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Published ahead of print on May 4, 2006, doi:10.1164/rccm.200512-1943OC

Am. J. Respir. Crit. Care Med., Volume 174, Number 3, August 2006, 306-311

A more recent version of this article appeared on August 1, 2006
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Submitted on December 21, 2005
Accepted on May 3, 2006

Osteoclastogenesis during Infective Exacerbations in Patients with Cystic Fibrosis

Elizabeth F Shead1*, Charles S Haworth2, Elaine Gunn2, Diana Bilton2, Mike A Scott3, and Juliet E Compston4

1 Department of Haematology, Addenbrooke's Hospital NHS Foundation Trust, Cambridge, United Kingdom; Department of Anatomy, University of Bristol, Bristol, United Kingdom, 2 Adult Cystic Fibrosis Centre, Papworth Hospital NHS Foundation Trust, Cambridge, United Kingdom, 3 Department of Haematology, Addenbrooke's Hospital NHS Foundation Trust, Cambridge, United Kingdom, 4 Department of Medicine, University of Cambridge, Cambridge, United Kingdom

* To whom correspondence should be addressed. E-mail: lizzshead{at}hotmail.com.

Rationale: Adults with cystic fibrosis (CF) are at increased risk of developing osteoporosis. During infective exacerbations increased production of pro-inflammatory cytokines and markers of bone resorption have been reported. Objective: The aim of this study was 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: Haematopoietic precursor cell growth was examined using colony formation assays using MethocultTM culture medium. Circulating potential osteoclast precursors were identified using four-colour flow cytometry by CD14, CD33, CD34 and CD45 expression. Results: At the start of an infective exacerbation increases in haematopoietic precursor colony formation (15.42 colonies/105 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 to baseline levels. These increases declined after treatment with intravenous antibiotics to a level close to baseline. Conclusions: Our 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.
Key words: Osteoporosis, cystic fibrosis, osteoclasts, cytokines




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