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

Abstract

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.

Collagen proton fraction from ultrashort echo time magnetization transfer (UTE‐MT) MRI modelling correlates significantly with cortical bone porosity measured with micro‐computed tomography (μCT)

“…BMD and T 1 showed significant increases from the inner layer towards the outer layer ( p < 0.01). Such results were in agreement with the multiple previous studies that have shown lower intracortical porosity and pore size on the periosteal side compared with the endosteal side, using a variety of methods including high‐resolution microscopy, histology, and high‐resolution quantitative CT …”

“…BMD and T 1 showed significant increases from the inner layer towards the outer layer (p < 0.01). Such results were in agreement with the multiple previous studies that have shown lower intracortical porosity and pore size on the periosteal side compared with the endosteal side, using a variety of methods including high-resolution microscopy, histology, and high-resolution quantitative CT. [42][43][44][45] The results of this study suggested that MMF from UTE-MT modeling is a useful and promising surrogate for assessing human intracortical porosity and BMD in particular for specimens from donors with no known bone disease. This MRI based technique is non-invasive, x-ray free, and importantly translatable to in vivo studies.…”

Use of backscattered scanning electron microscopy to quantify the bone tissues of mid‐thoracic human ribs

“…Similarly, osteoblast apoptosis triggered by sex steroid withdrawal may result in reduced osteocyte densities (i.e., fewer cells to differentiate into mature osteocytes) after menopause (Bradford, Gerace, Roland, & Chrzan, ). While the women in our study demonstrate greater lacunar abundance across the entire adult lifespan compared to men, the lack of significant relationships with age supports a paradigm shift away from estrogen‐centric effects on this aspect of bone quality (Hunter & Agnew, ; Manolagas & Parfitt, ). In agreement, Qiu et al (2002b) also did not find a relationship between osteocyte lacunar density (Ot.Lc.Dn) and the menopause transition.…”

“…Early work suggested that the ratio of Ct.Po to bone area remains relatively constant across the adult lifespan in the human rib (Frost, 1963); however, this assertion has been contested. Newer research has not identified any sex‐based differences, but studies demonstrate a linear increase in Ct.Po with age (Dominguez & Agnew, ; Hunter & Agnew, ). This relationship has been described to varying degrees in men and women at other anatomical locations (Bach‐Gansmo et al, ; Bousson et al, ; Brockstedt, Kassem, Eriksen, Mosekilde, & Melsen, ; Burghardt et al, ; Feik, Thomas, & Clement, ; Hansen et al, ; Kazakia et al, ; Macdonald et al, ; Vilayphiou, Boutroy, Sornay‐Rendu, Rietbergen, & Chapurlat, ), but direct comparisons to our results may not be appropriate given differences in mechanical loading between skeletal elements.…”

“…Osteoporotic bone has been found to contain fewer osteocyte lacunae than controls (Busse et al, ; Mullender, Tan, Vico, Alexandre, & Klein‐Nulend, ; Qiu, Rao, Palnitkar, & Parfitt, ; Zarrinkalam, Mulaibrahimovic, Atkins, & Moore, ), although this relationship is somewhat controversial (Mullender, Van Der Meer, Huiskes, & Lips, ; Oliveira et al, ). Numerous studies report age‐related declines in Ot.Lc.Dn to varying degrees in both sexes (Bach‐Gansmo et al, ; Bernhard et al, ; Busse et al, ; Hunter & Agnew, ; Mullender et al, , ; Qiu, Rao, Palnitkar, & Parfitt, , , ; Vashishth, Gibson, Kimura, Schaffler, & Fyhrie, ). However, others have also demonstrated the inverse relationship (Vashishth, Gibson, & Fyhrie, ), or no relationship at all (Carter et al, , ).…”