MASH-induced elevation of FGF23 promotes hepatic osteodystrophy

Area of Science:

• Hepatology
• Bone Biology
• Endocrinology

Background:

• Metabolic dysfunction-associated steatohepatitis (MASH) is a progressive liver disease.
• MASH can lead to hepatic osteodystrophy, characterized by bone weakness and fractures.
• Current treatments like calcium supplementation are often ineffective for MASH-related bone issues.

Purpose of the Study:

• Investigate the role of fibroblast growth factor 23 (FGF23) in MASH-induced hepatic osteodystrophy.
• Determine the impact of elevated FGF23 on bone mineral density and remodeling in MASH.
• Explore the mechanisms by which FGF23 affects osteoblast and osteoclast activity.

Main Methods:

• Generated MASH mouse models using a choline- and methionine-deficient high-fat diet.
• Performed histological and biochemical analyses to assess liver steatosis and inflammation.
• Utilized micro-computed tomography to evaluate bone mineral density and structure.
• Measured serum FGF23 and phosphorus levels.
• Assessed the effects of FGF23 on osteoblast and osteoclast differentiation in vitro.

Main Results:

• MASH mice exhibited severe hepatic steatosis, inflammation, and weakened bones (decreased bone mineral density, trabecular number; increased trabecular separation).
• Serum FGF23 levels were significantly elevated in MASH mice, while serum phosphorus remained unchanged.
• FGF23 promoted osteoclast differentiation and suppressed osteoblast differentiation, indicating a role in bone remodeling imbalance.

Conclusions:

• Elevated FGF23 in MASH contributes to hepatic osteodystrophy by disrupting bone remodeling.
• FGF23 may be a key mediator linking MASH to bone disease.
• Targeting FGF23 could offer a novel therapeutic strategy for MASH-related bone complications.