Chapter 18 - Transplantation for Cystic Fibrosis: Effect on the Skeleton

Abstract

Cystic fibrosis (CF) occurs because of a mutation in the CF transmembrane conductance regulator (CFTR) protein, which is a chloride channel found in epithelial tissues in the lungs, pancreas, gastrointestinal tract, and skin. CFTR modulates the transport of salt and water across these epithelia. Mutations in CFTR lead to changes in the viscosity and hydration of epithelial tissue lining fluid leading to alterations in host defense in the respiratory tract and ultimately resulting in respiratory failure early in life. The origin of the bone disease in CF is poorly understood and probably multifactorial. Important contributing factors include malnutrition and poor growth, pancreatic insufficiency, vitamin D insufficiency, deficiency of sex hormones, inflammatory cytokines, and glucocorticoids therapy. Chronic pulmonary inflammation increases serum cytokine levels, which probably augment bone resorption and suppress bone formation. Decreased bone mineral density (BMD) resulting from these factors can lead to pathological fractures and kyphosis decades earlier than seen in the general population. The multifaceted nature of bone disease in CF makes it a particularly difficult problem to manage. Prevention, early recognition, and treatment are the most effective strategies for sustaining bone health to help maintain the quality of life of many CF patients.