TY - JOUR
T1 - Bone tissue homeostasis and risk of fractures in Costello syndrome: a four-year follow-up study
AU - Leoni, Chiara
AU - Viscogliosi, Germana
AU - Onesimo, Roberta
AU - Massese, Miriam
AU - Giorgio, Valentina
AU - Corbo, Fabio
AU - Cipolla, Clelia
AU - Rigante, Donato
AU - Zampino, Giuseppe
PY - 2022
Y1 - 2022
N2 - Costello syndrome (CS) is a neurodevelopmental disorder with a distinctive musculo-skeletal phenotype and reduced bone mineral density (BMD) caused by activating denovo mutations in theHRASgene. Herein, we report the results of a prospectivestudy evaluating the efficacy of a 4-year vitamin D supplementation on BMD andbone health. A cohort of 16 individuals ranging from pediatric to adult age withmolecularly confirmed CS underwent dosages of bone metabolism biomarkers(serum/urine) and dual-energy X-ray absorptiometry (DXA) scans to assess bone andbody composition parameters. Results were compared to age-matched controlgroups. At baseline evaluation, BMD was significantly reduced (p≤0.05) comparedto controls, as were the 25(OH)vitD levels. Following the 4-year time interval, despitevitamin D supplementation therapy at adequate dosages, no significant improvementin BMD was observed. The present data confirm that 25(OH)vitD and BMD parame-ters are reduced in CS, and vitamin D supplementation is not sufficient to restoreproper BMD values. Based on this evidence, routine monitoring of bone homeostasisto prevent bone deterioration and possible fractures in adult patients with CS ishighly recommended
AB - Costello syndrome (CS) is a neurodevelopmental disorder with a distinctive musculo-skeletal phenotype and reduced bone mineral density (BMD) caused by activating denovo mutations in theHRASgene. Herein, we report the results of a prospectivestudy evaluating the efficacy of a 4-year vitamin D supplementation on BMD andbone health. A cohort of 16 individuals ranging from pediatric to adult age withmolecularly confirmed CS underwent dosages of bone metabolism biomarkers(serum/urine) and dual-energy X-ray absorptiometry (DXA) scans to assess bone andbody composition parameters. Results were compared to age-matched controlgroups. At baseline evaluation, BMD was significantly reduced (p≤0.05) comparedto controls, as were the 25(OH)vitD levels. Following the 4-year time interval, despitevitamin D supplementation therapy at adequate dosages, no significant improvementin BMD was observed. The present data confirm that 25(OH)vitD and BMD parame-ters are reduced in CS, and vitamin D supplementation is not sufficient to restoreproper BMD values. Based on this evidence, routine monitoring of bone homeostasisto prevent bone deterioration and possible fractures in adult patients with CS ishighly recommended
KW - Costello syndrome
KW - Costello syndrome
UR - http://hdl.handle.net/10807/193502
U2 - 10.1002/ajmg.a.62615
DO - 10.1002/ajmg.a.62615
M3 - Article
SN - 1552-4825
VL - 188
SP - 422
EP - 430
JO - American Journal of Medical Genetics, Part A
JF - American Journal of Medical Genetics, Part A
ER -