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 3–42% 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 towards understanding bone fragility and the role of intracortical porosity on the strength of bone tissue in children with osteogenesis imperfecta.

Bone Material Properties in Osteogenesis Imperfecta

“…(83,84) Although excessive woven bone is not a clear feature in human OI bone biopsies, increased cortical porosity is, and likely also contributes to increased fracture risk. (85)(86)(87)(88) Fig. 2 summarizes the factors contributing to bone fragility at the different scale lengths.…”

Analyzing the anisotropic Hooke׳s law for children׳s cortical bone

“…Several papers study mechanical properties of children's bone by uniaxial bending (Currey and Butler, 1975;Jans et al, 1998;Davis et al, 2012;Agnew et al, 2013;Berteau et al, 2013;C. I. Albert et al, 2013;Albert et al, 2014), compression (McPherson et al, 2007Ohman et al, 2011) or ultrasonic characterization (Berteau et al, 2012(Berteau et al, , 2013. Some even study mechanical properties at the tissue level by nanoindentation (Fan et al, 2006;Weber et al, 2006;C.…”

New insights in osteocyte imaging by synchrotron radiation

“…Moreover, the bone material properties were not associated significantly with osteocyte lacunar density or volumetric tissue mineral density. 78 Although, no significant association between lacunar density and age in the current paediatric OI population was found. These results are within the range previously observed in young adult bone (e.g., 20,000-90,000 lacunae/mm 3 ).…”

“…Albert et al 78 have described the effects of the Osteogenesis Imperfecta (OI) on osteocyte lacunae density modulation. Twelve cortical bone specimens were collected from long bone diaphysis of nine children with OI.…”