BMJ 1995;310:1357-1360 (27 May)

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Influence of vitamin D receptor genotype on bone mineral density in postmenopausal women: a twin study in Britain

T D Spector, consultant rheumatologist,a R W Keen, research fellow of Arthritis and Rheumatism Council,a N K Arden, Wellcome research fellow,a N A Morrison, senior scientist,c P J Major, research assistant,a T V Nguyen, statistician,c P J Kelly, senior lecturer,c J R Baker, research nurse,a P N Sambrook, associate professor,c J S Lanchbury, senior lecturer,b J A Eisman, professor c

a Rheumatology Department, United Medical and Dental School, St Thomas's Hospital, London SE1 7EH, b Molecular Immunogenetics Units, United Medical and Dental School, c Bone and Mineral Research Division, Garvan Institute of Medical Research, Sydney, Australia

Correspondence to: Dr Spector.

Abstract

Objectives: To investigate the possible association between vitamin D receptor genotype and bone mineral density in a large group of postmenopausal twins.
Design: Cross sectional twin study.
Setting: Twin population based in Britain.
Subjects: 95 dizygotic (non-identical) pairs of twins and 87 monozygotic (identical) pairs of twins aged 50-69 years, postmenopausal, and free of diseases affecting bone, recruited from a national register of twins and with a media campaign.
Main outcome measures: Bone mineral density measured at the hip, lumbar spine, forearm, and for the whole body by dual energy x ray absorptiometry in relation to differences in the vitamin D receptor genotype.
Results: At all sites the values of bone density among dizygotic twins were more similar in those of the same vitamin D receptor genotype than in those of differing genotype, and the values in the former were closer to the correlations seen in monozygotic twins. Women with the genotype that made them at risk of osteoporotic fracture had an adjusted bone mineral density that was significantly lower by SD 0.5 to 0.6 at the hip, lumbar spine, and for the whole body. The results could not be explained by differences in age, weight, years since menopause, or use of hormone replacement therapy.
Conclusions: The findings that in postmenopausal women in Britain bone density--particularly at the hip and spine--is genetically linked and specifically associated with the vitamin D receptor genotypes should lead to novel approaches to the prevention and treatment of osteoporosis.

Key messages

  • Key messages

  • Vitamin D has an important role in the metabolism of calcium and bone, mediated through its receptor

  • Common variants of the vitamin D receptor gene are responsible for 7-10% of the difference in bone density between women after the menopause

  • This genetic marker is important because of its potential role in identifying individual women at increased risk of fracture before menopause and in selecting optimal treatment


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