Background The approval of cystic fibrosis conductance regulator (CFTR) modulators including the triple modulator Elexacaftor/Tezacaftor/Ivacaftor (ETI) for people with cystic fibrosis (pwCF) have improved pulmonary function significantly. The effect on CF related bone disease (CFBD) and body composition remain unclear. Methods This is a retrospective real world study of adults pwCF. Bone density and body composition were obtained via dual-energy x-ray absorptiometry (DXA) 1.8 (SD0.7) years prior and 1.5 (SD0.4) years (postDXA1) and in a subgroup 3.5 (SD0.2) years (postDXA2) after ETI initiation. Clinical data were collected at time of DXA scan and ETI start. Results 74 pwCF were included of which 42% were female, with average age at ETI initiation of 38.9 (SD 9.3) years. 45.9% had cystic fibrosis related diabetes (CFRD) and 93.2% had exocrine pancreatic insufficiency. Bone density decreased at the spine (p= 0.0256), left hip (p< 0.001) and right hip (p< 0.001) from pre- to postDXA1, no change in bone density was seen in any of the sites when postDXA1 was compared to postDXA2. Body composition in the postDXA1 compared to preDXA showed increase in weight in female (p=0.011) and male (p=0.001), and in fat mass in female (p=0.003) and male (p=0.001), without a change in lean mass (p=0.4). Comparison of body composition in postDXA2 to postDXA1 failed to show significant change in body weight (woman p=0.38; men p=0.94) and in fat mass (woman p=77; men p=0.939). Conclusions Bone density decreased and body weight and fat mass increased early on after ETI initiation. This appears to stabilize with prolonged treatment.