TOPLINE:

Elexacaftor-tezacaftor-ivacaftor (ETI) therapy showed minimal impact on bone health in patients with cystic fibrosis over 3 years, with bone mineral density (BMD), Z scores, and calcium metabolism remaining largely stable across skeletal sites.

METHODOLOGY:

• Researchers conducted a real-world study using data from a Danish registry, analyzing 197 patients with cystic fibrosis (median age at therapy initiation, 30 years; 46% women) to assess changes in bone health after starting ETI therapy.
• All patients underwent annual DEXA during routine visits to measure BMD, Z scores, and T scores for the lumbar spine (L1-L4), total hip, and femoral neck at 2 years before ETI (pre-ETI) and the first year (≥ 6-18 months), second year (> 18-30 months), and third year (> 30-42 months) post treatment.
• The outcomes included changes in Z scores for the lumbar spine, total hip, and femoral neck and changes in plasma levels of vitamin D, calcium, and parathyroid hormone.

TAKEAWAY:

• The mean change in Z scores for the lumbar spine and total hip remained relatively stable over 3 years, whereas that for the femoral neck significantly decreased at years 1 and 3 compared with pre-ETI levels (P < .05 for both).
• Vitamin D levels initially decreased by a mean of 3.3 nmol/L (P = .04) at year 1 and then increased to a mean of 71.5 nmol/L (P < .01) at year 2 and a mean of 70.9 nmol/L (P < .01) at year 3 compared with the mean pre-ETI level of 62.0 nmol/L.
• Calcium levels decreased by a mean of 0.01 mmol/L (P < .01) during the first year and remained stable at a mean of 1.26 mmol/L thereafter, whereas parathyroid hormone levels remained stable throughout, with no significant changes.
• Absolute BMD and T scores were overall stable across all skeletal sites throughout the study period, with statistically significant changes emerging only at year 3 (mean change, 0.02; P < .05).

IN PRACTICE:

“Our findings highlight the need for further investigation into ETI’s role in bone health among pwCF [people with cystic fibrosis] and the need for ongoing attention to CFBD [cystic fibrosis bone disease] in an aging CF [cystic fibrosis] population, particularly as more women with CF reach menopause with suboptimal BMD in the future,” the authors of the study wrote.

SOURCE:

This study was led by Esben Herborg Henriksen, Cystic Fibrosis Center Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark. It was published online on February 18, 2026, in the Journal of Cystic Fibrosis.

LIMITATIONS:

This study had limited data granularity in the third posttreatment year and lacked high-resolution microarchitectural data, trabecular bone score, and information on bone turnover markers. Detailed data on changes in medication (eg, glucocorticoid use) that could have influenced bone outcomes were lacking. As a real-world registry study, it was vulnerable to confounding by indication. Finally, DEXA provides data on areal BMD only and does not capture information about bone quality or turnover.

DISCLOSURES:

This study was funded by Vertex Pharmaceuticals. The authors declared having no competing interests.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.