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

Anurag Sethi1, J Graham Ruby2, Matthew A Veras2

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Diffuse idiopathic skeletal hyperostosis (DISH) is common in adults over 45. This study reveals DISH is linked to higher bone density and identifies key genes involved in bone remodeling.

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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.