E.F. Shead (1), C.S. Haworth (2), E. Gunn (2), H.C. Barker (2) , D. Bilton (2) , M.A. Scott (1), J.E. Compston (3) .
(1) Department of Haematology, Addenbrookes Hospital, Cambridge, United Kingdom;(2) Adult CF Centre, Papworth Hospital, Cambridge, United Kingdom; (3) Department of Medicine, University of Cambridge, Cambridge, United Kingdom
Rationale: CF adults are at increased risk of osteoporosis. The mean concentration of IL-6 is an independent predictor of change in bone mineral content, suggesting that pulmonary infection may influence bone metabolism in adults with CF.
Objective: The aim of this study was to investigate the variation in levels of inflammatory cytokines and bone metabolism markers before, during, and after intravenous antibiotic treatment of infective exacerbations in patients with CE
Methods: Blood samples were collected at baseline when clinically stable, at day 1 of IV antibiotic therapy, at day 14 (end of IVs) and day 42 (follow-up). Serum osteocalcin and NTx were measured using commercially available ELISAs, in addition to IL-1?, IL-6, TNF?, receptor activator for nuclear factor ?B ligand (RANKL), TGFIi and osteoprotegerin (OPG).
Results: During an exacerbation significant variations in serum levels of NTx (p=0.027), RANKL (p= 0.05), OPG (p= 0.03), IL-6 (p = 0.005) and TNF? (p=0.003) were seen. A significant increase in NTx was seen at day 1 and day 14 of exacerbation (p <0.05) compared to baseline. Baseline osteocalcin levels in CF patients were significantly lower than those in the normal controls (p <0.05). An increase in RANKL (p <0.05) and OPG (p <0.05) was seen at day 14, decreasing the RANKL:OPG ratio.
Conclusion: The results demonstrate increased levels of proinflammatory cytokines during CF infective exacerbations. The increase in NTx at day 1 and the decrease RANKL:OPG ratio at day 14 indicates that osteoclast activity is increased at the start of exacerbations and reduces after IV antibiotic therapy.