Cystic fibrosis-related bone disease

Abstract

Purpose of review This review will describe the clinical significance, pathogenesis and treatment of cystic fibrosis-related bone disease (CFBD). Recent findings CFBD continues to increase as the life expectancy of individuals with cystic fibrosis (CF) increases. According to clinical guidelines, individuals with CF should be initially screened at the age of 18 years via dual-energy x-ray absorptiometry (DXA), if not done so previously. The underlying pathogenesis of CFBD appears to be multifactorial, but increasing data imply a direct impact by the cystic fibrosis transmembrane conductance regulator (CFTR). CFTR deficiency and/or dysfunction impair osteoblast activity and differentiation, and indirectly promotes osteoclast formation. Unfortunately, once diagnosed with CFBD, few CF-tested medical therapies exist. Summary CFBD is an increasingly recognized complication that has a significant impact on the overall health of the individual. Recommendations to identify CF patients who are at risk for fracture using DXA have been established. Therapeutic agents directly studied in CF patients are limited to bisphosphonates, although other potential treatment agents exist. Finally, an improved understanding of the pathologic mechanisms will aid in the study and development of therapies.

Reduced bone length, growth plate thickness, bone content, and IGF-I as a model for poor growth in the CFTR-deficient rat

“…Osteopenia and osteoporosis combined—referred to as CF-related bone disease or CFBD—have a prevalence of 17% of all patients in the CF Foundation Patient Registry, and is a major impediment to quality of life and continued health of CF adolescents and young adults [ 1 ]. Bone health involves growth and formation, in childhood and adolescence, evolving into a continued dynamic interaction of bone reabsorption and new bone formation in adulthood [ 2 ]. Evidence, in both animal and human studies, supports a defect in CFBD stemming from both excessive bone resorption and decreased bone formation [ 2 ].…”

Streptomycin treatment alters the intestinal microbiome, pulmonary T cell profile and airway hyperresponsiveness in a cystic fibrosis mouse model

“…Specifically, the intestinal disease manifests in CF patients as meconium ileus or distal intestinal obstructive syndrome 7 , and features small intestinal bacterial overgrowth 8 and fecal microbial dysbiosis 9 10 11 12 13 . Bone disease, including fragile bones, reduced bone mineral density, osteoporosis 14 , and altered bone architecture 15 can also occur in some CF patients. CF bone disease may be related to vitamin D and K deficiencies, calcium malabsoption, chronic inflammation, hormone deficiencies and CFTR dysfunction 14 , while mucus buildup, increased transit time, decreased pH and antimicrobial deficiencies have been proposed to contibute to the CF intestinal disease 16 .…”

“…Bone disease, including fragile bones, reduced bone mineral density, osteoporosis 14 , and altered bone architecture 15 can also occur in some CF patients. CF bone disease may be related to vitamin D and K deficiencies, calcium malabsoption, chronic inflammation, hormone deficiencies and CFTR dysfunction 14 , while mucus buildup, increased transit time, decreased pH and antimicrobial deficiencies have been proposed to contibute to the CF intestinal disease 16 . However, the underlying mechanisms associated with these disease manifestions are unclear 14 16 .…”

Endocrine Disorders in Cystic Fibrosis

“…The causes of cystic fibrosis related bone disease are multi-factorial and include nutritional deficiencies of vitamin D, K and calcium, glucocorticoid use, sex steroid deficiency, an altered growth hormone axis, inflammation and the mutation of the CFTR gene itself 37 . The prevalence of fractures in children and adults with CF have been reported to occur in up to a third of patients 38, 39 .…”