Background
Most people living with Cystic fibrosis (CF) in Australia are now adults >18 years of age. With significant advancements in therapies including access to cystic fibrosis transmembrane (CFTR) modulator therapies, life expectancy continues to improve. CF is a monogenic disorder affecting the CFTR protein, which is present in bone. Adults with CF are known to have lower bone mineral density and are at risk of fragility fractures. However, the impacts of CFTR modulator therapies on bone health in adults with CF remains unclear. The objective of this study was to explore initial bone changes associated with the introduction of Elexacaftor-Tezacaftor-Ivacaftor (ETI) in adults attending a large CF centre.
Methods
Our CF centre uses a dedicated database to record clinical parameters for their entire patient cohort. We accessed the database to identify all adults with CF on ETI. Those with data available on change in hip or spine Z-scores on subsequent dual Xray absorptiometry (DEXA) performed before and at least 6-months after initiation of ETI were included in the study.
Results
We identified in total 7 (4 females) who met our inclusion criteria. Average vitamin D level was 72.6nmol/L. 3/7 (42%) also had concurrent CF-related diabetes. Most recent hip Z-scores ranged between -2.5 to +1.1 and spine Z-scores ranged between -1.9 to +2.9. We found improvement in hip Z-score in 2/7 (28%) and spine Z-scores in 1/7 (24%). The remainder of the group had deterioration in their Z-scores at both the hip and spine.
Discussion
Less than half of subjects demonstrated an increment in z-scores within 6 months of ETI commencement. Longer term and mechanistic studies will be required to determine whether through improved nutrition, reduced inflammation,, or direct effects on CFTR function within bone, ETI results in improved bone health.