Bone tissue homeostasis and risk of fractures in Costello syndrome: a four-year follow-up study

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