Bone Density, Body Composition, and Inflammatory Status in Cystic Fibrosis

Abstract

Low body weight and loss of bone mass are major problems in adults with cystic fibrosis (CF) and chronic pulmonary infection. Although these complications probably have a multifactorial origin, we hypothesized that the continuous acute-phase inflammatory and catabolic state may contribute. We determined body composition, bone turnover, physical activity, and circulating interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), and their soluble receptors in 22 adults with CF and 22 age- and sex-matched healthy subjects. Comparisons were also made within patients before and after treatment of an exacerbation of respiratory symptoms. The patients had a lower mean (95% confidence interval [CI]) fat-free mass (FFM) 39.9 (36.3, 43.6) kg than healthy subjects, 49.4 (45.1, 53.7) kg, p < 0.05. The patients were in negative nitrogen balance and 20 had bone mineral density (BMD) Z scores </= 2.5 SD (n = 13) or </= 1 SD (n = 7) at least at one site. They had increased bone collagen breakdown, greatest in those with a reduced FFM. BMD was related to FEV(1) (r = 0.44), IL-6 (r = -0.60), and TNF-alpha-soluble receptors (r = -0.42, r = -0.50). Patients with a low FFM had greater concentrations of IL-6, which suppressed less after antibiotic treatment than in those with a normal FFM. Those with a low FFM were more catabolic and less active than those with a normal FFM. The association between altered body composition, catabolic status, and circulating inflammatory mediators suggests that chronic pulmonary infection in adults with CF may be a contributory factor in the long-term complications of low weight and bone disease.

Increased augmentation index in patients with cystic fibrosis

“…Many of the comorbidities, including low skeletal muscle mass and function [2] and osteoporosis [3], would be expected to occur in a comparatively older population as part of physiological ageing, yet are evident in patients with CF in their second and third decade of life. Similar comorbidities are a feature of other disorders with a chronic systemic inflammatory component, such as rheumatoid arthritis and chronic obstructive pulmonary disease (COPD), where there is again apparent dissociation of physiological and chronological ageing [4][5][6].…”

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

“…A longitudinal study of BMD in CF patients concluded that both reduced bone accretion and accelerated bone loss contribute to the reduced BMD [8]. Elevated levels of bone turnover markers, including serum osteocalcin, urinary N-telopeptide and bonespecific alkaline phosphatase, have been reported in CF patients [5,6,9,10], and it has been suggested that, in CF, there is an imbalance between bone formation and bone resorption in favour of resorption [11,12]. An association between reduced 25-hydroxyvitamin D levels and reduced BMD has been reported in CF patients [7].…”

“…An association between reduced 25-hydroxyvitamin D levels and reduced BMD has been reported in CF patients [7]. Poor nutritional status has also been reported to be associated with reduced BMD [4,5,7,10,13,14]. Delayed puberty has been associated with reduced BMD in some studies [2,15], but, in other studies, age of menarche in females did not correlate with BMD [4,6,7].…”

Resultado de intervenção nutricional em crianças e adolescentes com fibrose cística

“…A massa gorda e o percentual de gordura corporal apresentaram-se sem alterações significantes durante o seguimento (Tabela 3). Estudos que compararam os pacientes a um grupo controle observaram que crianças [51][52][53] , adolescentes 52 e adultos [54][55][56] possuem valores abaixo do recomendado para massa magra e gorda, reforçando a idéia de que, mesmo com a melhora da composição corporal, não são todos os pacientes que conseguem atingir a normalidade, como o observado.…”