Reid D M, Mackay I, Wilkinson S, Miller C, Schuette D G, Compston J, Cooper C, Duncan E, Galwey N, Keen R, Langdahl B, McLellan A, Pols H, Uitterlinden A, O'Riordan J, Wass J A H, Ralston S H, Bennett S T
Department of Medicine and Therapeutics, Medical School, University of Aberdeen, Foresterhill, Aberdeen, AB25 2ZD, UK.
Osteoporos Int. 2006 Jan;17(1):125-32. doi: 10.1007/s00198-005-1936-y. Epub 2005 Sep 1.
Osteoporosis is a common disease with a strong genetic component characterized by reduced bone mass and an increased risk of fragility fractures. Bone mineral density (BMD) is the most important determinant of osteoporotic fracture risk, but the genes responsible for BMD regulation and fracture are incompletely defined. To enable multi-center studies to examine the genetic influences on BMD there is a requirement to standardize measurements across different manufacturers of bone densitometers, different versions of machines and different normative ranges. This paper describes a method developed to allow near-identical subjects with low age-adjusted BMD (based on Z-scores) to be recruited in 17 centers using 27 different densitometers. Cross-calibration was based on measurements using a European spine phantom circulated to all centers and measured ten times on each individual machine. From theses values an individual exponential curve, based on nominal versus observed BMD, was derived for each machine. As expected, there were large and significant variations in nominal BMD values, not only between scanners from different manufacturers but also between different versions of scanners from the same manufacturer. Hologic scanners tended to underestimate the nominal BMD, while Lunar scanners overestimated the value. Norland scanners gave mixed values over estimating BMD at the lower nominal value (0.5 g/cm2) while underestimating the value at the higher value (1.5 g/cm2). The validity of the exponential equations was tested using hip and spine measurements on 991 non-proband women from a familial osteoporosis study (FAMOS). After cross-calibration there was a considerable reduction in variation between machines. This observation, coupled with the absence of a similar reduction in variation attributable to a linear regression on age, demonstrated the validity of the cross-calibration approach. Use of the cross-calibration curves along with a standard normative range (in the case of this study, the Hologic normative range) allowed age-specific Z-scores to be used as an inclusion criterion in this genetic study, a method that will be useful for other trials where age-specific BMD inclusion criteria are required.
骨质疏松症是一种常见疾病，具有很强的遗传因素，其特征是骨量减少和脆性骨折风险增加。骨密度（BMD）是骨质疏松性骨折风险的最重要决定因素，但负责BMD调节和骨折的基因尚未完全明确。为了使多中心研究能够检查基因对BMD的影响，需要对不同制造商的骨密度仪、不同版本的机器以及不同的正常范围进行测量标准化。本文描述了一种开发的方法，该方法允许在17个中心使用27种不同的骨密度仪招募年龄调整后BMD较低（基于Z评分）的近乎相同的受试者。交叉校准基于使用分发给所有中心的欧洲脊柱模型进行的测量，并在每台单独的机器上测量十次。根据这些值，为每台机器得出基于标称BMD与观察到的BMD的个体指数曲线。正如预期的那样，标称BMD值存在很大且显著的差异，不仅在不同制造商的扫描仪之间，而且在同一制造商的不同版本扫描仪之间。Hologic扫描仪往往低估标称BMD，而Lunar扫描仪则高估该值。Norland扫描仪给出的混合值在较低标称值（0.5 g/cm²）时高估BMD，而在较高值（1.5 g/cm²）时低估该值。使用来自家族性骨质疏松症研究（FAMOS）的991名非先证者女性的髋部和脊柱测量结果对指数方程的有效性进行了测试。交叉校准后，机器之间的差异大幅减少。这一观察结果，再加上因年龄线性回归导致的差异没有类似减少，证明了交叉校准方法的有效性。使用交叉校准曲线以及标准正常范围（在本研究中为Hologic正常范围），使得特定年龄的Z评分能够用作该基因研究的纳入标准，该方法将对其他需要特定年龄BMD纳入标准的试验有用。
