Antibodies to sclerostin or G-CSF receptor partially eliminate bone or marrow adipocyte loss, respectively, following vertical sleeve gastrectomy

Ziru Li, University of Michigan Medical School, Department of Molecular & Integrative Physiology, Ann Arbor, MI, United States of America; MaineHealth Institute for Research, Scarborough, ME, United States of America.
Kevin Qiu, University of Michigan Medical School, Department of Molecular & Integrative Physiology, Ann Arbor, MI, United States of America.
Jingtong Zhao, University of Michigan Medical School, Department of Molecular & Integrative Physiology, Ann Arbor, MI, United States of America.
Katrina Granger, University of Michigan Medical School, Department of Molecular & Integrative Physiology, Ann Arbor, MI, United States of America.
Hui Yu, University of Michigan Medical School, Department of Molecular & Integrative Physiology, Ann Arbor, MI, United States of America.
Alfor G. Lewis, University of Michigan Medical School, Department of Surgery, Ann Arbor, MI, United States of America.
Andriy Myronovych, University of Michigan Medical School, Department of Surgery, Ann Arbor, MI, United States of America.
Mouhamadoul H. Toure, University of Michigan Medical School, Department of Surgery, Ann Arbor, MI, United States of America.

Abstract

Vertical sleeve gastrectomy (VSG), the most utilized bariatric procedure in clinical practice, greatly reduces body weight and improves a variety of metabolic disorders. However, one of its long-term complications is bone loss and increased risk of fracture. Elevated circulating sclerostin (SOST) and granulocyte-colony stimulating factor (G-CSF) concentrations have been considered as potential contributors to VSG-associated bone loss. To test these possibilities, we administrated antibodies to SOST or G-CSF receptor and investigated alterations to bone and marrow niche following VSG. Neutralizing either SOST or G-CSF receptor did not alter beneficial effects of VSG on adiposity and hepatic steatosis, and anti-SOST treatment provided a further improvement to glucose tolerance. SOST antibodies partially reduced trabecular and cortical bone loss following VSG by increasing bone formation, whereas G-CSF receptor antibodies had no effects on bone mass. The expansion in myeloid cellularity and reductions in bone marrow adiposity seen with VSG were partially eliminated by treatment with Anti-G-CSF receptor. Taken together, these experiments demonstrate that antibodies to SOST or G-CSF receptor may act through independent mechanisms to partially block effects of VSG on bone loss or marrow niche cells, respectively.