumbar spine and proximal femur twice, 4 years apart, in a cohort of 147 men and 125 women aged 61-73 years. Genomic DNA was extracted from whole blood samples, and genotyping for the ER (PvuII, XbaI, and AluI) was undertaken.

Results. There were no significant associations between either the XbaI or PvuII polymorphisms and bone mass, or bone loss in the cohort as a whole. However, men homozygous for the aa ß receptor polymorphism had higher BMD at the lumbar spine (p = 0.05), femoral neck (p = 0.01), and total femur (p = 0.01). Women homozygous for aa had lower femoral neck and total femoral BMD than women of the AA or Aa genotypes (p = 0.01 and p = 0.02). Gender*ERß interaction terms were statistically significant (p = 0.02 for lumbar spine BMD, p = 0.0004 for femoral neck BMD, and p = 0.0003 for total femoral BMD, each test with 2 degrees of freedom unadjusted). Adjustment for sex hormone concentration and lifestyle factors made little difference to our results.

Conclusion. We found relationships between the ERß gene and the determination of bone mass among men and women in their seventh decade. (J Rheumatol 2005;32:2400-4)

Key Indexing Terms:

ESTROGEN RECEPTOR
INTERACTION
BONE

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From the MRC Epidemiology Resource Centre, University of Southampton, Southampton General Hospital, Southampton, England; and the Department of Internal Medicine, University of Florence, Florence, Italy.

Supported by a project grant from the Arthritis Research Campaign (EMD/CC), and grants from the fondazione Ente Cassa di Risparmio di Firenze and MIUR 40% project (MLB). Dr. E. Dennison received a Wellcome Training Fellowship in Clinical Epidemiology.

E.M. Dennison, PhD, MRCP, Consultant Rheumatologist; H.E. Syddall, MSc, Medical Statistician; C.H.D. Fall, PhD, Reader in Paediatric Epidemiology, MRC Epidemiology Resource Centre, University of Southampton; M.L. Brandi, PhD, Professor of Endocrinology, Department of Internal Medicine, University of Florence; C. Cooper, DM, FRCP, Professor of Rheumatology, MRC Epidemiology Resource Centre, University of Southampton; Hertfordshire Cohort Study Group: A. Aihie Sayer, PhD; D.I.W. Phillips, PhD; I.N.M. Day, PhD; D.J.P. Barker, PhD; V.A. Cox.

Address reprint requests to Dr. E. Dennison, MRC Epidemiology Resource Centre, Southampton General Hospital, Southampton SO16 6YD, England. E-mail: emd@mrc.soton.ac.uk

Accepted for publication July 18, 2005.

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