Bone health after 3 years of ETI therapy: a real-world study from the Danish cystic fibrosis cohort.

BACKGROUND

Malnutrition, inflammation, limited exercise, and low muscle mass increase the risk of cystic fibrosis (CF) bone disease (CFBD). Additionally, dysfunction of the CF transmembrane conductance regulator (CFTR) directly affects bone-forming cells. Elexacaftor/Tezacaftor/Ivacaftor (ETI) could influence these aspects. We examined the impact of ETI on bone health in Danish people with CF.

METHODS

This nationwide cohort study evaluated changes in bone status in adults with CF after ETI treatment. Dual energy X-ray absorptiometry (DXA) was used to assess bone mineral density Z-scores in lumbar spine, femoral neck, and total hip. To assess calcium metabolism, plasma levels of vitamin D, calcium, and parathyroid hormone (PTH) were evaluated. Data were collected from 2 years pre- to 3.5 years post-ETI initiation, comparing pre-ETI levels with 1-, 2- and 3-year post-ETI measurements. Data were analyzed using linear mixed effects regression models and subgroup interaction analyses.

RESULTS

197 Danish adults with CF were included in the study, contributing 435 DXA scans. Mean change from pre-ETI period (95%CI) in femoral neck and total hip Z-scores showed a decrease by year 3 of -0.16 (-0.31; -0.01; p=0.04) and -0.15 (-0.30; <0.01; p=0.05), respectively, while lumbar spine showed a slight increase of 0.13 (-0.05, 0.31; p=0.15). Vitamin D levels initially decreased but subsequently increased by 8.9 nmol/L (4.5-13.3; p<0.01) by year 3 as compared to pre-ETI levels. Calcium and PTH levels remained stable.

CONCLUSION

After 3 years of ETI treatment in Danish adults with CF, no clinically significant changes in bone health or calcium metabolism were observed.