Baltzer A W, Reinecke J, Wehling P, Granrath M, Schulitz K P
Orthopädische Universitätsklinik der Heinrich-Heine-Universität, Düsseldorf.
Z Orthop Ihre Grenzgeb. 1999 May-Jun;137(3):273-9. doi: 10.1055/s-2008-1037406.
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.
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.
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.
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.
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.
据报道，脊柱骨密度与维生素D受体（VDR）基因多态性相关。近期研究结果在预测低骨矿物质密度（BMD）的能力方面存在矛盾。已发现特定区域人群的影响会作用于维生素D内分泌系统，削弱VDR多态性对骨密度和骨转换的影响。我们在德国人群中研究了骨密度、骨折预测性以及骨转换生化标志物与VDR多态性之间的关联。
从164名具有德国种族背景的白种人受试者的异质亚组中采集血液和尿液。采用聚合酶链反应及随后用Bsm I酶切来检测VDR基因型的变异。在初次采集样本后的早晨，测定吡啶啉交联物（Pyr）的尿排泄率和骨碱性磷酸酶（BAP）的血清水平。采用成熟的双能X线吸收法测定骨矿物质密度。
在腰椎和沃德三角区，年龄匹配的VDR BB基因型受试者的骨矿物质密度（90.1±15.5%）低于bb基因型受试者（100.8±10.8%）（分别为91.8±17.9%和101.9±12.1%）。34.2%的BB基因型受试者、14.2%的bB基因型受试者和12.6% bb基因型受试者的Z评分相关骨矿物质密度<85%。典型骨质疏松性骨折部位的骨折率，BB基因型为23.6%，bB基因型为10.8%，bb基因型为0.0%。BB基因型的游离吡啶啉交联物尿排泄率高于bB或bb基因型，但差异不显著。骨碱性磷酸酶未见基因型特异性变异。
作者从本研究得出结论，轴向骨骼的骨矿物质密度与维生素D受体等位基因多态性相关，且对德国亚组人群的骨转换和骨折率有影响。
VDR基因型分析可被视为骨质疏松症诊断难题中的新线索，因为它能为骨折发生率提供预后提示。
