Introduction: It is acknowledged that highly effective modulator treatment (HEMT), such as elexacaftor/tezacaftor/ivacaftor (ETI), can importantly improve quality of life of treatment eligible people with cystic fibrosis (pwCF). However, the effect of HEMT on bone mineral density (BMD) is unknown. The aim of our prospective study was to assess the effectiveness of ETI on BMD in treatment eligible children and young adults with CF.

Methods: Lumbar spine (LS) and whole-body (WB) BMD measured by dual energy X-ray absorptiometry was assessed before and following ETI commencement in pwCF older than 12 years in our CF centre. A multiple linear regression was calculated to assess potential predictors of BMD Z-score change.

Results: We collected BMD measurements of 17 patients (mean age 19.4 years, SD 2.9 years; 47.1% boys; 88.2% homozygous and 11.8% heterozygous for ?F508 mutation). Patients were receiving ETI for an average of 1.0 year (SD 0.6) before the control BMD measurement. A median LS 0.1, IQR -0.3-0.3, and WB 0.6, IQR 0.1-0.9 BMD z-score improvement was observed on ETI. Low WB BMD defined as Z-score less than -1 was identified in 52.2% pwCF before and 33.3% following treatment commencement (p=0.411). WB BMD z-score significantly improved on ETI (-1.3, SD 1.1 vs -0.8, SD 0.9, p=0.043). Change in lung function and nutrition did not influence BMD change in a multiple linear regression model.

Conclusions: The results of our study show improvement of BMD in pwCF receiving ETI. Moreover, it is suggested that the new therapeutic intervention could have a direct effect on BMD. Future larger studies are needed to better assess the effect of HEMT on BMD in pwCF.