The effect of GIP and GLP-2 on bone turnover in children with Cerebral Palsy or Spinal Muscular Atrophy

Abstract Background Children with cerebral palsy (CP) and spinal muscular atrophy (SMA) are at high risk of low bone mineral density, fractures, and low muscle mass. The gut-derived hormones glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-2 (GLP-2) reduce bone resorption in adults, but their effects in paediatric populations with CP and SMA are unknown. Methods In this preliminary study, three children (1 CP, 2 SMA) underwent three interventions: (1) oral liquid mixed-meal ingestion, (2) subcutaneous GIP+GLP-2 administration, and (3) placebo. Plasma levels of GIP, GLP-2, CTX (bone resorption), P1NP (bone formation), and parathyroid hormone (PTH) were measured over 240 minutes. Results The liquid mixed-meal significantly reduced CTX levels, indicating suppressed bone resorption, while exogenous GIP+GLP-2 administration had no significant effect on CTX or P1NP. PTH levels decreased after GIP+GLP-2 administration but were unaffected by the liquid mixed-meal. Conclusion In these studies, exogenous GIP and GLP-2 unexpectedly did not modulate bone turnover in our children with CP or SMA. The study highlights the need for age- and disease-specific investigations into the gut–bone axis in paediatric populations.