An approach for determining quantitative measures for bone volume and bone mass in the pediatric spina bifida population

Abstract

Background: The pediatric spina bifida population suffers from decreased mobility and recurrent fractures. This study aimed to develop a method for quantifying bone mass along the entire tibia in youth with spina bifida. This will provide information about all potential sites of bone deficiencies.

Methods: Computed tomography images of the tibia for 257 children (n=80 ambulatory spina bifida, n=10 non-ambulatory spina bifida, n=167 typically developing) were analyzed. Bone area was calculated at regular intervals along the entire tibia length and then weighted by calibrated pixel intensity for density weighted bone area. Integrals of density weighted bone area were used to quantify bone mass in the proximal and distal epiphyses and diaphysis. Group differences were evaluated using analysis of variance.

Findings: Non-ambulatory children suffer from decreased bone mass in the diaphysis and proximal and distal epiphyses compared to ambulatory and control children (P≤0.001). Ambulatory children with spina bifida showed statistically insignificant differences in bone mass in comparison to typically developing children at these sites (P>0.5).

Interpretation: This method provides insight into tibial bone mass distribution in the pediatric spina bifida population by incorporating information along the whole length of the bone, thereby providing more information than dual-energy x-ray absorptiometry and peripheral quantitative computed tomography. This method can be applied to any population to assess bone mass distribution across the length of any long bone.

Keywords: Bone density; Bone mass; Image analysis; Myelomeningocele; Spina bifida.

Figure 1

A) CT-image of a control child before image processing; B) An ROI has been defined in the diaphysis and the same CT-image slice has been filtered to remove noise, and aligned in BoneJ; C) This image illustrates the application of the 206 HU threshold on the CT-image in (B); D) An ROI has been defined in the proximal epiphysis and the same CT-image slice has been filtered to remove noise, and aligned in BoneJ; E) This image illustrates the application of the 206 HU threshold on the CT-image in (D).

Figure 2

Normalized bone area (nBA) of a control child (7.8 years old) across the entire normalized length of the tibia. The epiphyseal and diaphyseal regions are labeled as well as the growth plates in the epiphyses.

Figure 3

Mean normalized bone area (nBA) and normalized density-weighted bone area (nDWBA) across normalized slice position for the control, AmbSB and Non-AmbSB groups.

Figure 4

The integral of normalized bone area (nBA) as a representation of normalized bone volume in the epiphyses and diaphysis. For each group, boxplots show the median (red line), 25^th and 75^th percentiles (lower and upper edges of blue box), maximum and minimum non-outliers (whiskers) and outliers (red points). Data points are considered outliers if they greater than [q₃+1.5(q₃−q₁)] or smaller than [q₁ −1.5(q₃−q₁)], where q₃ and q₁ and the 75^th and 25^th percentiles respectively. Brackets above the boxplots indicate statistically significant differences between control, AmbSB and Non-AmbSB groups (*P≤0.05,**P≤0.01,***P≤0.001).

Figure 5

The integral of normalized density-weighted bone area (nDWBA) as a representation of normalized bone mass in the epiphyses and diaphysis. For each group, boxplots show the median (red line), 25^th and 75^th percentiles (lower and upper edges of blue box), maximum and minimum non-outliers (whiskers) and outliers (red points). Data points are considered outliers if they greater than [q₃+1.5(q₃−q₁)] or smaller than [q₁ −1.5(q₃−q₁)], where q₃ and q₁ and the 75^th and 25^th percentiles respectively. Statistically significant differences between control, AmbSB and Non-AmbSB groups are shown (***P≤0.001).