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Bone Mineral Mass and Calcium and Phosphate Metabolism in Young Men: Relationships with Vitamin D Receptor Allelic Polymorphisms¹

Division of Bone Diseases, World Health Organization Collaborating Center for Osteoporosis and Bone Diseases, Department of Internal Medicine, University Hospital, 1211 Geneva 14, Switzerland

Address all correspondence and requests for reprints to: René Rizzoli, M.D., Division of Bone Diseases, Department of Internal Medicine, University Hospital, 1211 Geneva 14, Switzerland. E-mail: rizzoli{at}cmu.unige.ch

The genetic bases of peak bone mass determinants are still poorly understood, particularly in males. We investigated the relationship between vitamin D receptor (VDR) 3'- and 5'-gene polymorphisms (as determined by the restriction enzymes BsmI and FokI) and bone mineral mass, and calcium and inorganic phosphate (Pi) metabolism in an homogeneous cohort of young healthy men. In 104 healthy subjects, aged 24.3 ± 3.1 yr (mean ± SD; range, 20.7–38.7), standardized bone mineral density (BMD; z-scores) at the levels of lumbar spine and femoral trochanter, i.e. bone mineral content adjusted for age, body size, and bone area, significantly differed between VDR 3'-end alleles (BsmI), whereas crude areal BMD or bone mineral content did not. Among BsmI homozygotes BB, BMD (z-scores) were significantly lower only in subjects also carrying the f allele at the VDR-5' polymorphic site (FokI). Serum PTH levels were significantly higher in the BB genotype at baseline and remained so under either a low or a high calcium-phosphorus diet. Moreover, on the low calcium-phosphorus diet, BB subjects had significantly decreased tubular Pi reabsorptive capacity and plasma Pi levels. Our results underline the importance of identifying multiple single base mutation polymorphisms within candidate genes of bone mineral mass and suggest a role for environmental/dietary factor interactions with VDR gene polymorphisms in peak bone mineral mass in men.

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