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[Bone density and bone metabolism regulated by vitamin D receptor allele polymorphism in a German study sample].

BACKGROUND
It has been reported that the spinal bone density is associated with vitamin-D-receptor (VDR) gene polymorphisms. The results of recent studies have been contradictory concerning the predictive power for low bone mineral density (BMD). Regional population-specific influences have been found to affect the vitamin-D-endocrinologic-system, diminishing the influence of VDR polymorphism on BMD and on bone turnover. We have examined the association of bone density, fracture predictivity and biochemical markers of bone turnover with VDR polymorphism in a German population.


METHODS
Blood and urine were collected from a heterogeneous subset of 164 caucasian subjects with ethnic German background. Polymerase chain reaction and subsequent digestion with Bsm I were used to examine variations of VDR genotypes. The morning following initial specimen collections, both urinary excretion rate of pyridinoline crosslinks (Pyr) and serum levels of bone alkaline phosphatase (BAP) were determined. For determination of the bone mineral density, the well-established method of dual X-ray absorptiometry was used.


FINDINGS
The VDR BB-genotype was associated with low bone mineral density for age-matched subjects (90.1 +/- 15.5%) versus the bb-genotype (100.8 +/- 10.8%) at the lumbar spine and at the Ward's triangle (91.8 +/- 17.9% versus 101.9 +/- 12.1%). 34.2% of BB-genotype subjects, 14.2% of bB-genotype subjects and 12.6% of bb-genotype subjects had Z-score related bone mineral density < 85%. The fracture rate at typical osteoporotic fracture sites was 23.6% for the BB-, 10.8% for the bB- and 0.0% for the bb-genotype. The urinary excretion rate of free pyridinoline crosslinks was higher for the BB-genotype than for the bB- or the bb-, however the difference was not significant. No genotype specific variations were seen for bone alkaline phosphatase.


INTERPRETATION
The authors conclude from this study that bone mineral density at the axial skeleton is associated with the vitamin-D-receptor allele polymorphism and that there is an influence on bone turnover and fracture rate in a German subset.


CLINICAL RELEVANCE
The analysis of the VDR-genotype can be considered as a new piece in the puzzle of the diagnostic of osteoporosis for we get prognostic hints concerning the rate of fracture.