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

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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.

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Acknowledgements

This work was supported by a catalyst grant on aging research from the Canadian Institutes of Health Research (CIHR; Grant 200703IAP) to GD, GF, PG, JH and FR and a pilot project grant from the Quebec Network for Research on Aging, a network funded by the Fonds de Recherche du Québec-Santé. LLC holds a travel grant from the Australian Institute for Musculoskeletal Science (AIMSS).

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Authors and Affiliations

  1. Australian Institute for Musculoskeletal Science (AIMSS), The University of Melbourne and Western Health, 176 Furlong Road, St. Albans, VIC, 3021, Australia

    Ahmed Al Saedi, Lulu Chen, Steven Phu & Gustavo Duque

  2. Department of Medicine-Western Health, Melbourne Medical School, The University of Melbourne, St. Albans, VIC, Australia

    Ahmed Al Saedi, Steven Phu, Sara Vogrin & Gustavo Duque

  3. Department of Anatomy, Histology and Embryology, Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China

    Lulu Chen & Dengshun Miao

  4. Département de Nutrition, Faculté de médecine de l′université de Montréal (UdeM) and Centre de Recherche de L′Institut de Cardiologie de Montréal, Montréal, QC, Canada

    Guylaine Ferland

  5. Département de médecine, UdeM and Laboratoire de Neuroendocrinologie du Vieillissement, Centre de Recherche du Centre Hospitalier de l′université de Montreal (UdeM), 900 rue Saint-Denis, Pavillon R, Montréal, QC, Canada

    Pierrette Gaudreau

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  1. Ahmed Al Saedi
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Contributions

All authors contributed to the study conception and design and material preparation. Data collection and analysis were performed by AAS and LC. The first draft of the manuscript was written by AAS and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Gustavo Duque.

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Ahmed Al Saedi, Lulu Chen, Steven Phu, Sara Vogrin, Dengshun Miao, Guylaine Ferland, Pierrette Gaudreau, and Gustavo Duque declare that they have no competing interest.

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All animal protocols were approved by the Animal Care Committee of CHUM Research Center in compliance with guidelines of the Canadian Council for Animal Care.

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Al Saedi, A., Chen, L., Phu, S. et al. Age-Related Increases in Marrow Fat Volumes have Regional Impacts on Bone Cell Numbers and Structure. Calcif Tissue Int 107, 126–134 (2020). https://doi.org/10.1007/s00223-020-00700-8

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