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

The approval of cystic fibrosis transmembrane conductance regulator modulators elexacaftor/tezacaftor/ivacaftor (ETI), has significantly improved pulmonary function for people with cystic fibrosis (pwCF). However, the effects on CF-related bone disease and body composition remain unclear.

This retrospective real-world study examined adults with CF who received ETI treatment. Bone density and body composition were measured via dual-energy X-ray absorptiometry (DXA) 1.8 (SD 0.7) years before (preDXA) and 1.5 (SD 0.4) years after ETI initiation (postDXA1). In a subgroup, measurements were also available 4 (SD 0.6) years after initiation (postDXA2).

The study included 74 pwCF, of whom 42% were female, with an average age of 38.9 (SD 9.3) years at ETI initiation. Bone density decreased significantly at the spine (p = 0.02), left hip (p < 0.01), and right hip (p < 0.01) from pre- to postDXA1. No significant change in bone density was observed when comparing postDXA1 to postDXA2. Body composition analysis revealed significant increases in weight in both females (p < 0.01) and males (p < 0.01), as well as increases in fat mass in females (p < 0.01) and males (p < 0.01), without significant changes in lean mass (p = 0.4).

Bone density declined significantly during the study period, with the most pronounced decline occurring in the first 1.5 years after ETI initiation. However, this decline appeared to stabilize in participants with longer follow-up at 4 years post-ETI treatment, suggesting potential bone-protective effects with prolonged therapy. Body weight and fat mass increased early after ETI initiation, suggesting metabolic changes accompanying CFTR modulation.