Abstract
Cystic fibrosis (CF) is a multisystemic genetic disorder caused by dysfunctional CF transmembrane conductance regulator (CFTR) protein, leading to impaired chloride and bicarbonate transport. Advances in care have increased patient lifetime, revealing chronic complications such as CF-related bone disease (CFBD), characterized by low bone mineral density and increased fracture risk. CFBD results from a complex interplay of factors including chronic inflammation, nutritional deficiencies, hormonal imbalances, and impaired glucose metabolism. Pro-inflammatory cytokines (e.g., TNF-α, IL-1β, IL-6, and IL-8) promote osteoclastogenesis, disrupting bone remodeling via the RANK/RANKL/OPG pathway. In vivo murine and in vitro studies have elucidated the pathogenic mechanisms underlying CFBD, highlighting CFTR's role in bone cell function. Diagnosis is based on clinical evaluation, bone densitometry, and laboratory assessments of bone metabolism markers. In this narrative review we highlight the recent scientific evidence on the etiopathogenesis and the current strategies for management of CFBD.