Age-Related Increases in Marrow Fat Volumes have Regional Impacts on Bone Cell Numbers and Structure

Abstract

The increasing levels of bone marrow fat evident in aging and osteoporosis are associated with low bone mass and attributed to reduced osteoblastogenesis. Local lipotoxicity has been proposed as the primary mechanism driving this reduction in bone formation. However, no studies have examined the correlation between high levels of marrow fat volumes and changes in local cellularity. In this study, we hypothesize that areas of bone marrow with high fat volumes are associated with significant changes in cell number within a similar region of interest (ROI). Inbred albino Louvain (LOU) rats, originating from the Wistar strain, have been described as a model of healthy aging with the absence of obesity but expressing the typical features of age-related bone loss. We compared local changes in distal femur cellularity and structure in specific ROI of undecalcified bone sections from 4- and 20-month-old male and female LOU rats and Wistar controls. Our results confirmed that older LOU rats exhibited significantly higher fat volumes than Wistar rats (p < 0.001). These higher fat volume/total volume were associated with lower trabecular number (p < 0.05) and thickness (p < 0.05) and higher trabecular separation (p < 0.05). In addition, osteoblast and osteocyte numbers were reduced in the similar ROI containing high levels of adiposity, while osteoclast number was higher compared to control (p < 0.03). In summary, marrow ROIs with a high level of adiposity were associated with a lower bone mass and changes in cellularity explaining associated bone loss. Further studies assessing the levels of lipotoxicity in areas of high local marrow adiposity and identifying molecular actors involved in this phenomenon are still required.

Keywords: LOU rats; Marrow adipose tissue; Osteoblast; Osteoclast; Osteoporosis.