Importance of Technique for Determination of Phenotype

Vicente Gilsanz

Radiology Department Children’s Hospital Los Angeles Los Angeles, California 90027

As C. Tao et al. acknowledge, the discrepancy in results between their and our studies could be due to the different techniques used to assess "bone density." Whereas CT values reflect the volumetric density of cancellous bone in the vertebral bodies, dual energy x-ray absorptiometry (DXA) measurements are influenced not only by the density of the bone, but also by a large number of biological parameters (1). The title of the study by Tao et al. would be more correctly stated as "No association was found between collagen {alpha}I type 1 gene and DXA bone measurements obtained in prepubertal children."

DXA is a projection technique and its measurements are based on the two-dimensional projection of a three-dimensional structure. Thus, DXA values are a function of three skeletal parameters: the size of the bone being examined, the volume of the bone (cancellous and cortical), and its mineral density (2). These values are frequently expressed as measurements of the bone content per surface area (gm/cm2), as determined by scan radiographs. However, scan radiographs only provide an approximation of the size of the bone, and any correction based on these radiographs is only a very rough estimate of the "density." In addition, DXA values are influenced by the unknown composition of soft tissues in the beam path of the region of interest. Because corrections for the soft tissues are based on a homogenous distribution of fat around the bone, changes in DXA measurements are observed if fat is distributed inhomogeneously. It has been determined that inhomogeneous fat distribution in soft tissues, resulting in a difference of 2-cm fat layer between soft tissue area and bone area, will influence DXA measurements by 10% (3).

These technical limitations may account for the difference between our results with computed tomography and those of Tao et al. using DXA. They also likely explain the variability in the results of previous absorptiometry studies on other genetic determinants of bone acquisition during growth, such as race and gender. Whereas some published data using DXA report that there are no differences in bone acquisition between black and white girls, others indicate higher values for black girls at all ages (4, 5, 6, 7). Similarly, studies using DXA have found that vertebral bone mass is greater in girls than in boys, that there are no gender differences in vertebral bone mass, and that vertebral bone mass is greater in boys than in girls (8, 9, 10, 11, 12, 13). In this vein, the results of Tao et al. suggest that girls have higher vertebral bone mass, but lower femoral bone mass, than boys. These findings are in direct contrast to another recent study by our group using computed tomography (14).

Progress in analyzing the genetic factors that contribute to bone mass acquisition in children has been modest. Advances will remain slow if we persist in using techniques that do not allow for three-dimensional comparative studies of the different structural parameters that account for the large degree of genetic variation in skeletal development.

References

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  14. Gilsanz V, Kovanlikaya A, Costin G, Roe TF, Sayre J, Kaufman F. 1997 Differential effect of gender on the size of the bones in the axial and appendicular skeletons. J Clin Endocrinol Metab. 82:1603–1607.[Abstract/Free Full Text]




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