Twenty-four-Hour Osteocalcin, Carboxyterminal Propeptide of Type I Procollagen, and Aminoterminal Propeptide of Type III Procollagen Rhythms in Normal and Growth-Retarded Children

Saggese, Giuseppe; Baroncelli, Gi; Bertelloni, Silvano; Cinquanta, Luciano; Dinero, G.

doi:10.1203/00006450-199404000-00006

Cited by 49 publications

(28 citation statements)

References 25 publications

(53 reference statements)

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“…Osteocalcin, a sensitive bone formation marker, was reported previously in adults and children to have a zenith at night and nadir in the morning (17,18). In the present study, a similar nocturnal zenith in plasma osteocalcin was observed in infant piglets.…”

Section: Discussionsupporting

confidence: 75%

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Comparative Response in Growth and Bone Status to Three Dexamethasone Treatment Regimens in Infant Piglets

et al. 2000

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The objectives of this study were 1) to determine whether a zenith in bone formation (indicated by circulating osteocalcin) existed at night in early life, and 2) to compare the effects of three different dexamethasone (DEX) treatment regimens on bone turnover, bone mineral content, and growth. Three DEX treatment regimens were tested in 8-d-old piglets (n ϭ 8/group): 1) low evening dose of DEX (0.5 mg/kg/d) as 70% in the morning and 30% in the evening for 10 d; 2) tapering course of DEX (0.5, 0.3, and 0.2 mg/kg/d) as 50% in the morning and 50% in the evening for 14 d; and 3) constant dose of DEX (0.5 mg/kg/d) as 50% in the morning and 50% in the evening for 10 d. Oral water placebo groups were tested with the same time courses. At pretreatment, plasma osteocalcin was significantly higher (p Ͻ 0.05) at 0100 than at 0900 and 1700. At necropsy, measures for DEX groups were calculated as Z-scores using values from the placebo groups. The low evening DEX dose led to a significantly lower reduction in plasma osteocalcin compared with the tapered and constant dosing regimens (p Ͻ 0.05). The significant weight reduction in the DEX group occurred at d 9 in the low evening dose regimen but at d 7 in the constant dosing regimen, compared with the placebo group. Bone mineral content Z-score was reduced similarly in all DEX-treated groups across the three dosing regimens. We conclude that a plasma osteocalcin zenith at night exists in early life. A high DEX dose in the morning and low DEX dose in the evening may partially attenuate corticosteroid-induced suppression of bone formation and growth restriction. Abbreviations BMC, bone mineral content Cr, creatinine CV, coefficient of variation DEX, dexamethasone NTx, N-terminal telopeptide of type I collagen VLBW, very low birth weight VLBW infants may develop severely compromised lung function because of their immaturity. The incidence of bronchopulmonary dysplasia in VLBW infants has been reported to be as high as 70% (1). DEX is prescribed for these infants to improve pulmonary compliance and to facilitate earlier weaning from the ventilator (2, 3). However, linear, weight and bone growth can be adversely affected by DEX administration in VLBW infants (4 -7). Despite these side effects, DEX continues to be used in treatment of chronic lung disease (8 -10). Although both tapered (3-6) and constant (8) dosing regimens are used in clinical practice, it is not known whether they induce similar restrictions in growth and bone development.The rapidly growing piglet is a good model for human infants (11). From our experience with piglets, monitoring growth for a 2-wk period (12, 13) parallels the changes in weight (4-fold increase) and length (1.2-fold increase) that we observe in VLBW human infants over 8.5 wk or from their birth to term-adjusted age (4). Piglets respond like human infants in the metabolic processing of minerals, and they have been used successfully to measure responses in growth and bone development to alterations in dietary minerals (14), administration of DEX (...

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Section: Discussionsupporting

confidence: 75%

“…A circadian rhythm in bone formation has been reported in adults and children, with a zenith at night and nadir in the morning (17,18). Circadian rhythm in bone formation has not been assessed in infants; possibly because of the difficulty of collecting serial blood samples from newborn infants.…”

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confidence: 99%

Comparative Response in Growth and Bone Status to Three Dexamethasone Treatment Regimens in Infant Piglets

et al. 2000

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“…Indeed, OC, PICP, and ICTP levels follow a similar circadian rhythm with peak values occurring in early morning and nadirs in the afternoon (1,30,37). Circadian variation in bone markers appears to be unaffected by age and sex (38), as well as by growth and ageing (39).…”

Section: Discussionmentioning

confidence: 93%

“…In any case, the diminished somatic growth likely contributed to reducing the levels of the bone markers. In this context, we have demonstrated that 24-h PICP but not 24-h OC concentrations were growth velocity-dependent and GH-dependent in children with GHD (30).…”

Section: Discussionmentioning

confidence: 99%

“…Circadian variation in bone markers appears to be unaffected by age and sex (38), as well as by growth and ageing (39). Furthermore, in children with GHD, we previously demonstrated that both nocturnal and diurnal 12-h mean data for OC and PICP were significantly lower than controls, but the pattern of their circadian rhythms was maintained (30). In any case, in the present study, serum samples for the measurement of the bone markers were drawn under standardized conditions in both patients and controls.…”

Section: Discussionmentioning

confidence: 99%

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Dynamics of bone turnover in children with GH deficiency treated with GH until final height

Baroncelli

Bertelloni

Ceccarelli

et al. 2000

European Journal of Endocrinology

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Objective: To examine the dynamics of bone turnover in children with growth hormone deficiency (GHD) during long-term treatment. Design: We longitudinally measured growth velocity and serum concentrations of osteocalcin (OC), carboxyterminal propeptide of type I procollagen (PICP), and cross-linked carboxyterminal telopeptide of type I collagen (ICTP) in 24 patients with GHD during long-term GH treatment until final height (age: 7.7 Ϯ 0.7 and 16.9 Ϯ 0.5 years at baseline and at final height respectively). Results: At baseline, OC, PICP, and ICTP levels were significantly (P < 0.0001) reduced in comparison with prepubertal bone age-matched controls (10.2 Ϯ 2.3 mg/l and 22.5 Ϯ 7.6 mg/l; 187.8 Ϯ 26.2 mg/l and 328.4 Ϯ 74.3 mg/l; 7.7 Ϯ 2.0 mg/l and 14.2 Ϯ 1.3 mg/l respectively). During the first year of treatment mean levels of the bone markers increased significantly (P < 0.0001) with a peak at 12 months. After the first year of treatment, OC and PICP levels progressively declined, whereas ICTP levels remained stable until the final height; in any case, bone marker levels remained significantly higher (P < 0.03-P < 0.0001) than baseline. The change in bone marker levels at 6 and 12 months of treatment with respect to the baseline values was not related to growth rate during long-term treatment or final height. Conclusions:The results show that children with GHD have reduced bone turnover at baseline, and that long-term GH treatment is associated with a stimulation of bone turnover. OC, PICP, and ICTP do not predict growth rate during long-term treatment or final height in children with GHD.

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Carboxy-terminal propeptide of human type I collagen and pyridinium cross-links as markers of bone growth in infants 1 to 18 months of age

Lieuw-a-Fa

Sierra

Specker

1995

Journal of Bone and Mineral Research

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Serum carboxy-terminal propeptide of human type I collagen (PICP) concentrations, as a marker for bone formation, and urinary pyridinium (Pyd) cross-link concentrations, as a marker of bone resorption, were determined in 66 healthy infants aged 1-18 months who are being studied longitudinally. We hypothesized that there would be a positive correlation of growth velocity, increase in bone area, and bone mass accretion rates with PICP and Pyd cross-link concentrations. Since osteocalcin is currently used as a marker of bone formation, serum osteocalcin concentrations were also measured. Mean serum PICP and urinary Pyd cross-link concentrations were significantly greater than adult concentrations. Future growth velocity, increase in bone area, and bone mass accretion rates were not associated with PICP, Pyd cross-link, or osteocalcin concentrations. Growth velocity during the 3 months preceding sample collection correlated with serum PICP, Pyd/kg, and osteocalcin concentrations (r = 0.474, p< 0.001; r = 0.379, p < 0.001; and r = 0.516, p < 0.001, respectively). Previous increase in bone area correlated with serum PICP concentrations (r = 0.359, p = 0.01). The relationship between the infant's previous bone mass accretion rate and PICP was of borderline significance (r = 0.281, p = 0.055). In summary, normative data for PICP, Pyd cross-link concentrations, and parameters of bone growth are provided for infants 1-18 months of age and indicate that these markers reflect past and current bone metabolism and may be helpful in monitoring bone disorders in infants.

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Twenty-four-Hour Osteocalcin, Carboxyterminal Propeptide of Type I Procollagen, and Aminoterminal Propeptide of Type III Procollagen Rhythms in Normal and Growth-Retarded Children

Cited by 49 publications

References 25 publications

Comparative Response in Growth and Bone Status to Three Dexamethasone Treatment Regimens in Infant Piglets

Comparative Response in Growth and Bone Status to Three Dexamethasone Treatment Regimens in Infant Piglets

Dynamics of bone turnover in children with GH deficiency treated with GH until final height

Carboxy-terminal propeptide of human type I collagen and pyridinium cross-links as markers of bone growth in infants 1 to 18 months of age

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