Reduced diaphyseal strength associated with high intracortical vascular porosity within long bones of children with osteogenesis imperfecta

Abstract

Osteogenesis imperfecta is a genetic disorder resulting in bone fragility. The mechanisms behind this fragility are not well understood. In addition to characteristic bone mass deficiencies, research suggests that bone material properties are compromised in individuals with this disorder. However, little data exists regarding bone properties beyond the microstructural scale in individuals with this disorder. Specimens were obtained from long bone diaphyses of nine children with osteogenesis imperfecta during routine osteotomy procedures. Small rectangular beams, oriented longitudinally and transversely to the diaphyseal axis, were machined from these specimens and elastic modulus, yield strength, and maximum strength were measured in three-point bending. Intracortical vascular porosity, bone volume fraction, osteocyte lacuna density, and volumetric tissue mineral density were determined by synchrotron micro-computed tomography, and relationships among these mechanical properties and structural parameters were explored. Modulus and strength were on average 64-68% lower in the transverse vs. longitudinal beams (P<0.001, linear mixed model). Vascular porosity ranged between 3 and 42% of total bone volume. Longitudinal properties were associated negatively with porosity (P≤0.006, linear regressions). Mechanical properties, however, were not associated with osteocyte lacuna density or volumetric tissue mineral density (P≥0.167). Bone properties and structural parameters were not associated significantly with donor age (P≥0.225, linear mixed models). This study presents novel data regarding bone material strength in children with osteogenesis imperfecta. Results confirm that these properties are anisotropic. Elevated vascular porosity was observed in most specimens, and this parameter was associated with reduced bone material strength. These results offer insight toward understanding bone fragility and the role of intracortical porosity on the strength of bone tissue in children with osteogenesis imperfecta.

Keywords: Flexural properties; Intracortical porosity; Osteogenesis imperfecta; Pediatric bone; Strength.

Figure 1

Flexural load-displacement curves for beams of bone oriented longitudinally (black) and transversely (grey) to the long bone axis. These beams were obtained from the humeral diaphysis of an 8 year-old female donor with OI type IV (specimen 5).

Figure 2

Three-dimensional tomographic assessment of OI cortical bone structure. SR-µCT images of OI bone show vascular porosity in longitudinal (top, left; vascular porosity = 16%) and transverse (top, right; vascular porosity = 21%) beams from the femoral mid-diaphysis of a 3 year-old female (donor 6) with OI type III. Idealized drawings of longitudinal (bottom, left) and transverse (bottom, right) beams, along with corresponding tomographic slices, illustrate the predominant orientation of osteons in each beam. Although both orientations displayed a similarly high degree of vascular porosity (16% for the longitudinal beam and 21% for the transverse one), the longitudinally oriented beam had much higher strength than did the transverse one (maximum flexural strength were 78 vs. 15 MPa, respectively).

Figure 3

Linear relationships between elastic modulus (E) and intracortical vascular porosity for OI bone oriented longitudinally (black diamonds) and transversely (white triangles) to the long diaphyseal axis.