Am. J. Respir. Crit. Care Med., Volume 162, Number 5, November 2000, 1674-1678

Adverse Alterations in Bone Metabolism Are Associated with Lung Infection in Adults with Cystic Fibrosis

ROBERT M. ARIS, ASHLEY R. STEPHENS, DAVID A. ONTJES, A. DENENE BLACKWOOD, ROBERT K. LARK, MARGARET B. HENSLER, ISABEL P. NEURINGER, and GAYLE E. LESTER

Divisions of Pulmonary Medicine and Endocrinology, the Departments of Medicine and Orthopedics, and School of Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina

Low bone density, fractures, and kyphosis complicate the lives of adults with cystic fibrosis (CF), and inflammatory cytokines (interleukin [IL]-1, IL-6, and tumor necrosis factor [TNF]-) that may alter bone metabolism have been previously found to be increased in the lungs and serum of CF patients. The objective of this prospective study was to determine the impact of lung infection on bone physiology in 17 adult CF patients. Serum osteocalcin, a marker of bone formation; urine N-telopeptides of type I collagen and free deoxypyridinoline, both of which are markers of bone breakdown; serum cytokines (TNF-, IL-1, and IL-6); and general inflammatory markers (serum C-reactive protein [CRP] and chondrex) were measured at the beginning and end of treatment for an acute exacerbation of lung infection and again 3 wk later. After treatment with conventional antibiotics, decreases in N-telopeptides (147.3 ± 77.5 [mean ± SEM] versus 95.5 ± 57.3 bone collagen equivalents (BCE)/mmol creatinine, p = 0.0014), deoxypyridinoline (8.42 ± 2.8 versus 6.8 ± 3.0 mmol/mmol creatinine, p = 0.08), IL-1 (1.43 ± 1.13 versus 0.65 ± 0.63 pg/ml, p = 0.03), IL-6 (9.5 ± 6.5 versus 4.7 ± 3.2 pg/ml, p = 0.012), CRP (43.1 ± 29.3 versus 23.4 ± 25.3 mg/ml, p = 0.04), and chondrex (151.7 ± 111.7 versus 101.4 ± 67.3 ng/ml, p = 0.014), and increases in osteocalcin levels (14.5 ± 5.4 versus 22.5 ± 8.7 ng/ml, p = 0.010) were observed. Three weeks later, the changes in N-telopeptides and osteocalcin persisted. These data indicate that pulmonary infection, through the elaboration of inflammatory cytokines, may be linked to increased bone resorption and diminished bone formation. These results provide insights into the impact of systemic inflammation on bone health, and suggest novel mechanisms for bone disease in CF.

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