Background: Cystic fibrosis-related bone disease remains a significant cause of morbidity despite improvements in survival. Highly effective CFTR modulators, including elexacaftor/tezacaftor/ivacaftor (Trikafta), improve pulmonary function, nutritional status and quality of life. Whether these benefits translate into preservation of bone mineral density (BMD) remains uncertain.

Methods: We performed a retrospective cohort study of adults with cystic fibrosis treated with Trikafta at a tertiary referral centre. Patients with dual-energy X-ray absorptiometry (DEXA) scans performed before and after Trikafta initiation were included. Changes in BMD at the lumbar spine, total hip and femoral neck were analysed using paired comparisons. Secondary outcomes included changes in lung function (FEV₁% predicted) and body weight.

Results: 32 patients met inclusion criteria (mean age 36.1 years; 43% male). The median interval between DEXA scans was 4.15 years (IQR 3.48–5.08). Prior to Trikafta, 28% patients had low BMD at one or more skeletal sites, increasing to 34% at follow-up. There was no statistically significant improvement in BMD at the lumbar spine, total hip or femoral neck following Trikafta initiation (all p >0.05). Bone loss continued despite treatment, with 26% reduction in femoral neck BMD over the study period (approximately 6%/year), substantially exceeding the expected age-related decline. In contrast, Trikafta was associated with clinically meaningful improvements in respiratory and nutritional outcomes, with median FEV₁ increasing by 7% predicted and a median weight gain of 4 kg.

Conclusions: Despite significant improvements in lung function and nutritional status, Trikafta was not associated with preservation or improvement in bone mineral density in this cohort. These findings suggest that CF related bone disease may progress independently of pulmonary and nutritional recovery, highlighting the need for continued osteoporosis screening and optimisation of bone health in adults receiving highly effective CFTR modulators. Prospective longitudinal studies are required to better define the long-term skeletal effects of Trikafta.