@article{05eb86559ba14470bd532eb44872580e,
title = "Treatment with a long-acting chimeric CSF1 molecule enhances fracture healing of healthy and osteoporotic bones",
abstract = "Macrophage-targeted therapies, including macrophage colony-stimulating factor 1 (CSF1), have been shown to have pro-repair impacts post-fracture. Preclinical/clinical applications of CSF1 have been expedited by development of chimeric CSF1-Fc which has extended circulating half-life. Here, we used mouse models to investigate the bone regenerative potential of CSF1-Fc in healthy and osteoporotic fracture. We also explored whether combination of CSF1-Fc with interleukin (IL)-4 provided additional fracture healing benefit in osteopenic bone. Micro-computed tomography, in situ histomorphometry, and bone mechanical parameters were used to assess systemic impacts of CSF1-Fc therapy in naive mice (male and female young, adult and geriatric). An intermittent CSF1-Fc regimen was optimized to mitigate undesirable impacts on bone resorption and hepatosplenomegaly, irrespective of age or gender. The intermittent CSF1-Fc regimen was tested in a mid-diaphyseal femoral fracture model in healthy bones with treatment initiated 1-day post-fracture. Weekly CSF1-Fc did not impact osteoclasts but increased osteal macrophages and improved fracture strength. Importantly, this treatment regimen also improved fracture union and strength in an ovariectomy-model of delayed fracture repair. Combining CSF1-Fc with IL-4 initiated 1-week post-fracture reduced the efficacy of CSF1-Fc. This study describes a novel strategy to specifically achieve bone regenerative actions of CSF1-Fc that has the potential to alleviate fragility fracture morbidity and mortality.",
keywords = "Bone regeneration, Colony stimulating factor 1, Fracture repair, Osteal macrophages, Osteomacs, Osteoporotic fracture",
author = "Lena Batoon and Millard, {Susan M.} and Raggatt, {Liza J.} and Cheyenne Sandrock and Edmund Pickering and Kyle Williams and Sun, {Lucas W.H.} and Wu, {Andy C.} and Irvine, {Katharine M.} and Peter Pivonka and Vaida Glatt and Wullschleger, {Martin E.} and Hume, {David A.} and Pettit, {Allison R.}",
note = "Funding Information: This work was supported by Mater Foundation and a National Health and Medical Research Council Project Grant [APP1143802], The University of Queensland Postgraduate Scholarship and Mater Research Frank Clair Scholarship (LB) and an Australian Research Council Future Fellowship [ARP, FT150100335]. This work was carried out at the Translational Research Institute (TRI) which is supported by a grant from the Australian Government. The TRI Microscopy, Histology, Preclinical Imaging and Flow Cytometry Core Facilities contributed technical expertise and the TRI Biological Research Facility contributed to animal husbandry and monitoring. Melissa Johnston and the laboratory technical services of the Science and Engineering Faculty (QUT) assisted with mechanical testing. Funding Information: This work was supported by Mater Foundation and a National Health and Medical Research Council Project Grant [ APP1143802 ], The University of Queensland Postgraduate Scholarship and Mater Research Frank Clair Scholarship (LB) and an Australian Research Council Future Fellowship [ARP, FT150100335 ]. This work was carried out at the Translational Research Institute (TRI) which is supported by a grant from the Australian Government . The TRI Microscopy, Histology, Preclinical Imaging and Flow Cytometry Core Facilities contributed technical expertise and the TRI Biological Research Facility contributed to animal husbandry and monitoring. Melissa Johnston and the laboratory technical services of the Science and Engineering Faculty (QUT) assisted with mechanical testing. Publisher Copyright: {\textcopyright} 2021 Elsevier Ltd",
year = "2021",
month = aug,
doi = "10.1016/j.biomaterials.2021.120936",
language = "English (US)",
volume = "275",
journal = "Biomaterials",
issn = "0142-9612",
publisher = "Elsevier BV",
}