Sclerostin Depletion Induces Inflammation in the Bone Marrow of Mice

Romosozumab, a humanized monoclonal antibody specific for sclerostin (SOST), has been approved for treatment of postmenopausal women with osteoporosis at a high risk for fracture. Previous work in sclerostin global knockout () mice indicated alterations in immune cell development in the bone marrow (BM), which could be a possible side effect in romosozumab-treated patients. Here, we examined the effects of short-term sclerostin depletion in the BM on hematopoiesis in young mice receiving sclerostin antibody (Scl-Ab) treatment for 6 weeks, and the effects of long-term deficiency on wild-type (WT) long-term hematopoietic stem cells transplanted into older cohorts of mice. Our analyses revealed an increased frequency of granulocytes in the BM of Scl-Ab-treated mice and WT→ chimeras, indicating myeloid-biased differentiation in -deficient BM microenvironments. This myeloid bias extended to extramedullary hematopoiesis in the spleen and was correlated with an increase in inflammatory cytokines TNFα, IL-1α, and MCP-1 in BM serum. Additionally, we observed alterations in erythrocyte differentiation in the BM and spleen of mice. Taken together, our current study indicates novel roles for in the regulation of myelopoiesis and control of inflammation in the BM.