Alterations of Mass Density and 3D Osteocyte Lacunar Properties in Bisphosphonate-Related Osteonecrotic Human Jaw Bone, a Synchrotron µCT Study

Abstract

Osteonecrosis of the jaw, in association with bisphosphonates (BRONJ) used for treating osteoporosis or cancer, is a severe and most often irreversible side effect whose underlying pathophysiological mechanisms remain largely unknown. Osteocytes are involved in bone remodeling and mineralization where they orchestrate the delicate equilibrium between osteoclast and osteoblast activity and through the active process called osteocytic osteolysis. Here, we hypothesized that (i) changes of the mineralized tissue matrix play a substantial role in the pathogenesis of BRONJ, and (ii) the osteocyte lacunar morphology is altered in BRONJ. Synchrotron µCT with phase contrast is an appropriate tool for assessing both the 3D morphology of the osteocyte lacunae and the bone matrix mass density. Here, we used this technique to investigate the mass density distribution and 3D osteocyte lacunar properties at the sub-micrometer scale in human bone samples from the jaw, femur and tibia. First, we compared healthy human jaw bone to human tibia and femur in order to assess the specific differences and address potential explanations of why the jaw bone is exclusively targeted by the necrosis as a side effect of BP treatment. Second, we investigated the differences between BRONJ and control jaw bone samples to detect potential differences which could aid an improved understanding of the course of BRONJ. We found that the apparent mass density of jaw bone was significantly smaller compared to that of tibia, consistent with a higher bone turnover in the jaw bone. The variance of the lacunar volume distribution was significantly different depending on the anatomical site. The comparison between BRONJ and control jaw specimens revealed no significant increase in mineralization after BP. We found a significant decrease in osteocyte-lacunar density in the BRONJ group compared to the control jaw. Interestingly, the osteocyte-lacunar volume distribution was not altered after BP treatment.

Osteocyte lacunar properties in rat cortical bone: Differences between lamellar and central bone

“…Indeed, it is well established that bone is a complex three-dimensional material, and probing such structures is best achieved using 3D methods such as synchrotron radiation µCT. Despite using 3D methods, large variations in osteocyte lacunar properties are reported, indicating a natural morphological heterogeneity in osteocyte populations (Buenzli and Sims, 2015;Carter et al, 2014;Hesse et al, 2014b). Furthermore, the lacunocanalicular network organization in lamellar bone has been reported to be closely coupled to that of the extracellular matrix (Kerschnitzki et al, 2011;Reznikov et al, 2014a;Reznikov et al, 2013).…”

High-resolution 3D imaging of osteocytes and computational modelling in mechanobiology: insights on bone development, ageing, health and disease

“…In a recent FE study human bone was imaged using synchrotron X-ray phase nanotomography at a voxel size of 50 nm (Varga et al, 2014). The LCN morphology was quantified and the osteocyte and processes artificially reconstructed using a priori assumptions from TEM and CLSM studies to approximate cell shape, canalicular occupation as well as PCM and osteocyte process dimensions.…”

Distribution of mesoscale elastic properties and mass density in the human femoral shaft

“…An alternative approach is the direct comparison of synchrotron attenuation and refractive index values. The latter can be reconstructed by the recently developed phase contrast tomography (59,60). Such comparison should be addressed in future studies.…”