Abstract

BackgroundDisuse is a cardinal sign of various neurological diseases like stroke, cerebral palsy, and amyotrophic lateral sclerosis. Disuse leads to reduced mechanical loading of the skeleton, and a substantial and significant loss of bone mass quickly materializes. Several animal models have been proposed to investigate the pathogenesis of disuse-induced bone loss and to test new pharmaceutical targets to counteract it. As animal models may overcome several of the limitations in observational studies conducted in patients and allow for measurements not possible in humans, the primary objective of the present study is to provide a comprehensive overview of the available animal models of disuse-induced bone loss.Methods/designThis is a protocol for a systematic review of animal models of disuse-induced bone loss. An exhaustive search will be performed on PubMed and Embase in order to identify relevant studies. The primary outcome will be the method of disuse induction. The secondary outcomes will be related to bone samples and anatomical sites investigated, methods used to analyze and quantify bone loss, and bibliographic information. The protocol adheres to the current guiding principles of the Preferred Reporting Items for Systematic Review and Meta-analysis Protocols (PRISMA-P) 2015 statement. Extracted data will be analyzed with descriptive statistics, and all the methods used to induce disuse will be described in detail with a narrative synthesis.DiscussionThis systematic review will provide an overview of available animal models of disuse-induced bone loss and discuss the different methods used to quantify and analyze the bone loss. Since bone loss caused by disuse is a hallmark of various diseases from different medical specialties, this overview will be of great benefit for all researchers planning to conduct disuse animal studies in the future.Systematic review registrationPROSPERO CRD42020157452.

Highlights

  • Disuse is a cardinal sign of various neurological diseases like stroke, cerebral palsy, and amyotrophic lateral sclerosis

  • This systematic review will provide an overview of available animal models of disuse-induced bone loss and discuss the different methods used to quantify and analyze the bone loss

  • Since bone loss caused by disuse is a hallmark of various diseases from different medical specialties, this overview will be of great benefit for all researchers planning to conduct disuse animal studies in the future

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Summary

Introduction

Disuse is a cardinal sign of various neurological diseases like stroke, cerebral palsy, and amyotrophic lateral sclerosis. Disuse leads to reduced mechanical loading of the skeleton, and a substantial and significant loss of bone mass quickly materializes. As animal models may overcome several of the limitations in observational studies conducted in patients and allow for measurements not possible in humans, the primary objective of the present study is to provide a comprehensive overview of the available animal models of disuse-induced bone loss. Animal models provide a unique opportunity to perform experiments under controlled conditions with a uniform population. It enables a framework for high reproducibility, allows to perform measurements not possible in humans, advances science by elucidating disease pathogenesis, and Inability to perform normal weight-bearing and locomotion quickly results in a loss of bone mass due to reduced mechanical stimulation. Disuse-induced bone loss is characterized by a reduced bone mineral density, deteriorated trabecular microarchitecture, and subsequent increased risk of complex fractures [5].

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