Secondary osteopenia following allogeneic bone marrow or stem cell transplantation (BMT or HSCT) is a significant source of morbidity in patients. It is believed to be caused by a number of factors related to the myeloablative conditioning and subsequent therapy regimen. We here aimed to investigate whether the allogeneic bone marrow by itself directly impacts on the bone mass of the patient. We thus performed syn- and allogeneic BMT between two inbred mouse strains, which share an identical major histocompatibility complex background yet differ in their bone phenotypes. BMT was well tolerated, yielded survival rates of 97% and allowed for a regular physiological development. However, allogeneic BMT led to a significant reduction of trabecular bone mass that was independent of strain, sex, immunosuppressive medication, complications resulting from graft versus host disease, underlying bone phenotype and numbers of osteoclasts. Instead, reduced trabecular bone mass correlated with reduced plasma levels of amino-terminal propeptide of type I collagen. Our results suggest that osteopenia following allogeneic BMT is significantly influenced by an impaired osteoblast activity that may stem from a lack of communication between the resident osteoblasts and an allogeneic bone marrow-derived cell type. Elucidating this incompatibility will open new approaches for the therapy of secondary osteopenia.
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The authors wish to thank Ilona Klamfuß and Karin Gerber (Institute of Experimental Surgery) for taking excellent care of the mice. This study was funded by an intramural grant (FORUN_Os). AO was funded by a fellowship from the federal state of Mecklenburg-Vorpommern and Rostock University Medical Center.
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The authors declare no conflict of interest.
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Osterberg, A., Engelmann, R. & Müller-Hilke, B. Allogeneic yet major histocompatibility complex-matched bone marrow transplantation in mice results in an impairment of osteoblasts and a significantly reduced trabecular bone. J Bone Miner Metab 36, 420–430 (2018). https://doi.org/10.1007/s00774-017-0859-y
- Allogeneic and syngeneic bone marrow transfer
- Bone remodeling