Inflammatory related changes in bone mineral content in adults with cystic fibrosis

Abstract

Background: Proinflammatory cytokines stimulate osteoclast activity and this could lead to increased bone resorption in patients with cystic fibrosis. The aim of this study was to determine whether markers of systemic inflammation are related to changes in bone mineral content (BMC) in adults with cystic fibrosis. Methods: Total body BMC was assessed by dual energy x ray absorptiometry in 100 patients (54 male) of mean (SD) age 25.6 (7.1) years and forced expiratory volume in 1 second (FEV 1 ) 61.8 (24.1)% predicted on recruitment to the study and 1 year later. Blood was also taken at these time points to measure markers of systemic inflammation. Results: After 1 year BMC had reduced by 16.1 (62.1) g, p = 0.01; (0.6 (2.8)%). The change in BMC was related to mean levels of interleukin (IL)-6 (r s = 20.39, p,0.001) and C reactive protein (r s = 20.34, p = 0.002), intravenous antibiotic use (r s = 20.27, p = 0.006) and oral corticosteroid use (r s = 20.20, p = 0.045). Urinary markers of osteoclast activity were also related to IL-6 (r s = 0.27, p = 0.02). Multiple linear regression revealed that IL-6 (coefficient -2.2 (95% CI -3.4 to -1.0) per pg/ml, p = 0.001), colonisation with Burkholderia cepacia (coefficient -46.8 (95% CI -75.5 to -18.1), p = 0.002), and annual change in BMI (coefficient 15.4 (95% CI 3.6 to 27.2) per kg/m 2 , p = 0.011) were independently significant predictors of annual change in BMC. Conclusions: These data suggest a pathophysiological mechanism by which chronic pulmonary infection results in bone loss in patients with cystic fibrosis.

Relationship between insulin-like growth factor I, dehydroepiandrosterone sulfate and proresorptive cytokines and bone density in cystic fibrosis

“…However, in that group, no significant correlations were found between cytokine levels and bone density. Our present findings differ from those reported previously showing elevated cytokines in patients with CF [29][30][31][32][33][34]. One explanation is the use of inhaled glucocorticoids by all study participants in the current sample.…”

“…Previous studies have documented both low [34,[48][49][50] and normal [50,51] serum 25OHD concentrations in patients with CF. A prevalence of vitamin D deficiency of 38% seen among the current participants is the exact prevalence noted by Haworth et al [34], and participants in that study were also receiving vitamin D supplementation.…”

“…Previous studies have documented both low [34,[48][49][50] and normal [50,51] serum 25OHD concentrations in patients with CF. A prevalence of vitamin D deficiency of 38% seen among the current participants is the exact prevalence noted by Haworth et al [34], and participants in that study were also receiving vitamin D supplementation. While previous studies have shown that vitamin D status is a predictor of bone mass in these patients [12,47], our data replicate those of two previous studies [6,9] in showing that this variable was not predictive.…”

“…Two reports have shown that TNF-α production by lung macrophages was elevated in patients with CF [29,30], and other studies have shown elevations of serum TNF-α [31], IL-1β [30], and IL-6 [30,32,33] concentrations in these patients. Haworth et al [34] found an inverse correlation between skeletal losses and serum IL-6 concentrations over a 1-year period in a study of young adults with CF. In studies using both rodent [35] and human in vitro [36] models, DHEA supplementation led to decreased IL-6 concentrations, suggesting antiresorptive properties.…”

Alendronate Once Weekly for the Prevention and Treatment of Bone Loss in Canadian Adult Cystic Fibrosis Patients (CFOS Trial)

“…Another potential mechanism is that the chronic pulmonary inflammation associated with CF leads to elevated levels of circulating cytokines, which in turn promote bone resorption and suppress bone formation. 8,9 Bisphosphonates belong to a class of compounds that exert a significant inhibitory effect on osteoclasts and are therefore potent antiresorptive agents. 10 They reduce bone turnover, increase bone mineral density (BMD), and decrease fracture risk both at the lumbar spine and the hip.…”