Genetics implicates overactive osteogenesis in the development of diffuse idiopathic skeletal hyperostosis

Area of Science:

• Genetics
• Osteology
• Medical Imaging

Background:

• Diffuse idiopathic skeletal hyperostosis (DISH) involves vertebral fusion via osteophytes.
• The genetic and epidemiological causes of DISH remain unclear.

Purpose of the Study:

• To assess DISH prevalence and severity using machine learning on DXA scans.
• To investigate the genetic and phenotypic associations of DISH.

Main Methods:

• Machine learning analysis of approximately 40,000 lateral DXA scans from the UK Biobank.
• Genetic association analysis to identify loci linked to DISH.

Main Results:

• DISH is highly prevalent in individuals over 45 (approx. 20% of men, 8% of women).
• A significant association was found between DISH, increased bone mineral density, and bone content.
• Ten genetic loci, including bone remodeling genes (RUNX2, IL11, GDF5, CCDC91, NOG, ROR2), were associated with DISH.

Conclusions:

• This study provides insights into the genetic underpinnings of DISH.
• Overactive osteogenesis appears to be a primary factor driving DISH pathology.