Skeletal Fragility in Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)

Author

Galen M. Goldscheitter, Virginia Commonwealth UniversityFollow

Author ORCID Identifier

0000-0002-6721-3161

Defense Date

2026

Document Type

Dissertation

Degree Name

Doctor of Philosophy

Department

Biomedical Engineering

First Advisor

Henry J. Donahue, PhD

Second Advisor

Barbara D. Boyan, PhD

Third Advisor

Damian C. Genetos, PhD

Fourth Advisor

Jennifer L. Puetzer, PhD

Fifth Advisor

Arun J. Sanyal, MD

Abstract

MASLD (Metabolic dysfunction-Associated Steatotic Liver Disease) is the most common chronic liver disease, affecting billions of people globally. People with MASLD experience more fractures than those without, which was only recently appreciated via large-scale epidemiologic studies. As such, no specific treatment exists for bone loss in MASLD. Further, the impact of MASLD-driving genetic variants on the skeleton are completely undefined. Bone loss in MASLD presents clinical and scientific knowledge gaps whose existence prevents the development and deployment of new interventions. Establishing relevant cellular, molecular, and genetic mechanisms is critical to address these gaps. It is possible to study the role of MASLD in bone loss in humans on a retrospective basis. Human studies also allow the study of bone loss in MASLD while also controlling for metabolic dysfunction, obesity, and type 2 diabetes mellitus as confounders. However, prospective studies are necessary to elucidate mechanisms of bone loss in MASLD and are nearly impossible in humans due to the massive sample populations required. However, a suitable animal model exists. The DIAMOND mouse (Diet Induced Animal Model of Non-alcoholic fatty liver Disease) develops MASLD following high-fat, high-carbohydrate diet exposure. The disease phenotype and environmental causes of MASLD in DIAMOND mice accurately mimic those of humans with MASLD. In this work, we describe putative molecular mechanisms of bone loss among mice with MASLD, define the risk of fracture among humans with MASLD, and describe the role of PNPLA3^I148M, a variant accounting for most MASLD heritability, in bone loss.

Rights

© Galen M Goldscheitter

Is Part Of

VCU University Archives

Is Part Of

VCU Theses and Dissertations

Date of Submission

2-13-2026