Schäfersküpper Mathias, Simon Alexander, Yorgan Timur A, von Brackel Felix N, Delsmann Maximilian M, Baranowsky Anke, Gagelmann Nico, Ayuk Francis, Schinke Thorsten, Amling Michael, Kröger Nicolaus, Rolvien Tim
Department of Stem Cell Transplantation, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Department of Osteology and Biomechanics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Nat Commun. 2025 Jan 20;16(1):741. doi: 10.1038/s41467-025-55915-w.
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.
骨髓增殖性肿瘤相关的骨髓纤维化是一种克隆性干细胞疾病，其特征为明显的骨髓纤维化，并伴有髓外造血和脾肿大。异基因造血干细胞移植（allo-HSCT）是导致骨髓纤维化消退的唯一治愈性治疗方法。在此，我们利用临床高分辨率成像、实验室分析和骨活检研究，对allo-HSCT前后的骨髓纤维化患者进行了深入的骨骼特征分析。尽管外周骨骼部位的骨微结构未受损，但我们观察到腰椎和股骨近端的骨矿物质密度显著增加，这在组织学上与严重的骨髓纤维化和骨硬化有关，allo-HSCT后完全恢复正常。重要的是，纤维化的消退伴随着骨硬化的消失，同时破骨细胞吸收活性和全身钙稳态得以恢复。总之，我们的结果为allo-HSCT在骨髓纤维化中广泛重建骨骼稳态提供了证据，从而导致骨硬化的快速消退。
