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World J Orthop. Sep 18, 2021; 12(9): 651-659
Published online Sep 18, 2021. doi: 10.5312/wjo.v12.i9.651
Effects of sclerostin antibody on bone healing
Atsushi Mihara, Kiminori Yukata, Toshihiro Seki, Ryuta Iwanaga, Norihiro Nishida, Kenzo Fujii, Yuji Nagao, Takashi Sakai
Atsushi Mihara, Kiminori Yukata, Toshihiro Seki, Ryuta Iwanaga, Norihiro Nishida, Kenzo Fujii, Yuji Nagao, Takashi Sakai, Department of Orthopedic Surgery, Yamaguchi University Graduate School of Medicine, Ube 755-8505, Japan
Author contributions: Mihara A and Yukata K performed the majority of the writing; Sakai T and Seki J designed the outline and coordinated the writing of the paper; Nishida N, Fujii K, Nagao Y, and Iwanaga R reviewed the manuscript.
Conflict-of-interest statement: The authors have no conflicts of interest.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Kiminori Yukata, MD, PhD, Associate Professor, Department of Orthopedic Surgery, Yamaguchi University Graduate School of Medicine, 1-1-1 Minami-Kogushi, Ube 755-8505, Japan. kyukata2004jp@yahoo.co.jp
Received: March 8, 2021
Peer-review started: March 8, 2021
First decision: March 31, 2021
Revised: April 12, 2021
Accepted: August 4, 2021
Article in press: August 4, 2021
Published online: September 18, 2021
Processing time: 190 Days and 0.1 Hours
Abstract

Promoting bone healing after a fracture has been a frequent subject of research. Recently, sclerostin antibody (Scl-Ab) has been introduced as a new anabolic agent for the treatment of osteoporosis. Scl-Ab activates the canonical Wnt (cWnt)-β-catenin pathway, leading to an increase in bone formation and decrease in bone resorption. Because of its rich osteogenic effects, preclinically, Scl-Ab has shown positive effects on bone healing in rodent models; researchers have reported an increase in bone mass, mechanical strength, histological bone formation, total mineralized callus volume, bone mineral density, neovascularization, proliferating cell nuclear antigen score, and bone morphogenic protein expression at the fracture site after Scl-Ab administration. In addition, in a rat critical-size femoral-defect model, the Scl-Ab-treated group demonstrated a higher bone healing rate. On the other hand, two clinical reports have researched Scl-Ab in bone healing and failed to show positive effects in the femur and tibia. This review discusses why Scl-Ab appears to be effective in animal models of fracture healing and not in clinical cases.

Keywords: Canonical Wnt-β-catenin pathway; Fracture healing; Osteoporosis; Romosozumab; Sclerostin antibody

Core Tip: Sclerostin antibody (Scl-Ab) has been recently introduced for the treatment of osteoporosis. Several researchers have reported on the effects of Scl-Ab in bone fracture healing because of its rich osteogenic potential. In this review, we describe the latest reports of preclinical and clinical studies on the bone-healing effects of Scl-Ab.