Blouin, S. | Search bioRxiv

bioRxiv2024

The mineralization of osteonal cement line depends on where the osteon is formed

The cement line (CL) is a thin layer separating secondary osteons from interstitial bone and other osteons. It is assumed to play a significant role in bone fracture resistance, owing to its ability to deflect or arrest microcracks. Despite the possible role for bone quality, the CL is still one of the least understood microstructural features of bones, with unknowns on CL composition, mineralization, and mechanical properties. This study, focusing on CL mineralization, aims to elucidate the interplay between the mineral content of the CL and of adjacent bone tissue. Using quantitative backscattered electron imaging, osteons with different degrees of mineralization coming from human femoral samples were analyzed. We implemented a spatially resolved analysis of the mineral content in layers along the CL, considering both regions inside the osteon (i.e., formed soon after CL deposition) and outside (i.e., already present at the time of CL deposition). We found that the mineral content of the CL correlates strongly with the mineral content outside of the osteon, but not inside. Assuming the mineral content of the osteon as a proxy of its age, we demonstrate that not only the osteon, but also the CL increases its mineral content with time. However, the rate of increase is lower in the CL. Importantly, the specific value of the high initial mineral content of the CL depends on the mineral content of the local surrounding, in which the osteon was formed. Our findings highlight the central role of the local degree of mineralization of the bone around the osteon for building the CL.

bioengineering↗

bioRxiv2023

3D osteocyte lacunar morphometry of human bone biopsies with high resolution microCT: from monoclonal gammopathy to newly diagnosed multiple myeloma

Osteocytes are mechanosensitive, bone-embedded cells which are connected via dendrites in a lacuno-canalicular network and regulate bone resorption and formation balance. Alterations in osteocyte lacunar volume, shape and density have been identified in conditions of aging, osteoporosis and osteolytic bone metastasis, indicating patterns of impaired bone remodeling, osteolysis and disease progression. Osteolytic bone disease is a hallmark of the hematologic malignancy multiple myeloma (MM), in which monoclonal plasma cells in the bone marrow disrupt the bone homeostasis and induce excessive resorption at local and distant sites. Qualitative and quantitative changes in the 3D osteocyte lacunar morphometry have not yet been evaluated in MM, nor in the precursor conditions monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM). In this study, we characterized the osteocyte lacunar morphology in trabecular bone of the iliac crest at the ultrastructural level using high resolution microCT in human bone biopsy samples of three MGUS, two SMM and six newly diagnosed MM. In MGUS, SMM and MM we found a trend for lower lacunar density and a shift towards larger lacunae with disease progression (higher 50% cutoff of the lacunar volume cumulative distribution) in the small osteocyte lacunae 20-900 m3 range compared to control samples. In the larger lacunae 900-3000 m3 range, we detected significantly higher lacunar density and microporosity in the MM group compared to the MGUS/SMM group. Regarding the shape distribution, the MGUS/SMM group showed a trend for flatter, more elongated and anisotropic osteocyte lacunae compared to the control group. Altogether, our findings suggest that osteocytes in human MM bone disease undergo changes in their lacunae density, volume and shape, which could be an indicator for osteolysis and disease progression. Future studies are needed to understand whether alterations of the lacunae architecture affect the mechanoresponsiveness of osteocytes and ultimately bone adaptation and fracture resistance in MM and its precursors conditions.

bioengineering↗