Hutchinson-Gilford progeria is a skeletal dysplasia

Abstract

Hutchinson-Gilford progeria syndrome (HGPS) is a rare segmental premature aging disorder that affects bone and body composition, among other tissues. We sought to determine whether bone density and structural geometry are altered in children with HGPS and whether relationships exist among these parameters and measures of skeletal anthropometry, body composition, and nutrition. We prospectively enrolled 26 children with HGPS (ages 3.1 to 16.2 years). Outcomes included anthropometric data; bone age; areal bone mineral density (aBMD) and body composition by dual-energy X-ray absorptiometry (DXA); volumetric bone mineral density (vBMD), strength-strain index (SSI), and bone structural rigidity calculated from radial transaxial peripheral quantitative computed tomographic (pQCT) images; serum bone biomarkers and hormonal measures; and nutrition assessments. Children with HGPS had low axial aBMD Z-scores by DXA, which improved after adjustment for height age, whereas differences in radial vBMD by pQCT were less striking. However, pQCT revealed distinct abnormalities in both novel measures of bone structural geometry and skeletal strength at the radius compared with healthy controls. Dietary intake was adequate, confirming that HGPS does not represent a model of malnutrition-induced bone loss. Taken together, these findings suggest that the phenotype of HGPS represents a unique skeletal dysplasia.

Figure 1. Skeletal Sites Assessed via Peripheral Quantitative Computed Tomography

Cross-sectional measures were obtained 4, 20, 50 and 66% distance from distal growth plate.

Figure 2. Differences in Bone Structure and Geometry in Patients with Hutchinson-Gilford Progeria Syndrome (HGPS) vs. Healthy Controls

This figure outlines some of the unusual cross-sectional geometries observed in the HGPS patients. The left panel highlights a “star” shaped cross-section for the radius and ulna at 20% distance from the distal growth plate, in comparison to the more elliptical cross-sections of the bones from a control subject. The panel on the right denotes a tailed ulnar cross-section at a distance 66% from the distal growth plate, where the medullary cavity is filled with bone. This is in sharp contrast to the site matched cross-section from a control subject.

Figure 3. Differences in Skeletal Rigidity in Patients with HGPS vs. Healthy Controls

Means and standard deviations for A) cross-sectional axial (EA), B) bending (EI) and C) torsional (GJ) rigidities and D) total vBMD at indicated radial sites in patients with HGPS (white bars) and matched control patients (grey bars). ^* indicates p<0.0001.