Intraskeletal variation in human cortical osteocyte lacunar density: Implications for bone quality assessment

Osteocytes and their lacunocanalicular network have been identified as the regulator of bone quality and function by exerting extensive influence over metabolic processes, mechanical adaptation, and mineral homeostasis. Recent research has shown that osteocyte apoptosis leads to a decrease in bone quality and increase in bone fragility mediated through its effects on remodeling. The purpose of this study is to investigate variation in cortical bone osteocyte lacunar density with respect to major factors including sex, age, and intracortical porosity to establish both regional and systemic trends. Samples from the midshaft femur, midshaft rib and distal one-third diaphysis of the radius were recovered from 30 modern cadaveric individuals (15 males and 15 females) ranging from 49 to 100 years old. Thick ground undecalcified histological (80 μm) cross-sections were made and imaged under bright field microscopy. Osteocyte lacunar density (Ot.Lc.N/B.Ar) and intracortical porosity (%Po.Ar) were quantified. No significant sex differences in Ot.Lc.N/B.Ar or %Po.Ar were found in any element. Linear regressions demonstrated a significant decrease in osteocyte lacunar density (Ot.Lc.N/B.Ar) and increase in intracortical porosity (%Po.Ar) with age for the sex-pooled sample in the femur (R2 = 0.208, 0.297 respectively) and radius (R2 = 0.108, 0.545 respectively). Age was unable to significantly predict osteocyte lacunar density or intracortical porosity in the rib (R2 = 0.058, 0.114 respectively). Comparisons of regression coefficients demonstrated a systemic trend in the decrease in osteocyte lacunar density (Ot.Lc.N/B.Ar) and increase in intracortical porosity (%Po.Ar) with age. In each element, intracortical porosity was significantly negatively correlated with lacunar density for which the radius demonstrated the strongest relationship (r = −0.746). Using pore number (Po.N) as a proxy for available vascularity to support the osteocyte population, Po.N was able to predict 61.8% of variation in osteocyte lacunar number (Ot.Lc.N) in the rib. The femur and radius also demonstrated significant relationships between these variables (R2 = 0.560 and 0.397 respectively). The results from this study indicate that although the femur, radius and rib may be experiencing systemically influenced declines in osteocyte lacunar density, there may be differential effects at each anatomical site potentially due to age related changes in mechanical loading. With decreasing osteocyte lacunar density in each element, intracortical porosity increased with likely direct impacts on gross bone strength. This study provides a foundation upon which to build interpretations of osteocyte lacunar density values and their effect on differential fracture risk for aging individuals. Keywords: Osteocyte, Osteocyte lacunar density, Cortical bone, Intracortical porosity, Bone qualit