Reduced bone density in cystic fibrosis: ΔF508 mutation is an independent risk factor

Abstract

The aim of this cross-sectional study was to determine the prevalence and identify determinants of reduced bone mineral density (BMD) in adults with cystic fibrosis (CF).Adults (88) with CF (mean¡SD age 29.9¡7.7 yrs; forced expiratory volume in one second (FEV1) 58.2¡21.5% of the predicted value) were studied. BMD at the lumbar spine (LS) and femoral neck (FN) and body composition were measured using dual-energy X-ray absorptiometry. Blood and urine were analysed for hormones, bone turnover markers, and the cytokines tumour necrosis factor-a, and interleukin-6 and -1b. FEV1 (% pred); CF genotype; malnutrition; history of growth, development or weight gain delays; and corticosteroid use were analysed.BMD Z-scores were -0.58¡1.30 (mean¡SD) at the LS and -0.24¡1.19 at the FN. Z-scores of ,-2.0 were found in 17% of subjects. Subjects who were homozygous or heterozygous for the DF508 mutation exhibited significantly lower Z-scores than those with no DF508 allele. Multiple linear regression showed that the DF508 genotype and male sex were independently associated with lower BMD at both sites. Other factors also independently associated with lower BMD included malnutrition, lower 25-hydroxyvitamin D level, lower fat-free mass and lower FEV1 (% pred).In conclusion, reduced bone mineral density in cystic fibrosis is associated with a number of factors, including DF508 genotype, male sex, greater lung disease severity and malnutrition.

Lactose malabsorption is a risk factor for decreased bone mineral density in pancreatic insufficient cystic fibrosis patients

“…However, they were predominantly young adolescents (median age of 13.6 years). King et al 25 did not observe a relationship between age and BMD, which should awaken a state of reflection, given that their studied group consisted of adults aged 19-59. In light of other clinical studies, the annualized rate of BMD loss in CF patients approaches to those seen in postmenopausal women.…”

“…26,27 Certainly, the monitoring of bone health and the starting of early intervention in CF patients is crucial owing to the poor bone status at a young age, which deteriorates as the patient ages. 5 Interestingly, King et al 25 have shown that the presence of the delF508 mutation is an independent risk factor of reduced BMD. We did not confirm this observation (logistic regression; P ¼ 0.732 and 0.815, respectively).…”

“…To some extent, this does seem to be justified, because BMD reflects bone health over the lifetime of the patient, and current vitamin D concentrations may fluctuate from season to season. 1,25 On the other hand, both parameters are simply related to LM. Nonetheless, the use of logistic regression for analysis of the study results has shown the strong relationship of BMD with both body weight (Po0.025) and LM (Po0.044).…”

Cystic Fibrosis Chronic Rhinosinusitis: A Comprehensive Review

“…For example, the most common mutation F508del homozygosity does not predict disease severity on its own, but this genotype is shown to be an independent risk factor in other manifestations of CF, including reduced mineral bone density and earlier colonization with Pseudomonas aeruginosa. 16,17 The diagnosis of classic CF is made when patients exhibit at least one characteristic phenotypic feature, have a family history of CF, or have a positive neonatal screening test. In addition to these requisites, the patients must also have positive testing with either an increased sweat chloride concentration (Ͼ60 mmol/L), genetic tests showing two CF causing mutations, or demonstration of an abnormal ancillary test indicative of CFTR abnormality (e.g., nasal epithelial ion transport or intestinal current measurement).…”

Cystic fibrosis and bone disease: are we missing a genetic link?

“…The manuscript by KING et al [1] in this issue of the European Respiratory Journal raises the possibility that mutations in the cystic fibrosis (CF) transmembrane conductance regulator (CFTR) may be responsible, at least in part, for low bone density in CF cohorts. More than 100 publications from around the globe, the majority in the last decade, have described low bone density in CF adult and, to a lesser extent, paediatric populations.…”