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Current Analysis of Skeletal Phenotypes in Down Syndrome

  • Genetics (D Karasik and C Ackert-Bicknell, Section Editors)
  • Published:
Current Osteoporosis Reports Aims and scope Submit manuscript

Abstract

Purpose

Down syndrome (DS) is caused by trisomy 21 (Ts21) and results in skeletal deficits including shortened stature, low bone mineral density, and a predisposition to early onset osteoporosis. Ts21 causes significant alterations in skeletal development, morphology of the appendicular skeleton, bone homeostasis, age-related bone loss, and bone strength. However, the genetic or cellular origins of DS skeletal phenotypes remain unclear.

Recent Findings

New studies reveal a sexual dimorphism in characteristics and onset of skeletal deficits that differ between DS and typically developing individuals. Age-related bone loss occurs earlier in the DS as compared to general population.

Summary

Perturbations of DS skeletal quality arise from alterations in cellular and molecular pathways affected by the overexpression of trisomic genes. Sex-specific alterations occur in critical developmental pathways that disrupt bone accrual, remodeling, and homeostasis and are compounded by aging, resulting in increased risks for osteopenia, osteoporosis, and fracture in individuals with DS.

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Funding

Work on this publication was supported by the Eunice Kennedy Shriver National Institute of Child Health & Human Development of the National Institutes of Health under Award Number R15HD090603. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

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  1. Department of Biology, Indiana University-Purdue University Indianapolis, 723 West Michigan Street, SL 306, Indianapolis, IN, 46202-3275, USA

    Jared R. Thomas & Randall J. Roper

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Thomas, J.R., Roper, R.J. Current Analysis of Skeletal Phenotypes in Down Syndrome. Curr Osteoporos Rep 19, 338–346 (2021). https://doi.org/10.1007/s11914-021-00674-y

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