Predictors of low bone density and fracture risk in Loeys–Dietz syndrome

Anthony L. Guerrerio, Allyson Mateja, Marjohn Rasooly, Samara Levin, Alaina Magnani, Caeden Dempsey, Gretchen MacCarrick, Harry C. Dietz, Erica Brittain, Alison M. Boyce, Pamela A. Frischmeyer-Guerrerio

Research output: Contribution to journalArticlepeer-review


Purpose: Loeys–Dietz syndrome (LDS) is a connective tissue disorder affecting multiple organ systems, including bone. Methods: We defined the bone phenotype and clinical predictors of low bone density and fracture risk in 77 patients with LDS type 1 to type 5. Results: Patients with LDS had dual-energy x-ray absorptiometry (DXA) Z-scores significantly < 0, and 50% of children and 9% of adults had Z-scores < –2. Sixty percent of patients had ≥1 fracture, and 24% of patients with spinal x-rays scans showed spinal compression fractures. Lower body mass index, asthma, male sex and eosinophilic gastrointestinal disease were correlated with lower DXA Z-scores. The count of 5 LDS-associated skeletal features (scoliosis, pes planus, arachnodactyly, spondylolisthesis, and camptodactyly) in patients with LDS was correlated with DXA Z-score. Adults with ≥1 skeletal features had DXA Z-scores significantly < 0, and children with >2 features had DXA Z-score significantly < –2. Bone turnover markers suggest accelerated bone resorption. Data from 5 patients treated with bisphosphonates suggest a beneficial effect. Conclusion: All LDS types are associated with reduced bone density and increased risk of fracture, which may be due to increased bone resorption. Clinical features can predict a subgroup of patients at highest risk of low bone density and fracture risk.

Original languageEnglish (US)
Pages (from-to)419-429
Number of pages11
JournalGenetics in Medicine
Issue number2
StatePublished - Feb 2022


  • Bone density
  • DXA
  • Fracture risk
  • TGFβ

ASJC Scopus subject areas

  • Genetics(clinical)


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