Updates in Cystic Fibrosis Bone Disease in Adults

To summarize current understanding of cystic fibrosis-related bone disease (CFBD), including its pathophysiology, epidemiology, screening recommendations and management in adults, and to highlight knowledge gaps and research priorities in the era of highly effective CFTR modulator therapy.

A narrative review of the existing literature on CFBD, encompassing the pathophysiology, epidemiologic data, clinical guidelines for screening and fracture risk assessment, and evidence supporting pharmacologic and non-pharmacologic treatments in adults with CFBD.

Cystic fibrosis (CF) is a multisystem autosomal recessive disease caused by variants of the cystic fibrosis transmembrane conductance regulator (CFTR) gene. As survival improves with modulator therapy, CFBD has become an increasingly prevalent complication. Its pathogenesis is multifactorial, due to intrinsic CFTR dysfunction in bone compounded by malnutrition, vitamin deficiencies, chronic inflammation, CF-related diabetes, hypogonadism, and exposure to high-risk medications. Up to two-thirds of adults over 45 years have low bone density, conferring a 2-10-fold higher fragility fracture risk. Current guidelines recommend routine dual-energy x-ray absorptiometry, vertebral fracture assessment, and laboratory evaluation, with individualized bone therapy. Nonpharmacologic therapy includes nutritional optimization, physical activity, and modification of risk factors. Pharmacologic management, including use of bisphosphonates, denosumab and anabolic agents, is extrapolated from general osteoporosis data.

CFBD is a significant and growing complication in adults with CF. Evidence gaps regarding long-term skeletal effects of CFTR modulators and optimal prevention and treatment strategies, underscores the need for prospective data to guide clinical practice.