Longitudinal changes in bone mineral density among adults with cystic fibrosis: a systematic review and meta-analysis

Improved survival in cystic fibrosis (CF) has increased the burden of cystic fibrosis-related bone disease (CFBD), yet the natural history of bone mineral density (BMD) decline remains poorly defined. We conducted a systematic review and meta-analysis (PROSPERO: CRD420251091118) to quantify longitudinal BMD changes in adults with CF.

MEDLINE, Embase, Cochrane, and PubMed were searched through March 22, 2025 for observational studies and control arms of randomized trials reporting ≥2 dual-energy X-ray absorptiometry (DXA) scans ≥1 year apart in adults not receiving osteoporosis therapy; post-lung transplant DXAs were excluded. The primary outcome was annual percent change in BMD at the lumbar spine (LS) and femoral neck (FN). Random-effects models were used; heterogeneity was assessed with I².

Twelve studies (n = 811; mean age 21-31 years; mean follow-up 24 months) were included, with 10 contributing to meta-analysis. Pooled annual BMD change was -0.28%/year (95% CI: -0.56, -0.01) at the LS and -0.90%/year (95% CI: -1.29, -0.52) at the FN. Heterogeneity was low to moderate (I² = 28.7% LS; 44.5% FN). Methodological quality was generally high, though confounding and incomplete follow-up were common. All studies predated widespread CFTR modulator use.

Adults with CF experience progressive BMD loss, particularly at the FN, where the observed rate exceeded that expected for age. These findings support enhanced bone health strategies and highlight the need to evaluate CFTR modulator effects, fracture risk, and optimal monitoring in the modern treatment era.