Reconstructing skeletal homeostasis through allogeneic hematopoietic stem cell transplantation in myelofibrosis
Abstract Myeloproliferative neoplasm-associated myelofibrosis is a clonal stem cell process characterized by pronounced bone marrow fibrosis associated with extramedullary hematopoiesis and splenomegaly. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) represents the only curative trea...
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Nature Portfolio
2025-01-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-55915-w |
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| author | Mathias Schäfersküpper Alexander Simon Timur A. Yorgan Felix N. von Brackel Maximilian M. Delsmann Anke Baranowsky Nico Gagelmann Francis Ayuk Thorsten Schinke Michael Amling Nicolaus Kröger Tim Rolvien |
| author_facet | Mathias Schäfersküpper Alexander Simon Timur A. Yorgan Felix N. von Brackel Maximilian M. Delsmann Anke Baranowsky Nico Gagelmann Francis Ayuk Thorsten Schinke Michael Amling Nicolaus Kröger Tim Rolvien |
| author_sort | Mathias Schäfersküpper |
| collection | DOAJ |
| description | Abstract Myeloproliferative neoplasm-associated myelofibrosis is a clonal stem cell process characterized by pronounced bone marrow fibrosis associated with extramedullary hematopoiesis and splenomegaly. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) represents the only curative treatment leading to bone marrow fibrosis regression. Here we provide an in-depth skeletal characterization of myelofibrosis patients before and after allo-HSCT utilizing clinical high-resolution imaging, laboratory analyses, and bone biopsy studies. Despite unimpaired bone microarchitecture at peripheral skeletal sites, we observe a marked increase in bone mineral density at the lumbar spine and proximal femur, which is histologically related to severe bone marrow fibrosis and osteosclerosis, fully normalizing after allo-HSCT. Importantly, the regression of fibrosis is accompanied by vanishing osteosclerosis along with restored osteoclastic resorption activity and whole-body calcium homeostasis. Together, our results provide evidence for an extensive reconstruction of skeletal homeostasis by allo-HSCT in MF, leading to rapid resolution of osteosclerosis. |
| format | Article |
| id | doaj-art-dad4e4cc76b0426298098c803725ec6e |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-dad4e4cc76b0426298098c803725ec6e2025-01-26T12:42:24ZengNature PortfolioNature Communications2041-17232025-01-0116111110.1038/s41467-025-55915-wReconstructing skeletal homeostasis through allogeneic hematopoietic stem cell transplantation in myelofibrosisMathias Schäfersküpper0Alexander Simon1Timur A. Yorgan2Felix N. von Brackel3Maximilian M. Delsmann4Anke Baranowsky5Nico Gagelmann6Francis Ayuk7Thorsten Schinke8Michael Amling9Nicolaus Kröger10Tim Rolvien11Department of Stem Cell Transplantation, University Medical Center Hamburg-EppendorfDepartment of Osteology and Biomechanics, University Medical Center Hamburg-EppendorfDepartment of Osteology and Biomechanics, University Medical Center Hamburg-EppendorfDepartment of Osteology and Biomechanics, University Medical Center Hamburg-EppendorfDepartment of Osteology and Biomechanics, University Medical Center Hamburg-EppendorfDepartment of Osteology and Biomechanics, University Medical Center Hamburg-EppendorfDepartment of Stem Cell Transplantation, University Medical Center Hamburg-EppendorfDepartment of Stem Cell Transplantation, University Medical Center Hamburg-EppendorfDepartment of Osteology and Biomechanics, University Medical Center Hamburg-EppendorfDepartment of Osteology and Biomechanics, University Medical Center Hamburg-EppendorfDepartment of Stem Cell Transplantation, University Medical Center Hamburg-EppendorfDepartment of Osteology and Biomechanics, University Medical Center Hamburg-EppendorfAbstract Myeloproliferative neoplasm-associated myelofibrosis is a clonal stem cell process characterized by pronounced bone marrow fibrosis associated with extramedullary hematopoiesis and splenomegaly. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) represents the only curative treatment leading to bone marrow fibrosis regression. Here we provide an in-depth skeletal characterization of myelofibrosis patients before and after allo-HSCT utilizing clinical high-resolution imaging, laboratory analyses, and bone biopsy studies. Despite unimpaired bone microarchitecture at peripheral skeletal sites, we observe a marked increase in bone mineral density at the lumbar spine and proximal femur, which is histologically related to severe bone marrow fibrosis and osteosclerosis, fully normalizing after allo-HSCT. Importantly, the regression of fibrosis is accompanied by vanishing osteosclerosis along with restored osteoclastic resorption activity and whole-body calcium homeostasis. Together, our results provide evidence for an extensive reconstruction of skeletal homeostasis by allo-HSCT in MF, leading to rapid resolution of osteosclerosis.https://doi.org/10.1038/s41467-025-55915-w |
| spellingShingle | Mathias Schäfersküpper Alexander Simon Timur A. Yorgan Felix N. von Brackel Maximilian M. Delsmann Anke Baranowsky Nico Gagelmann Francis Ayuk Thorsten Schinke Michael Amling Nicolaus Kröger Tim Rolvien Reconstructing skeletal homeostasis through allogeneic hematopoietic stem cell transplantation in myelofibrosis Nature Communications |
| title | Reconstructing skeletal homeostasis through allogeneic hematopoietic stem cell transplantation in myelofibrosis |
| title_full | Reconstructing skeletal homeostasis through allogeneic hematopoietic stem cell transplantation in myelofibrosis |
| title_fullStr | Reconstructing skeletal homeostasis through allogeneic hematopoietic stem cell transplantation in myelofibrosis |
| title_full_unstemmed | Reconstructing skeletal homeostasis through allogeneic hematopoietic stem cell transplantation in myelofibrosis |
| title_short | Reconstructing skeletal homeostasis through allogeneic hematopoietic stem cell transplantation in myelofibrosis |
| title_sort | reconstructing skeletal homeostasis through allogeneic hematopoietic stem cell transplantation in myelofibrosis |
| url | https://doi.org/10.1038/s41467-025-55915-w |
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