Elexacaftor/Tezacaftor/Ivacaftor Effect on Bone Density and Body Composition: A Retrospective Analysis

Area of Science:

• Medical Research
• Pulmonology
• Endocrinology

Background:

• Cystic fibrosis transmembrane conductance regulator (CFTR) modulators like elexacaftor/tezacaftor/ivacaftor (ETI) have improved pulmonary function in people with CF (pwCF).
• The impact of ETI on CF-related bone disease and body composition remains under investigation.

Purpose of the Study:

• To evaluate the effects of ETI treatment on bone mineral density and body composition in adults with CF.
• To assess changes in bone density and body composition over time following ETI initiation.

Main Methods:

• Retrospective real-world study of 74 adults with CF receiving ETI.
• Dual-energy X-ray absorptiometry (DXA) measured bone density and body composition before ETI and at 1.5 and 4 years post-initiation.

Main Results:

• Bone density significantly decreased at the spine and hips from pre- to post-ETI initiation (1.5 years).
• No significant bone density changes were observed between 1.5 and 4 years post-ETI.
• Significant increases in weight and fat mass were observed in both males and females, with no change in lean mass.

Conclusions:

• Bone density declined early in ETI therapy but appeared to stabilize by 4 years, suggesting potential long-term bone benefits.
• Early increases in body weight and fat mass indicate metabolic adaptations to CFTR modulation.