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Osteoclastogenesis during Infective Exacerbations in Patients with Cystic Fibrosis

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

Correspondence and requests for reprints should be addressed to Elizabeth F. Shead, B.Sc., Box 234, Haematology Department, Addenbrooke's Hospital, NHS Foundation Trust, Hills Road, Cambridge CB2 2QQ, UK. 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 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/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 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.

Key Words: cystic fibrosis • cytokines • osteoclasts • osteoporosis

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