To study bone mineral density (BMD) of pre-pubertal cystic fibrosis (CF) children, and its relation with clinical and laboratory parameters, we enrolled 16 CF (8 girls) (4-8 years), and 16 control children (8 girls) (4-8 years). After anthropometric measurements, BMD, serum calcium, phosphorus, total alkaline phosphatase (ALP), 25-hydroxy vitamin D (25-OHD), parathyroid hormone, osteocalcin, tumor necrosis factor (TNF)-alpha, soluble TNF-alpha receptor 2 (sTNFR2), and soluble IL-2 receptor (sIL-2R) levels, and urinary calcium and hydroxyproline excretions were assessed. Disease severity of CF patients was determined with Shwachman-Kulczycki clinical and Brasfield radiological scoring systems. The mean Shwachman-Kulczycki and Brasfield scores of CF patients were indicating well-controlled disease. The anthropometric measurements, mean BMD values, and serum calcium, phosphorus and parathyroid hormone levels were within normal range and similar in both groups. Serum osteocalcin levels were lower, and ALP and 25-OHD levels were higher in CF Although 24-hr urinary calcium excretions was higher in CF patients, hydroxyproline excretions were similar in both groups. There was no difference between two groups for the serum levels of sIL-2R, TNF-alpha and sTNFR2. Children with low vertebral z-scores had higher serum sIL-2R levels in both groups, but the same relation could not be shown for TNF-alpha and sTNFR2. We may speculate that younger, healthier and well-nourished patients with CF may have normal BMD, but the bone disease develop as patients get older because of the other contributing factors. Future well-designed longitudinal studies with large cohorts might show a relation with BMD and cytokines in CF Pediatr Pulmonol. 2009; 44:706-712. (C) 2009 Wiley-Liss Inc.