Systematic Reviews
Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Orthop. Jul 18, 2020; 11(7): 328-344
Published online Jul 18, 2020. doi: 10.5312/wjo.v11.i7.328
Oxysterols as promising small molecules for bone tissue engineering: Systematic review
Ethan Cottrill, Julianna Lazzari, Zach Pennington, Jeff Ehresman, Andrew Schilling, Naomi Dirckx, Nicholas Theodore, Daniel Sciubba, Timothy Witham
Ethan Cottrill, Julianna Lazzari, Zach Pennington, Jeff Ehresman, Andrew Schilling, Naomi Dirckx, Nicholas Theodore, Daniel Sciubba, Timothy Witham, Department of Neurosurgery, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, United States
Author contributions: Cottrill E contributed to conception and design; acquisition, analysis, and interpretation of data; drafting the manuscript; and critical revision of the manuscript; Lazzari J and Pennington Z contributed to acquisition, analysis, and interpretation of data; drafting the manuscript; and critical revision of the manuscript. Ehresman J, Schilling A, Dirckx N, Theodore N, Sciubba D, and Witham T contributed to analysis and interpretation of data and critical revision of the manuscript; all authors reviewed and approved the final manuscript as submitted.
Conflict-of-interest statement: The authors declare no relevant conflicts of interest. Cottrill E receives non-study-related grant support from National Institute on Aging. Theodore N is a consultant for Globus and receives royalties from Globus and Depuy Synthes; Sciubba D is a consultant for Baxter, DePuy Synthes, Globus, K2M, Medtronic, NuVasive, and Stryker, and receives non-study-related grant support from Baxter, North American Spine Society, and Stryker. Witham T is a consultant for DePuy Synthes, is an advisory board member and shareholder of Augmedics, and receives non-study-related grant support from the Gordon and Marilyn Macklin Foundation.
PRISMA 2009 Checklist statement: PRISMA guidelines were followed for this systematic review.
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: Ethan Cottrill, MSc, Research Scientist, Department of Neurosurgery, The Johns Hopkins University School of Medicine, 600 North Wolfe Street, Baltimore, MD 21287, United States. ecottri1@jhmi.edu
Received: January 14, 2020
Peer-review started: January 14, 2020
First decision: April 22, 2020
Revised: May 8, 2020
Accepted: July 1, 2020
Article in press: July 1, 2020
Published online: July 18, 2020
Core Tip

Core tip: Here we present the first systematic review evaluating the utility of oxysterols for bone tissue engineering. Thirteen preclinical studies examining seven unique oxysterols were evaluated; all examined compounds were found to have statistically significant in vivo osteoinductive properties, with some showing dose-dependent effects. Importantly, eight studies found oxysterols to have similar osteoinductive properties to rhBMP-2 in treated animals. These effects are thought to occur through direct activation of Smoothened in the Hedgehog signaling pathway. Future clinical work is necessary to determine the exact therapeutic utility of these molecules in orthopaedic surgery patients.