Oxytocin Effects on Bone Metabolism in Children with Autism Spectrum Disorder
Abstract
Autism spectrum disorders (ASD) are increasingly prevalent disorders affecting 1 in 44 American children. Children with ASD have lower bone mineral density (BMD), lower cortical and trabecular bone integrity, and a higher risk for hip fracture than controls. Potential factors causing bone loss in children with ASD include increased cortisol secretion, low levels of physical activity, and restricted diets and medication use, factors that are not easily modifiable. Since childhood and adolescence are a critical time for bone accrual towards attainment of peak bone mass, it is crucial to determine therapeutic strategies to optimize BMD during childhood in these children. Oxytocin (OXT), a hormone produced in the hypothalamus in the brain, is an important mediator of bone turnover, promoting bone formation over bone loss, based on preclinical studies. In addition to direct effects on bone, OXT may indirectly improve bone health by reducing the stress response, leading to lower cortisol levels. Finally, OXT increases muscle mass in rodents and humans, and lean mass is a critical determinant of bone health. Thus far, intranasal OXT has not yet been investigated as a therapeutic strategy to optimize bone mass acquisition. We propose a randomized, placebo-controlled investigation of intranasal OXT for bone health in children with ASD by studying in parallel the longitudinal effects of OXT vs. placebo on bone turnover markers, BMD, bone structure, and estimated bone strength. We hypothesize that, in children with ASD receiving OXT, bone density, structure, and strength estimates will improve over time. Further, OXT will result in an increase in bone formation and a decrease in bone loss (as indicated by surrogate bone turnover markers), consequent to both direct OXT effects and through reductions in cortisol and increases in lean mass (assessed by DXA and high resolution peripheral quantitative computed tomography HRpQCT). In this innovative proposal we will use cutting-edge tools (HRpQCT and microfinite element analysis) to determine changes in not only BMD, but also bone structure and estimated bone strength in children with ASD randomized to OXT vs. placebo, and mechanisms that may mediate the impact of OXT on bone turnover. This study will be the first to systematically investigate the efficacy and safety of OXT as a novel therapeutic agent to improve bone outcomes in children and adolescents with ASD. The potential impact of this trial is an increase in bone accrual and bone density in children with ASD with improved bone structure, increased bone strength and a reduction in fracture risk, both immediate and also long-term, given the expected impact on peak bone mass, a key determinant of future bone health.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 04, 2024
- Source ID
- HT94252310219
Entities
People
- Madhusmita Misra
Organizations
- Massachusetts General Hospital
- United States Army