Inversed impaired osteogenic activity in children with severe obesity due to MC4R deficiency compared to leptin (LEP) and leptin receptor (LEPR) deficiency
Authors' conclusion
Our data demonstrate that osteogenic activity (but not resorption activity) is differentially affected in children with complete genetic disruption of the leptin-signaling pathway. Children with MC4R deficiency showed higher osteogenic markers, but children with LEP and LEPR deficiencies showed the opposite. Our results support the usefulness of bone turnover biomarkers for the assessment and management of bone health in different types of obesity.
Study context
- Population
- Children aged 0.3–8.8 years with BMI SDS ≥ 3 and pathogenic variants in LEP, LEPR or MC4R39 with LEP/LEPR/MC4R variants
- Exposure
- Children with LEP, LEPR or MC4R deficiency vs non-monogenic severe obesity vs normal-weight controls
- Severe obesity, variant-negativen = 13
- Controln = 13reference
- Outcome
- Bone formation markers (osteocalcin, osteopontin) and bone resorption markers
Methodological detailsage-matched controls
- Age-matched controls
Main finding
As reported in the abstract
- Serum osteocalcin and osteopontin significantly lower with LEP and LEPR biallelic variants than controls
- Osteocalcin and osteopontin significantly higher with MC4R deficiency than in the other groups
- No differences in bone resorption markers osteoprotegerin and sclerostin
Observational data: associations, not effects.
Further findings
Leptin, insulin and cortisol
- Hyperleptinemia more pronounced with LEPR deficiency
- Serum insulin elevated with MC4R deficiency
- Serum cortisol significantly higher with LEP deficiency than in all other groups
Original publication
Inversed impaired osteogenic activity in children with severe obesity due to MC4R deficiency compared to LEP and LEPR deficiency. Int J Obes (Lond). Published 13 March 2026. doi:10.
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