Reconstructing skeletal homeostasis through allogeneic hematopoietic stem cell transplantation in myelofibrosis

Nat Commun. 2025 Jan 20;16(1):741. doi: 10.1038/s41467-025-55915-w.

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.

MeSH terms

  • Adult
  • Aged
  • Bone Density
  • Bone Marrow / pathology
  • Bone and Bones / pathology
  • Calcium / metabolism
  • Female
  • Femur / diagnostic imaging
  • Femur / pathology
  • Hematopoietic Stem Cell Transplantation*
  • Homeostasis*
  • Humans
  • Male
  • Middle Aged
  • Osteosclerosis* / diagnostic imaging
  • Osteosclerosis* / metabolism
  • Primary Myelofibrosis* / metabolism
  • Primary Myelofibrosis* / pathology
  • Primary Myelofibrosis* / therapy
  • Transplantation, Homologous*

Substances

  • Calcium