Longitudinal changes in bone mineral density after initiation of elexacaftor-tezacaftor-ivacaftor in youth and adults with cystic fibrosis: PROMISE-ENDO.

BACKGROUND

Low bone mineral density (BMD) and increased fracture risk are common in individuals with cystic fibrosis (CF). The extent to which the CF transmembrane conductance regulator (CFTR) modulator elexacaftor-tezacaftor-ivacaftor (ETI) benefits BMD was a focus of the endocrine sub-study of PROMISE, a multicenter observational study of clinically prescribed ETI. We examined changes in whole-body (WB), lumbar spine (LS), total hip (TH), and femoral neck (FN) areal BMD (aBMD, g/cm2) in the 24-30 months (mos) following ETI initiation.

METHODS

Participants had CF, ≥1 F508del mutation, and were aged ≥12 years (y). Dual-energy X-ray absorptiometry (DXA) scans of the WB, LS, TH, and FN were collected before and following 12-18 mos and 24-30 mos of ETI therapy. Changes in aBMD Z-scores (aBMDZ) were examined with longitudinal mixed effects models.

RESULTS

Baseline aBMDZ was below-average at all skeletal sites in youth and adults (aBMDZ <0). Mixed model results for youth [n = 60 at baseline; average age 15y (range: 12-19.8); 48 % female] revealed decreases in WB (less head) (β-coefficient=-0.27; 95 %CI: -0.46, -0.09), LS (β=-0.26; 95 %CI: -0.42, -0.10), TH (β=-0.29; 95 %CI: -0.45, -0.13), and FN (β=-0.37; 95 %CI: -0.57, -0.17) aBMDZ between baseline and 12-18 mos. These changes persisted but did not worsen at 24-30 mos. Changes in adult [n = 73 at baseline; average age 28y (range: 20-58.8); 51 % female] aBMDZ were negative but modest compared to youth (no β-coefficient >-0.11).

CONCLUSIONS

Youth aBMDZ was lower at multiple skeletal sites 12-18 mos after ETI initiation, and these changes persisted at 24-30 mos. Adult aBMDZ generally remained unchanged.