Animal models of disuse-induced bone loss: study protocol for a systematic review

BACKGROUND: 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. 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/DESIGN: This 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. DISCUSSION: 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. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42020157452.