Markers Of Bone Turnover In Children Research Articles

Biochemical bone turnover markers in children and adolescents

Biochemical bone turnover markers in children and adolescents

Predicting bone mineral acquisition during puberty: data from a 3-year follow-up study in Hamamatsu, Japan.

Although most adult bone mass is acquired before adolescence, only a few studies have assessed bone turnover markers in children. Thus, the utility of bone markers to evaluate and predict bone mineral accrual in children is unclear. The present study assessed the association between serum bone markers at 11years of age and subsequent changes in bone gain. Information on bone minerals and bone markers at baseline and at the 3-year follow-up were obtained from 121 children who registered as fifth-grade students in 2010, in Hamamatsu, Japan. Whole-body bone mineral content (WBBMC) and whole-body bone mineral density (WBBMD) were measured using dual-energy X-ray absorptiometry. Boys showed significant (P<0.05) positive relationships between intact osteocalcin at baseline and WBBMC at follow-up (β=0.24), between tartrate-resistant acid phosphatase isoenzyme 5b (TRAP5b) and WBBMC (β=0.34), and between TRAP5b and WBBMD (β=0.34), after adjusting for potential confounding factors. In girls, adjusted means of 3-year gain in both WBBMC and WBBMD significantly increased from the lowest to highest quartiles of type 1 collagen cross-linked C-terminal telopeptide. In boys, adjusted means of 3-year gain in both WBBMC and WBBMD significantly increased from the lowest to highest quartiles of TRAP5b. Children with a high concentration of bone turnover markers tended to exhibit substantial accrual of bone minerals. These results suggest that serum levels of circulating biomarkers at age 11 predict subsequent bone mineral accrual.

Associations between Ambient Air Pollution and Bone Turnover Markers in Children: Results from the Giniplus and Lisaplus Studies

Associations between Ambient Air Pollution and Bone Turnover Markers in Children: Results from the Giniplus and Lisaplus Studies

Decreased Bone Turnover Markers in Children on Long‐Term Parenteral Nutrition (PN) for Intestinal Failure (IF)

Metabolic bone disease (MBD) is a well-recognized but poorly understood complication of long-term parenteral nutrition (PN). Bone histomorphometry in adults has provided useful information but does not provide quantitative measures of bone resorption and is to invasive for children. Measurement of bone turnover markers provides an alternative less invasive approach. We therefore aimed to measure bone turnover markers in children on long-term PN for intestinal failure (IF), and to compare them to age- and gender-matched controls. Serum concentrations of osteocalcin (OC), bone-specific alkaline phosphatase (BSAP), and c-telopeptide (CTx) were measured in IF patients treated at a multidisciplinary intestinal rehabilitation and home PN program at the Hospital for Sick Children, Toronto, Canada. Age- and gender-matched control participants were recruited for comparison. A total of 13 IF patients and 20 control participants were recruited. IF patients had lower serum OC and CTx concentrations when compared with controls: 42.43 ± 11.54 vs 68.39 ± 20.95 µg/L (P < .01) and 7.454 ± 2.17 vs 9.246 ± 1.92 (P < .05; mean ± SD) µg/L for OC and CTx, respectively. In a subgroup of 9 IF patients for whom BMD was available, OC and CTx concentration were negatively correlated to BMD (g/cm(2)) and BMD z score. Bone turnover markers may be useful indicators for identifying children on long-term PN at risk of MBD. Further studies are needed to validate the current results and determine the factors that influence the occurrence and evolution of MBD in children on PN.

Bone turnover markers in children with osteogenesis imperfecta

Bone turnover markers in children with osteogenesis imperfecta

Interpretation and application of bone turnover markers in children and adolescents

To assess recent research findings on various biochemical bone turnover markers and to assess their use in monitoring bone growth in children and adolescents. There are very few recent studies that investigate various serum and urine analytes that reflect bone formation and resorption to monitor bone health during longitudinal growth. In infants and young children, the measurement of bone markers in serum is suggested because of the practical difficulties associated with urine collection and by the circadian and intraindividual variation in urinary markers. During the prepubertal growth, bone turnover values are similar in age-matched boys and girls. The increase in different bone turnover markers coincides with the pubertal growth spurt. This starts later in boys and the increase in bone turnover markers also occurs later, is greater and lasts longer when compared with girls. Recent studies demonstrated that bone size increases and bone turnover decreases until mid-twenties. More than one bone formation and resorption marker should be measured to monitor longitudinal growth and bone mineral accrual, because sensitivities and predictive values of single markers are still poor. It is important to find new and more sensitive markers that could better characterize linear growth.

Clinical utility of biochemical bone turnover markers in children and adolescents with osteosarcoma

Biochemical markers of bone turnover reflecting the intensity of all bone remodeling processes in skeleton are important for fast and non-invasive assessment of bone formation and resorption processes. They can be used in terms of both physiological and pathological states. The aim of this study was to investigate if bone metabolism markers can be clinically useful for monitoring of treatment in children and adolescents with osteosarcoma. The study consisted of 55 patients (median age 15 years) with osteosarcoma and 60 healthy age matched counterparts. Serum bone turnover markers (bone alkaline phosphatase - BALP, osteocalcin - OC and C-terminal telopeptide of type I collagen - CTX) were analyzed by immunoenzymatic methods in patients at time of diagnosis, during treatment and after therapy. We observed that before treatment the concentration of OC in patients with osteosarcoma was significantly lower (p<0.05) compared to that obtained in healthy children, however, BALP and CTX were at a similar level. During chemotherapy the values of bone formation and resorption markers significantly decreased by about 20-30%. After therapy we observed different concentrations of all bone turnover markers in patients with favorable and unfavorable prognosis. Median values of OC and BALP were over twofold higher in patients with progression as compared to patients with remission of disease (p<0.01 and p<0.001, respectively). Patients with poor prognosis had also higher serum concentration of bone resorption marker in comparison to patients with remission (p<0.01). Presented results suggest that bone turnover markers identify changes in bone metabolism in patients with osteosarcoma during anticancer therapy. These markers due to the non-invasive methods and their specificity might be useful in monitoring of clinical treatment of osteosarcoma patients.

Bone metabolism markers and bone mineral density in children with neurofibromatosis type-1

Some experimental studies suggested that there may be a bone formation defect rather than a disorder in bone resorption in patients NF1. The aim of this study was to determine bone mineral density (BMD) with dual-energy X-ray absorptiometry (DEXA) and investigate specific bone formation and bone resorption and bone turnover markers in children with NF1. Thirty-two children and adolescents (16 boys, 16 girls; 16 prepubertal, 16 pubertal) with NF1 were recruited. Their age ranged from 3 to 17 years. They were compared with matched healthy children. Dual-energy X-ray absorptiometry were applied to 26 patients and 27 controls. Nine of 32 subjects with NF1 had a skeletal abnormality. BMD of the lumbar spine, and femoral neck in NF1 patients significantly decreased compared to that of healthy subjects. They were also significantly decreased in pubertal patients when compared to pubertal controls and in prepubertal patients when compared to prepubertal controls. Patients with skeletal abnormalities were found to have significantly lower level of osteocalcin when compared to patients without skeletal abnormality. Other biochemical markers did not exhibit any difference between the groups. In conclusion, our findings suggest that bone formation markers rather than DEXA could be good predictors of skeletal abnormalities among NF1 patients. However, in our study the number of the NF1 patients with skeletal abnormality and the number of bone formation markers studied were all limited. It is appropriate to perform larger studies with other bone formation markers beside osteocalcin.

Serum markers of bone turnover in children and adolescents with classic galactosemia

Classic galactosemia is an inherited metabolic disease resulting from galactose-1-phosphate uridyltransferase (GALT) deficiency. Dietary lactose exclusion reverses many clinical manifestations of acute phase of the disease. Unfortunately most of the patients, despite dietary treatment, develop long-term complications among them disturbances of bone mineralization resulting in decrease of bone mineral density (BMD). The aim of our study was to assess bone formation and resorption processes with bone turnover markers in children and adolescents with galactosemia. We studied 62 galactosemic children (mean age+/-SD 5.9+/-2.7 years) and adolescents (mean age+/-SD 15.6+/-2,4 years). The clinical diagnosis had been confirmed by the absence of GALT activity in erythrocytes. All patients were diagnosed in the neonatal period and had good dietary control. Healthy children (n=70) were the reference group. Serum osteocalcin (OC), bone alkaline phosphatase (BALP), collagen type I crosslinked C-telopeptide (CTX-I), 25(OH)D metabolite of vitamin D were determined by ELISA assays. We observed similar mean values of bone formation markers in children with galactosemia as compared to the age-matched controls. The level of bone resorption marker CTX-I in these patients was lower by about 20% (p<0.001) than in healthy children. On the contrary we obtained slightly higher values of CTX-I in adolescents with galactosemia in comparison to the age-matched controls. In these patients the values of OC and BALP were significantly higher than in healthy adolescents (111.8+/-52.1 microg/L versus 82.3+/-43.0 microg/L, p<0.02; and 95.4+/-45.7 U/L versus 72.6+/-40.6 U/L, p<0.05 respectively). Our results suggest that bone turnover in galactosemic patients elevates from childhood to adolescence, whereas in healthy individuals there is a decline during aging. Further studies on adults with galactosemia are necessary to assess bone status in these patients.

Long‐term effects of growth hormone (GH) on bone mineral status and bone turnover markers in patients with isolated GH deficiency and multiple pituitary hormone deficiency

This study was designed to assess the long-term effects of growth hormone (GH) replacement therapy on bone mass and bone turnover markers in children with isolated GH deficiency (IGHD) and multiple pituitary hormone deficiency (MPHD). Fifty children (35 IGHD, 15 MPHD) receiving GH replacement therapy were enrolled in the study. The patients were followed for 38.6 +/- 15.7 months (1-5 years). Bone mineral density (BMD) of the lumbar region and bone turnover markers [PTH, osteocalcin, bone-specific alkaline phosphatase (boneALP), and the carboxyterminal propeptide of type-1 collagen (CPP-I)] were assessed annually. The height standard deviation score (SDS) of patients with IGHD and MPHD at diagnosis was statistically significant (P = 0.012), and the change in height SDS during 3 years (Deltaheight SDS(3 years)) was statistically similar between these two groups (P = 0.651). The BMD z-scores of the two groups were comparable at the start of GH therapy (P = 0.083), and then increased in both groups similarly during 5 years of GH replacement therapy (F = 0.349, P = 0.567). When the BMD z-scores during 5 years of GH therapy were analysed in the IGHD and MPHD groups separately, it was found that the BMD z-score increased significantly in IGHD (P < 0.001) but the increase was not significant in MPHD (P = 0.140). Multiple regression analysis showed that the change in BMD z-score during 3 years of GH therapy (DeltaBMD z-score(3 years)) was predicted by the BMD z-score and height SDS at the start of GH therapy and by Deltaheight SDS(3 years) in the IGHD group (t = -2.582, P = 0.02; t = 2.322, P = 0.034 and t = 2.908, P = 0.01, respectively). Age and BMD z-score and height SDS at diagnosis were found to have predictive values for the DeltaBMD z-score(3 years) (t = -3.652, P = 0.022; t = -4.073, P = 0.015 and t = 3.389, P = 0.028, respectively) in the MPHD group. The changes in boneALP, osteocalcin, CPP-1 and PTH levels during the therapy were statistically similar between the IGHD and MPHD groups. BMD increased during GH therapy in the IGHD and MPHD groups. GH had a positive effect on bone mass in the short as well as the long term. Early diagnosis and treatment could improve peak bone mass in patients with MPHD. The time and dose of sex steroids for pubertal induction and progression, which mimics physiological secretion, might also contribute to bone accretion in patients with MPHD.

Bone Mineral Density and Alterations of Bone Metabolism in Children and Adolescents with Type 1 Diabetes Mellitus

To analysis bone mineral density (BMD) and bone turnover markers in children and adolescents with type 1 diabetes mellitus (DM1) and to establish possible correlations with duration of the disease and degree of metabolic control. Fifty-eight (26 prepubertal, 32 pubertal) children (29 boys) with DM1 (age: 11.7 +/- 3.1 years) and 44 (20 prepubertal, 24 pubertal) healthy children (21 boys) as controls (age: 10.8 +/- 3.2 years) were included in the study. BMD was measured by dual energy X-ray absorptiometry (DEXA). Scans of the lumbar spine (LS2-4) and femoral neck (FN) were carried out. Serum levels of osteocalcin, amino-terminal propeptide of type I procollagen (PINP), and alkaline phosphatase, as markers of bone formation, and urinary calcium/creatinine (Ca/Cr) ratio and levels of N-telopeptide (Ntx), as markers of bone resorption, were assessed. Anthropometrics, duration of DM1, presence of complications, insulin dose, and degree of metabolic control were obtained from the patients' records. In children with DM1 and controls, the mean measurements of LS2-4 BMD were 0.698 +/- 0.178 g/cm2 and 0.669 +/- 0.192 g/cm2, respectively (p >0.05), and FN-BMD measurements were 0.743 +/- 0.147 g/cm2 and 0.744 +/- 0.170 g/cm2, respectively (p >0.05). Children with DM1 had lower serum levels of calcium, intact parathyroid hormone, osteocalcin and PINP, and higher serum levels of 25-hydroxyvitamin D and urinary Ca/Cr (p <0.05). BMD was not related to any of the markers of bone resorption or formation, duration of the disease, or degree of metabolic control. Although we did not establish decreased LS2-4 and FN-BMD measurements in patients with DM1, we found reduced bone formation and increased bone resorption markers in children with DM1. Measurements of serum osteocalcin, PINP, urinary Ntx and Ca/Cr might be useful for long-term follow-up in children and adolescents with DM1.

Bone mineral density and bone turnover markers in children with chronic renal failure

Bone mineral density (BMD) at lumbar spine (L2-L4) was measured by dual-energy X-ray absorptiometry (DEXA) in 21 children with predialysis chronic renal failure (CRF) and 44 children with end-stage renal failure (ESRF) on regular hemodialysis. BMD results were expressed as Z-scores. Osteopenia was documented in 13 predialysis patients (61.9%) and 26 patients (59.1%) with ESRF. No significant correlation was observed between Z-scores and the duration of CRF or estimated creatinine clearance. In osteopenic children there was a negative correlation between Z-scores and serum phosphorus (r=-0.61, P=0.004), intact parathyroid hormone (iPTH) (r=-0.47, P=0.03), and bone-specific alkaline phosphatase (r=-0.52, P=0.02) and a positive correlation with total calcium (r=0.41, P=0.07) and 25-hydroxycholecalciferol (r=0.53, P=0.02). Osteopenic children who had iPTH values > or = 200 pg/ml were more osteopenic than those who had lower iPTH levels (P=0.006). In conclusion, osteopenia, assessed by DEXA, is frequent in children with CRF. It occurs early irrespective of the duration or the severity of CRF. In children with ESRF the degree of osteopenia is correlated with laboratory markers of renal osteodystrophy and patients with biochemical findings of secondary hyperparathyroidism are more osteopenic than the others.

Bone Mineral Density and Bone Turnover Markers in Children with Primary Nepherotic Syndrome

Bone Mineral Density and Bone Turnover Markers in Children with Primary Nepherotic Syndrome

Abnormalities of the PTH-vitamin D axis and bone turnover markers in children, adolescents and adults with cystic fibrosis: comparison with healthy controls.

Abnormalities of calcium and vitamin D metabolism in cystic fibrosis (CF) are well documented. We tested the hypothesis that alterations in calcium metabolism are related to vitamin D deficiency, and that bone resorption is increased relative to accretion in patients with CF. Calcitropic hormones, electrolytes, osteocalcin (OC) and bone alkaline phosphatase (BAP), (markers of bone mineralisation), urinary deoxypyridinoline [total (t) Dpd, a marker of bone resorption] and lumbar spine bone mineral density (LS BMD), expressed as a z-score, were measured in 149 (81 M) CF and 141 (61 M) control children aged 5.3-10.99 years, adolescents aged 11-17.99 years and adults aged 18-55.9 years. Data were analysed by multiple regression to adjust for age. In patients, FEV(1)% predicted and CRP (as disease severity markers), genotype and pancreatic status (PS) were recorded. The distribution of PTH differed between groups ( P<0.0001), with CF levels both below and above the control range. 25OH vitamin D (25OHD) was not different in control and CF subjects ( P=0.06). Active hormonal vitamin D (1,25(OH)(2)D) was lower in the CF group ( P<0.0001), not explained by 25OHD or disease severity, as was serum magnesium ( P<0.0001). OC was decreased in CF adults ( P=0.004), and tDpd increased in CF adolescents ( P=0.003) and adults ( P=0.03). The ratio of OC to tDpd (a measure of bone coupling) was similar in CF and control children, but decreased in CF adolescents ( P=0.04) and adults ( P=0.02), suggesting decreased overall bone accrual in CF adolescents and uncoupling of bone balance in adults. 1,25(OH)2D was weakly correlated with OC in CF children ( r=0.43, P=0.01), and with tDpd in CF and control adolescents ( r=0.33, P=0.05 and r=0.36, P=0.02, respectively); thus there was limited evidence of association of calcitropic hormones, which had an abnormal pattern in all age groups, with bone turnover. There was no association between calcitropic hormones or bone turnover markers and LS BMD z-score. Despite vitamin D sufficiency, abnormalities of calcium metabolism and bone turnover markers were still apparent and bone accretion was decreased relative to resorption in the CF adolescent and adult groups. These changes were not fully explained by disease severity or genotype, but are consistent with reports of decreased BMD and unique bone histomorphometry in older subjects with CF.

The effects of glucocorticoid replacement therapy on growth, bone mineral density, and bone turnover markers in children with congenital adrenal hyperplasia.

Even with current so called physiologic doses of glucocorticoid replacement therapy, children with congenital adrenal hyperplasia (CAH) often show relative short stature and delayed bone maturation, an observation that suggests possible long-term effects on bone metabolism of daily transient post-absorptive hypercortisolemia. In 28 patients with 21-hydroxylase or 17 alpha-hydroxylase deficiency (16 females and 12 males, ages 4.9-22 yr) who had received oral cortisol 10-15 mg/M2/day for 4.7-22 yr, we studied cortisol bioavailability, growth, bone maturation, vertebral bone mineral density, and various markers of bone formation and resorption. Patients were grouped according to mean on-therapy serum 170H-progesterone or progesterone levels as tight control (170HP < 10 nmol/L), fair control (170HP 10-40 nmol/L or progesterone 1.0-1.5 nmol/L), or poor control (170HP > 40 nmol/L). There was no difference in peak post-absorptive serum cortisol or area under the concentration-time curve, and only three patients had a peak serum cortisol of more than 700 nmol/L. There was no difference in present height Z-score (-0.96; -0.24; -0.6), height Z-score at age 2 yr (-1.5; +0.4; -1.3), or current growth velocity Z-score (-0.1; +1.2; -2.2) between the groups, but bone maturation Z-score was significantly delayed (-1.63) in the tight control group and advanced (+0.8) in the poor control group. Present height was highly correlated (r = 0.8) with height at age 2 yr. Serum calcium, phosphorus, alkaline phosphatase, parathormone, and 25OH-vitamin D levels were all normal. There was no difference between the groups in age-corrected vertebral bone mineral density, and no difference in serum osteocalcin, procollagen peptide, or collagen C-terminal telopeptide, nor in urinary amino-terminal telopeptide. The data suggest that current methods of cortisol replacement do not significantly influence bone formation, resorption or density during childhood and therefore should not contribute to adult osteoporosis. The possibility remains that hypercortisolemia during infancy produces the short stature and delayed bone maturation that are present by the age 2 yr.

The Effects of Glucocorticoid Replacement Therapy on Growth, Bone Mineral Density, and Bone Turnover Markers in Children with Congenital Adrenal Hyperplasia

Even with current so called physiologic doses of glucocorticoid replacement therapy, children with congenital adrenal hyperplasia (CAH) often show relative short stature and delayed bone maturation, an observation that suggests possible long-term effects on bone metabolism of daily transient post-absorptive hypercortisolemia. In 28 patients with 21-hydroxylase or 17 α-hydroxylase deficiency (16 females and 12 males, ages 4.9–22 yr) who had received oral cortisol 10–15 mg/M2/day for 4.7–22 yr, we studied cortisol bioavailability, growth, bone maturation, vertebral bone mineral density, and various markers of bone formation and resorption. Patients were grouped according to mean on-therapy serum 170H-progesterone or progesterone levels as tight control (170HP < 10 nmol/L), fair control (170HP 10–40 nmol/L or progesterone 1.0–1.5 nmol/L), or poor control (170HP > 40 nmol/L). There was no difference in peak post-absorptive serum cortisol or area under the concentration-time curve, and only three patients had a peak serum cortisol of more than 700 nmol/L. There was no difference in present height Z-score (−0.96;− 0.24; −0.6), height Z-score at age 2 yr (−1.5; +0.4; −1.3), or current growth velocity Z-score (−0.1; +1.2; −2.2) between the groups, but bone maturation Z-score was significantly delayed (−1.63) in the tight control group and advanced (+0.8) in the poor control group. Present height was highly correlated (r = 0.8) with height at age 2 yr. Serum calcium, phosphorus, alkaline phosphatase, parathormone, and 25OH-vitamin D levels were all normal. There was no difference between the groups in age-corrected vertebral bone mineral density, and no difference in serum osteocalcin, procollagen peptide, or collagen C-terminal telopeptide, nor in urinary amino-terminal telopeptide. The data suggest that current methods of cortisol replacement do not significantly influence bone formation, resorption or density during childhood and therefore should not contribute to adult osteoporosis. The possibility remains that hypercortisolemia during infancy produces the short stature and delayed bone maturation that are present by the age 2 yr.