Delgado-Calle, JesusAnderson, JudithCregor, Meloney D.Condon, Keith W.Kuhstoss, Stuart A.Plotkin, Lilian I.Bellido, TeresitaRoodman, G. David2018-05-032018-05-032017-12Delgado-Calle, J., Anderson, J., Cregor, M. D., Condon, K. W., Kuhstoss, S. A., Plotkin, L. I., … Roodman, G. D. (2017). Genetic Deletion of Sost or Pharmacological Inhibition of Sclerostin Prevent Multiple Myeloma-induced Bone Disease without Affecting Tumor Growth. Leukemia, 31(12), 2686–2694. https://doi.org/10.1038/leu.2017.1520887-6924https://hdl.handle.net/1805/16053Multiple myeloma (MM) causes lytic bone lesions due to increased bone resorption and concomitant marked suppression of bone formation. Sclerostin (Scl) levels, an osteocyte-derived inhibitor of Wnt/β-catenin signaling, are elevated in MM patient sera and are increased in osteocytes in MM-bearing mice. We show here that genetic deletion of Sost, the gene encoding Scl, prevented MM-induced bone disease in an immune-deficient mouse model of early MM, and that administration of anti-Scl antibody (Scl-Ab) increased bone mass and decreases osteolysis in immune-competent mice with established MM. Sost/Scl inhibition increased osteoblast numbers, stimulated new bone formation and decreased osteoclast number in MM-colonized bone. Further, Sost/Scl inhibition did not affect tumor growth in vivo or anti-myeloma drug efficacy in vitro. These results identify the osteocyte as a major contributor to the deleterious effects of MM in bone and osteocyte-derived Scl as a promising target for the treatment of established MM-induced bone disease. Further, Scl did not interfere with efficacy of chemotherapy for MM suggesting that combined treatment with anti-myeloma drugs and Scl-Ab should effectively control MM growth and bone disease, providing new avenues to effectively control MM and bone disease in patients with active MM.en-USPublisher PolicyGeneticsSost/Scl inhibitionMultiple myelomaArticle