Calcium kinetics are altered in clinically stable girls with cystic fibrosis.

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 ((42)Ca) 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.

[1]  D. Baer,et al.  Endogenous fecal losses of calcium compromise calcium balance in pancreatic-insufficient girls with cystic fibrosis. , 2003, The Journal of pediatrics.

[2]  D. Baer,et al.  Efficiency of calcium absorption is not compromised in clinically stable prepubertal and pubertal girls with cystic fibrosis. , 2003, The American journal of clinical nutrition.

[3]  P. O’Rourke,et al.  Abnormalities of the PTH-vitamin D axis and bone turnover markers in children, adolescents and adults with cystic fibrosis: comparison with healthy controls , 2003, Osteoporosis International.

[4]  J. Compston,et al.  Histomorphometric analysis of bone biopsies from the iliac crest of adults with cystic fibrosis. , 2002, American journal of respiratory and critical care medicine.

[5]  S. Khosla Leptin-central or peripheral to the regulation of bone metabolism? , 2002, Endocrinology.

[6]  Patricia Ducy,et al.  Leptin Regulates Bone Formation via the Sympathetic Nervous System , 2002, Cell.

[7]  J. Renner,et al.  Abnormal Bone Turnover in Cystic Fibrosis Adults , 2002, Osteoporosis International.

[8]  S. Abrams,et al.  Z Score Prediction Model for Assessment of Bone Mineral Content in Pediatric Diseases * , 2001, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[9]  B. Caballero,et al.  Bone mineral content in girls perinatally infected with HIV. , 2001, The American journal of clinical nutrition.

[10]  Alan D. Martin,et al.  Calcium Accretion in Girls and Boys During Puberty: A Longitudinal Analysis , 2000, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[11]  R. Lark,et al.  Adverse alterations in bone metabolism are associated with lung infection in adults with cystic fibrosis. , 2000, American journal of respiratory and critical care medicine.

[12]  A. Ionescu,et al.  Bone density, body composition, and inflammatory status in cystic fibrosis. , 2000, American journal of respiratory and critical care medicine.

[13]  H. White,et al.  Osteoporosis and osteopenia in adults and adolescents with cystic fibrosis: prevalence and associated factors , 2000, Thorax.

[14]  P. Hasleton,et al.  Bone histomorphometry in adult patients with cystic fibrosis. , 2000, Chest.

[15]  S. Abrams,et al.  Calcium absorption, bone mass accumulation, and kinetics increase during early pubertal development in girls. , 2000, The Journal of clinical endocrinology and metabolism.

[16]  J. Adams,et al.  Low bone mineral density in adults with cystic fibrosis , 1999, Thorax.

[17]  A. Blakemore,et al.  Leptin binding activity changes with age: the link between leptin and puberty. , 1999, The Journal of clinical endocrinology and metabolism.

[18]  C. Madsen,et al.  Bone mineral content and body composition in children and young adults with cystic fibrosis , 1999, Pediatric pulmonology.

[19]  Vitamin K status and bone health: an analysis of methods for determination of undercarboxylated osteocalcin. , 1998, The Journal of clinical endocrinology and metabolism.

[20]  S. Abrams,et al.  Development and regulation of calcium metabolism in healthy girls. , 1998, The Journal of nutrition.

[21]  A. Leblanc,et al.  Serum leptin and IGF-I levels in cystic fibrosis. , 1998, Endocrine research.

[22]  Ramzi W. Nahhas,et al.  Leptin is inversely related to age at menarche in human females. , 1997, The Journal of clinical endocrinology and metabolism.

[23]  L. Sokoll,et al.  Effect of vitamin K1 supplementation on vitamin K status in cystic fibrosis patients. , 1997, Journal of pediatric gastroenterology and nutrition.

[24]  D. Dunger,et al.  Relation between insulin-like growth factor-I, body mass index, and clinical status in cystic fibrosis , 1997, Archives of disease in childhood.

[25]  G. Saggese,et al.  Bone Demineralization in Cystic Fibrosis: Evidence of Imbalance between Bone Formation and Degradation , 1997, Pediatric Research.

[26]  S. Abrams,et al.  Changes in calcium kinetics associated with menarche. , 1996, The Journal of clinical endocrinology and metabolism.

[27]  S. Abrams,et al.  Total body calcium and bone mineral content: Comparison of dual‐energy X‐ray absorptiometry with neutron activation analysis , 1996, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[28]  R. Marcus,et al.  Correlates of osteopenia in patients with cystic fibrosis. , 1996, Pediatrics.

[29]  S. Shalet,et al.  Role of growth hormone and sex steroids in achieving and maintaining normal bone mass. , 1996, Hormone research.

[30]  C. Madsen,et al.  Bone density in children and adolescents with cystic fibrosis. , 1996, The Journal of pediatrics.

[31]  N. Mauras,et al.  Sex steroids, growth hormone, insulin-like growth factor-1: neuroendocrine and metabolic regulation in puberty. , 1996, Hormone research.

[32]  K. Michaelsen,et al.  Serum levels of insulin-like growth factor (IGF)-binding protein-3 (IGFBP-3) in healthy infants, children, and adolescents: the relation to IGF-I, IGF-II, IGFBP-1, IGFBP-2, age, sex, body mass index, and pubertal maturation. , 1995, The Journal of clinical endocrinology and metabolism.

[33]  S. Abrams,et al.  Calcium metabolism in girls: current dietary intakes lead to low rates of calcium absorption and retention during puberty. , 1994, The American journal of clinical nutrition.

[34]  A. Yergey,et al.  Compartmental Analysis of Calcium Metabolism in Very-Low-Birth-Weight Infants , 1994, Pediatric Research.

[35]  R. Heaney,et al.  Timing of peak bone mass in Caucasian females and its implication for the prevention of osteoporosis. Inference from a cross-sectional model. , 1994, The Journal of clinical investigation.

[36]  D. Eyre,et al.  Bone resorption rates in children monitored by the urinary assay of collagen type I cross-linked peptides. , 1994, Bone.

[37]  S. Abrams Pubertal Changes in Calcium Kinetics in Girls Assessed Using 42Ca , 1993, Pediatric Research.

[38]  M. Jonckheer,et al.  Low serum bone gamma-carboxyglutamic acid protein concentrations in patients with cystic fibrosis: correlation with hormonal parameters and bone mineral density. , 1993, Hormone research.

[39]  J. Lian,et al.  Osteocalcin: isolation, characterization, and detection. , 1984, Methods in enzymology.

[40]  R. Stern,et al.  The reproductive endocrine system in cystic fibrosis. I. Basal gonadotropin and sex steroid levels. , 1981, American journal of diseases of children.

[41]  A. Yergey,et al.  Isotope ratio measurements of urinary calcium with a thermal ionization probe in a quadrupole mass spectrometer. , 1980, Analytical chemistry.

[42]  M Berman,et al.  Multicompartmental analysis of calcium kinetics in normal adult males. , 1967, The Journal of clinical investigation.