Reconstructing skeletal homeostasis through allogeneic hematopoietic stem cell transplantation in myelofibrosis

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 () and Tim Rolvien ()
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Mathias Schäfersküpper: University Medical Center Hamburg-Eppendorf
Alexander Simon: University Medical Center Hamburg-Eppendorf
Timur A. Yorgan: University Medical Center Hamburg-Eppendorf
Felix N. von Brackel: University Medical Center Hamburg-Eppendorf
Maximilian M. Delsmann: University Medical Center Hamburg-Eppendorf
Anke Baranowsky: University Medical Center Hamburg-Eppendorf
Nico Gagelmann: University Medical Center Hamburg-Eppendorf
Francis Ayuk: University Medical Center Hamburg-Eppendorf
Thorsten Schinke: University Medical Center Hamburg-Eppendorf
Michael Amling: University Medical Center Hamburg-Eppendorf
Nicolaus Kröger: University Medical Center Hamburg-Eppendorf
Tim Rolvien: University Medical Center Hamburg-Eppendorf

Nature Communications, 2025, vol. 16, issue 1, 1-11

Abstract: 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.

Date: 2025
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DOI: 10.1038/s41467-025-55915-w

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