TY - JOUR

T1 - Fibrous dysplasia animal models

T2 - A systematic review

AU - Hopkins, Chelsea

AU - de Castro, Luis Fernandez

AU - Corsi, Alessandro

AU - Boyce, Alison

AU - Collins, Michael T.

AU - Riminucci, Mara

AU - Heegaard, Anne Marie

N1 - Publisher Copyright: © 2021 The Authors

PY - 2022

Y1 - 2022

N2 - Background: Fibrous dysplasia (FD) is a rare genetic bone disorder resulting in an overproduction of cAMP leading to a structurally unsound tissue, caused by a genetic mutation in the guanine nucleotide-binding protein gene (GNAS). In order to better understand this disease, several animal models have been developed with different strategies and features. Objective: Conduct a systematic review to analyze and compare animal models with the causative mutation and features of FD. Methods: A PRISMA search was conducted in Scopus, PubMed, and Web of Science. Studies reporting an in vivo model of FD that expressed the causative mutation were included for analysis. Models without the causative mutation, but developed an FD phenotype and models of FD cell implantation were included for subanalysis. Results: Seven unique models were identified. The models were assessed and compared for their face validity, construct validity, mosaicism, and induction methods. This was based on the features of clinical FD that were reported within the categories of: macroscopic features, imaging, histology and histomorphometry, histochemical and cellular markers, and blood/urine markers. Limitations: None of the models reported all features of FD and some features were only reported in one model. This made comparing models a challenge, but indicates areas where further research is necessary. Conclusion: The benefits and disadvantages of every model were assessed from a practical and scientific standpoint. While all published reports lacked complete data, the models have nonetheless informed our understanding of FD and provided meaningful information to guide researchers in bench and clinical research.

AB - Background: Fibrous dysplasia (FD) is a rare genetic bone disorder resulting in an overproduction of cAMP leading to a structurally unsound tissue, caused by a genetic mutation in the guanine nucleotide-binding protein gene (GNAS). In order to better understand this disease, several animal models have been developed with different strategies and features. Objective: Conduct a systematic review to analyze and compare animal models with the causative mutation and features of FD. Methods: A PRISMA search was conducted in Scopus, PubMed, and Web of Science. Studies reporting an in vivo model of FD that expressed the causative mutation were included for analysis. Models without the causative mutation, but developed an FD phenotype and models of FD cell implantation were included for subanalysis. Results: Seven unique models were identified. The models were assessed and compared for their face validity, construct validity, mosaicism, and induction methods. This was based on the features of clinical FD that were reported within the categories of: macroscopic features, imaging, histology and histomorphometry, histochemical and cellular markers, and blood/urine markers. Limitations: None of the models reported all features of FD and some features were only reported in one model. This made comparing models a challenge, but indicates areas where further research is necessary. Conclusion: The benefits and disadvantages of every model were assessed from a practical and scientific standpoint. While all published reports lacked complete data, the models have nonetheless informed our understanding of FD and provided meaningful information to guide researchers in bench and clinical research.

KW - Animal

KW - Fibrous dysplasia

KW - In vivo

U2 - 10.1016/j.bone.2021.116270

DO - 10.1016/j.bone.2021.116270

M3 - Review

C2 - 34875396

AN - SCOPUS:85121460097

VL - 155

JO - Bone

JF - Bone

SN - 8756-3282

M1 - 116270

ER -