@article{d87fd6672c7648a0b03003d1138cc518,
title = "Improving Bone Health by Optimizing the Anabolic Action of Wnt Inhibitor Multitargeting",
abstract = "Sclerostin antibody (romosozumab) was recently approved for clinical use in the United States to treat osteoporosis. We and others have explored Wnt-based combination therapy to disproportionately improve the anabolic effects of sclerostin inhibition, including cotreatment with sclerostin antibody (Scl-mAb) and Dkk1 antibody (Dkk1-mAb). To determine the optimal ratio of Scl-mAb and Dkk1-mAb for producing maximal anabolic action, the proportion of Scl-mAb and Dkk1-mAb were systematically varied while holding the total antibody dose constant. A 3:1 mixture of Scl-mAb to Dkk1-mAb produced two to three times as much cancellous bone mass as an equivalent dose of Scl-mAb alone. Further, a 75% reduction in the dose of the 3:1 mixture was equally efficacious to a full dose of Scl-mAb in the distal femur metaphysis. The Scl-mAb/Dkk1-mAb combination approach was highly efficacious in the cancellous bone mass, but the cortical compartment was much more subtly affected. The osteoanabolic effects of Wnt pathway targeting can be made more efficient if multiple antagonists are simultaneously targeted.",
keywords = "BONE ANABOLISM, OSTEOPOROSIS, SCLEROSTIN Dkk1, Wnt",
author = "Choi, {Roy B.} and Bullock, {Whitney A.} and Hoggatt, {April M.} and Loots, {Gabriela G.} and Genetos, {Damian C.} and Robling, {Alexander G.}",
note = "Funding Information: Financial support was provided by the NIH (AR053237 to AGR; AR073772 to DCG; DK075730 to GGL), the US Department of Veterans Affairs (BX001478 to AGR) and the US Department of Energy (DE-AC52-07NA27344 to GGL). Sclerostin and Dkk1 antibodies were provided by Amgen Inc. and UCB (Brussels, Belgium). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Authors' roles: RBC and AGR designed the experiments and wrote the paper. RBC collected and analyzed data. WAB and AMH contributed to mouse generation and assay design. GGL and DCG contributed to experimental design and data interpretation. AGR takes responsibility for the integrity of the data. Funding Information: Financial support was provided by the NIH (AR053237 to AGR; AR073772 to DCG; DK075730 to GGL), the US Department of Veterans Affairs (BX001478 to AGR) and the US Department of Energy (DE‐AC52‐07NA27344 to GGL). Sclerostin and Dkk1 antibodies were provided by Amgen Inc. and UCB (Brussels, Belgium). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Publisher Copyright: {\textcopyright} 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC. on behalf of American Society for Bone and Mineral Research.",
year = "2021",
month = may,
doi = "10.1002/jbm4.10462",
language = "English (US)",
volume = "5",
journal = "JBMR Plus",
issn = "2473-4039",
publisher = "Wiley-Blackwell Publishing Ltd",
number = "5",
}