RESUMO
BACKGROUND: Raised levels of pro-inflammatory, pro-resorptive cytokines during pulmonary infection may contribute to osteoporosis in cystic fibrosis (CF). We assessed osteoclast number and activity during infective exacerbations and examined their relationship to serum inflammatory cytokines and bone turnover markers. METHODS: Serum samples from 24 adults with CF were obtained before, during and after treatment of infection. Osteoclastic cells were generated from peripheral blood mononuclear cells and their number and activity assessed. Serum osteocalcin, type 1 collagen cross-linked N-telopeptide (NTx), interleukin-6 (IL-6), tumour necrosis factor alpha (TNFalpha), receptor activator of NFkB ligand (RANKL) and osteoprotegerin (OPG) were measured. RESULTS: Osteoclast number and activity were increased at the start of exacerbation and decreased with antibiotic therapy. Significant correlations were demonstrated between osteoclast formation and serum TNFalpha, OPG, osteocalcin and NTx and between osteoclast activity and serum IL-6 and NTx. CONCLUSIONS: The systemic response to infection is associated with increased bone resorptive activity in patients with CF.
Assuntos
Infecções Bacterianas/complicações , Remodelação Óssea , Fibrose Cística/microbiologia , Fibrose Cística/fisiopatologia , Citocinas/sangue , Mediadores da Inflamação/sangue , Osteoclastos/patologia , Adulto , Contagem de Células , Colágeno Tipo I/sangue , Fibrose Cística/patologia , Feminino , Humanos , Interleucina-6/sangue , Masculino , Osteocalcina/sangue , Osteoprotegerina/sangue , Peptídeos/sangue , Infecções por Pseudomonas/complicações , Pseudomonas aeruginosa , Índice de Gravidade de Doença , Fator de Necrose Tumoral alfa/metabolismo , Adulto JovemRESUMO
RATIONALE: Adults with cystic fibrosis (CF) are at increased risk of developing osteoporosis. During infective exacerbations, increased production of proinflammatory cytokines and markers of bone resorption have been reported. OBJECTIVE: The aim of this study is to investigate the growth and proliferation of potential osteoclast precursor cells before, during, and after intravenous antibiotic treatment of infective exacerbations in patients with CF. METHODS: Hematopoietic precursor cell growth was examined using colony formation assays using Methocult culture medium. Circulating potential osteoclast precursors were identified using four-color flow cytometry by CD14, CD33, CD34, and CD45 expression. RESULTS: At the start of an infective exacerbation increases in hematopoietic precursor colony formation (15.42 colonies/10(5) cells plated, p = 0.025), proliferation (28.5%, p < 0.001), and the numbers of circulating potential osteoclast precursors (6.5%, p < 0.001) were seen in comparison with baseline levels. These increases declined after treatment with intravenous antibiotics to a level close to baseline. CONCLUSIONS: The results demonstrate an increase in the production of potential osteoclast precursors in the peripheral blood during CF infective exacerbations. This may result in increased bone resorption and contribute to bone loss in patients with CF.
