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The Journal of Clinical Endocrinology & Metabolism Vol. 89, No. 7 3385-3391
Copyright © 2004 by The Endocrine Society

Calcium Kinetics Are Altered in Clinically Stable Girls with Cystic Fibrosis

Kerry J. Schulze, Kimberly O. O’Brien, Emily L. Germain-Lee, Sarah L. Booth, Amanda Leonard and Beryl J. Rosenstein

Center for Human Nutrition (K.J.S., K.O.O.), The Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland 21205; Division of Pediatric Endocrinology (E.L.G.-L.), The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205; Jean Mayer U.S. Department of Agriculture Human Nutrition Research Center on Aging (S.L.B.), Tufts University, Boston, Massachusetts 02111; and Department of Pediatrics (A.L., B.J.R.), The Johns Hopkins Hospital, Baltimore, Maryland 21205

Address all correspondence and requests for reprints to: Kimberly O’Brien, Associate Professor, The Johns Hopkins University Bloomberg School of Public Health, Center for Human Nutrition, 615 North Wolfe Street, Room W2517, Baltimore, Maryland 21205. E-mail: kobrien{at}jhsph.edu.

Reduced bone mass in individuals with cystic fibrosis (CF) may result from alterations in calcium metabolism. Bone calcium deposition and resorption rates, calcium balance, and markers of bone turnover were assessed using stable isotopes of calcium in 22 prepubertal and pubertal girls with CF. Bone calcium deposition was associated with the availability of dietary calcium, total serum osteocalcin, and leptin concentrations.

Reduced bone mass in individuals with CF may result from inadequate bone calcium (Ca) deposition, and excessive resorption, although these parameters have not been directly assessed in children with CF.

We used stable Ca isotopes to measure rates of bone Ca deposition (Vo+), resorption, and retention in 22 clinically stable girls with CF (aged 7–18 yr). Rates of bone Ca deposition were determined by mathematically modeling the disappearance of iv Ca stable isotope (42Ca) for 6 d post dosing. Indirect markers of bone turnover and hormones associated with pubertal development were also assessed.

Rates of bone Ca deposition and retention were highest during early puberty (Tanner stages 2 and 3). Calcium deposition rates in prepubertal (Tanner 1) and postmenarchal girls (Tanner stages 4 and 5) did not support substantial bone Ca retention. Net absorption of dietary Ca and serum osteocalcin and leptin concentrations were positively associated with Vo+. Time post menarche and serum leptin concentrations explained 91% of the variability in Vo+ (P = 0.0007). Serum total osteocalcin was low (10.9 ± 5.4 ng/ml), and a substantial percentage of osteocalcin was undercarboxylated (54.3 ± 11.8%).

We concluded that increased calcium absorption and serum leptin concentrations were significantly associated with rates of bone Ca deposition, demonstrating an impact of nutritional status on this process. Rates of bone Ca deposition were lower than typically reported in healthy children, as were indirect markers of bone formation. These alterations in bone turnover contribute to reduced bone mass in girls with CF.

This work was supported by the Cystic Fibrosis Foundation and the National Center for Research Resources/General Clinical Research Center Grant RR00052.

The contents of this publication do not necessarily reflect the views or policies of the U.S. Department of Agriculture, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government.

Abbreviations: BMI, Body mass index; CF, cystic fibrosis; DXA, dual-energy x-ray absorptiometry; ln, natural logarithm; LS BMD, lumbar spine bone mineral density; NTX, N-telopeptide; OC, osteocalcin; 1,25(OH)2D, 1,25-dihydroxyvitamin D; 25(OH)D, serum 25-hydroxyvitamin D; TBBMC, total body bone mineral content; TBBMC%, percentage of TBBMC expected based on the prediction equation; ucOC, undercarboxylated OC; ucOC%, percentage of OC not bound to hydroxyapatite in vitro; Vbal, bone Ca balance; Vendo, endogenous fecal Ca loss; Vo+, bone Ca deposition; Vo–, bone Ca resorption.




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