Analysis of bone mineral density, fracture rate, markers of bone turnover,and the polymorphisms of vitamin-D-receptor-alleles in an ethnic German subset

Background: It has been reported that the spinal bone density is associated with vitamin-D-receptor (VDR) gene polymorphisms. The results of recent st udies have been contradictory concerning the predictive power for low bone mineral density (BMD). Regional population-specific influences have been fo und to affect the vitamin-D-endocrinologic-system, diminishing the influenc e of VDR polymorphism on BMD and on bone turnover. We have examined the ass ociation 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 heterogenous subset of 164 caucasian subjec ts 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 phospha tase (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 a nd 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% fo r the BB-, 10.8% for the bB- and 0.0% for the bb-genotype. The urinary excr etion rate of free pyridinoline crosslinks was higher for the BB-genotype t han for the bB- or the bb-, however the difference was not significant. No genotype specific variations were seen for bone alkaline phosphatase. Inter pretation: The authors conclude from this study that bone mineral density a t the axial skeleton is associated with the vitamin-D-receptor allele polym orphism and that there is an influence on bone turnover and fracture rate i n 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 osteoporos is for we get prognostic hints concerning the rate of fracture.