TY - JOUR
T1 - Predictors of low bone density and fracture risk in Loeys–Dietz syndrome
AU - Guerrerio, Anthony L.
AU - Mateja, Allyson
AU - Rasooly, Marjohn
AU - Levin, Samara
AU - Magnani, Alaina
AU - Dempsey, Caeden
AU - MacCarrick, Gretchen
AU - Dietz, Harry C.
AU - Brittain, Erica
AU - Boyce, Alison M.
AU - Frischmeyer-Guerrerio, Pamela A.
N1 - Publisher Copyright:
© 2021
PY - 2022/2
Y1 - 2022/2
N2 - 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.
AB - 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.
KW - Bone density
KW - DXA
KW - Fracture risk
KW - TGFβ
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U2 - 10.1016/j.gim.2021.10.002
DO - 10.1016/j.gim.2021.10.002
M3 - Article
C2 - 34906513
AN - SCOPUS:85122953446
SN - 1098-3600
VL - 24
SP - 419
EP - 429
JO - Genetics in Medicine
JF - Genetics in Medicine
IS - 2
ER -