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.

Background: Childhood cancer survivors (CCS) who receive a hematopoietic cell transplantation (HCT) are at increased risk for follicle-stimulating hormone (FSH) and luteinizing hormone (LH) abnormalities, which may have a substantial negative impact on vascular function. This study’s purpose was to examine the association of vascular function with FSH and LH in HCT recipients, non-HCT recipients and healthy controls. Procedures: The study included CCS who were HCT recipients (n=24) and non-HCT recipients (n=308), and a control group of healthy siblings (n=211) all aged between 9-18 years. Vascular measures of carotid artery structure and function (compliance and distensibility), brachial artery flow-mediated dilation (FMD) and nitroglycerin-mediated endothelial-independent dilation (EID) were measured using ultrasound imaging. FSH, LH, testosterone (males only), and estrogen (females only) were measured from a fasting blood sample. Results: FSH was significantly higher in HCT recipients compared to non-HCT recipients and healthy controls (p<0.01). The groups did not differ significantly for LH, testosterone, or estrogen. Carotid compliance and distensibility were significantly lower in HCT and non-HCT recipients compared to healthy controls (p<0.05). FMD and EID did not differ significantly between groups. Higher FSH was associated with decreased carotid compliance (p<0.05). Higher testosterone was associated with lower EID (p<0.05). Conclusion: This study’s results suggest that higher levels of FSH in HCT recipients may result in significant reductions in vascular function compared to non-HCT recipients and healthy controls. Therefore, endocrine dysfunction, particularly abnormal FSH levels, may be an underlying mechanism of vascular dysfunction.