Myeloproliferative Disorders and its Effect on Bone Homeostasis: The Role of Megakaryocytes

Abstract

Myeloproliferative Neoplasms (MPNs) are a heterogeneous group of chronic hematological diseases that arise from the clonal expansion of abnormal hematopoietic stem cells, of which Polycythemia Vera (PV), Essential Thrombocythemia (ET), and Primary Myelofibrosis (PMF) have been extensively reviewed in context of clonal expansion, fibrosis and other phenotypes. Here, we review current knowledge on the influence of different forms of MPN on bone health. Studies implicated various degrees of effect of different forms of MPN on bone density, and on osteoblast proliferation and differentiation, using murine models and human data. The majority of studies show that bone volume is generally increased in PMF patients, whereas it is slightly decreased or not altered in ET and PV patients, although possible differences between male and female phenotypes were not fully explored in most MPN forms. Osteosclerosis seen in PMF patients is a serious complication that can lead to bone marrow failure, and the loss of bone reported in some ET and PV patients can lead to osteoporotic fractures. Some MPN forms are associated with increased number of megakaryocytes (MKs), and several of the MK-associated factors in MPN are known to affect bone development. Here, we review known mechanisms involved in these processes, with focus on the role of MKs and secreted factors. Understanding MPN-associated changes in bone health could improve early intervention and treatment of this side effect of the pathology.