•> 50% of patients awaiting lung transplantation (LTx) have fragility fractures (Fx).•After LTx, BMD worsen in absence of bone-active therapy while improves in presence.•BMD changes are similar in patients with (CF) and without cystic fibrosis (nCF).•Fx incidence after LTx is higher in nCF patients than in CF ones.•After LTx TBS worsen in nCF patients, while it improves in CF patients. the effect of bone-active drugs on the risk of fragility fractures (Fx), bone mineral density (BMD) and trabecular bone score (TBS) changes in patients receiving lung transplantation (LTx) is largely unknown. This study assessed the bone-active drugs effect in patients undergoing LTx both with (CF) and without (nCF) cystic-fibrosis. We evaluated incident Fx, both clinical and morphometric vertebral Fx by spinal X-ray, BMD and trabecular bone score (TBS) in 117 patients (CF=50, nCF n = 67) before and 24-months after LTx. A bone-active therapy was proposed to all LTx candidates. 83.8% of patients started a bone-active drug. Lumbar-spine (LS) T-score improved significantly only in treated patients (-1.4 ± 1.0 vs -2.0±1.0, p = 0.0001), whereas femur BMD and TBS remained stable in treated and not treated subjects. The rate of incident Fx was 15.3%, with no difference between treated and not treated patients. After LTx, LS T-score improved significantly only in nCF group (-1.3 ± 1.0 vs -1.8 ± 1.1, p = 0.0001), while femur remained stable in both nCF and CF groups. Patients with CF showed a significant Z-TBS increase (-3.6 ± 1.7 vs -3.0 ± 1.7, p = 0.019) and a lower Fx incidence as compared with nCF patients (4.1% vs 24.2%, p  =0.003). Incident Fx were associated with nCF diagnosis (OR 7.300, CI95% 1.385–38.461, p = 0.019) regardless of prevalent Fx, previous glucocorticoid therapy and bone-active therapy introduced at least 6 months before LTx. A prompt medical intervention helps in preventing BMD loss after LTx. As compared with nCF patients, CF patients show a TBS increase and a lower Fx risk after LTx.