Adults with pathogenic MC4R mutations have increased final height and thereby increased bone mass

Area of Science:

• Endocrinology
• Bone Metabolism
• Obesity Research

Background:

• Pathogenic melanocortin-4 receptor (MC4R) mutations are linked to obesity and altered growth.
• Rodent studies suggest MC4R influences bone turnover.
• The impact of MC4R mutations on bone metabolism in adults remains unexamined.

Purpose of the Study:

• To assess the impact of MC4R on bone mass and metabolism in adults.
• To investigate the effect of the GLP-1 receptor agonist liraglutide on bone mass in adults with MC4R mutations.

Main Methods:

• 17 adults with MC4R mutations and 35 matched controls with common obesity underwent DEXA scans.
• Bone mineral density (BMD), bone mineral apparent density (BMAD), and bone turnover markers (BTMs) were assessed.
• Participants with BMI > 28 received 16 weeks of liraglutide (3.0 mg).

Main Results:

• MC4R mutation carriers exhibited higher BMD than controls (p=0.03).
• No significant differences in BMAD or BTMs were observed between groups.
• Liraglutide increased BMAD in controls (p=0.04) but not in MC4R mutation carriers.

Conclusions:

• Adults with MC4R-related obesity have higher BMD, but not size-adjusted bone mass, suggesting no MC4R influence on adult bone metabolism.
• Liraglutide did not alter bone metabolism in MC4R mutation carriers but increased size-adjusted bone mass in common obesity.