Bone Turnover In Children Research Articles

Static histomorphometry parameters can identify bone turnover status in children and adults with chronic kidney disease

IntroductionTetracycline labeling for bone biopsy facilitates quantification of the pace of new bone production. As tetracycline labeling needs to be done prior to biopsy, it cannot be used to assess bone turnover in patients presenting with fractures, yet knowing turnover rate in patients experiencing fractures - especially in those with chronic kidney disease (CKD) - may guide appropriate medical therapy after surgical repair. Therefore, we sought to determine the diagnostic accuracy of static markers of bone turnover relative to tetracycline labeling in a pediatric and adult cohort of patients with chronic kidney disease (CKD) undergoing iliac crest biopsy with histomorphometry. MethodsWe evaluated two cohorts, one of 147 children and young adults ages 18±10 and another of 151 adults ages 49±13 who had undergone iliac crest biopsy with tetracycline labeling for clinical indications of CKD-mineral and bone disorders. We used bone formation rate relative to bone surface (BFR/BS) based on double tetracycline labeling as our gold standard marker of bone turnover. A blinded investigator used light microscopy without fluorescence to measure static bone turnover parameters. We compared the area under the ROC curve (AUC), sensitivity, and specificity of each static parameter with low and high bone turnover based on BFR/BS. ResultsIn the pediatric and adult cohorts, 35 (24 %) and 70 (46 %) had low bone turnover, respectively, and 18 (12 %) and 30 (20 %) had high bone turnover, respectively. The static parameters with the greatest AUCs for low and high turnover were osteoblasts surface/bone surface (Ob.S/BS), osteoclasts surface/bone surface (Oc.S/BS), eroded surface/bone surface (ES/BS), osteoid surface/bone surface (OS/BS), osteoid volume/bone volume (OV/BV), and osteoid thickness (O.Th.) in both cohorts. Ob.S/BS had the highest AUC for low and high turnover in the pediatric cohort (0.8204 and 0.8678, respectively) whereas Oc.S/BS had the highest AUC for low turnover (0.8325) and ES/BS had the highest AUC for high turnover (0.7360) in the adult cohort. DiscussionStatic measures of histomorphometry that do not rely on tetracycline bone labeling can identify low and high bone turnover in children and adults with CKD with moderate to high accuracy. This approach may allow assessment of bone turnover in the setting of clinical fractures where clinicians may have access to bone tissue but where tetracycline labeling is not possible.

Evaluation of bone mineral density and bone turnover in children on anticoagulation.

Childhood and adolescence are critical periods of bone mineral acquisition. Children on anticoagulation (AC) might have an increased risk for reduced bone mineral density (BMD). Risk factors for impaired bone accumulation include chronic diseases, immobility, and medication. Vitamin K (VK) deficiency reflected by undercarboxylated osteocalcin levels (ucOC) has been identified as a predictor of osteoporosis and fractures. Data on bone health in children under AC are sparse. To evaluate BMD in children on AC and characterize the risk factors of low BMD, including VK and Vitamin D (VD) status. Single-center cross-sectional study of clinical, biochemical, and densitometric parameters. Assessment of VK surrogate parameters included ucOC and matrix gla protein (MGP). A total of 39 children (4-18 years; 12 females) receiving AC were included, 31 (79%) on VK antagonists and 8 (21%) on direct oral anticoagulants. Overall, BMD was decreased for both the lumbar spine (LS; -0.7SDS) and total body less head (TBLH; -1.32SDS) compared with pediatric reference data. Significant associations were found between early pubertal development and TBLH-BMD, and between BMI and LS-BMD. VK surrogate parameters were highly related to patients' age and pubertal development. Neither serum parameters nor AC-related factors predicted BMD. VD was detected in 10/39 patients with lower values during puberty. Our data indicate BMD reduction in pediatric patients on AC. Although AC-related factors did not predict reduced BMD, low BMI and pubertal stages represented important risk factors. Awareness of risk factors for low BMD and high prevalence of VD deficiency during puberty could contribute to the improvement of bone health in this vulnerable patient group.

Investigation of the relationship between serum sclerostin and dickkopf-1 protein levels with bone turnover in children and adolescents with type-1 diabetes mellitus

Diabetes mellitus (DM) is widely known to have a detrimental effect on bone health and is associated with increased fracture risk. Recently, the Wnt/beta-catenin signaling pathway and its inhibitors sclerostin and dickkopf-1 (Dkk-1) were found to be involved in the control of bone mass. The present study aimed to measure serum sclerostin and Dkk-1 protein levels in children and adolescents with type-1 DM and compare with other bone turnover markers and bone mineral density (BMD). This study was performed on 40 children and adolescents with type-I DM and 40 healthy children and adolescents. Anthropometric measurements and pubertal examination were done. In addition to laboratory analysis, dickkopf-1, sclerostin, cross-linked N-telopeptides of type I collagen (NTx), bone alkaline phosphatase (bALP), and osteocalcin levels were studied. BMD of the participants was measured by calcaneus ultrasonography. Dickkopf-1 levels of the children and adolescents with type-1 DM were significantly higher, vitamin D, NTx, osteocalcin, and phosphorus levels were significantly lower than those of the controls (p<0.001). Fasting blood glucose, HbA1c, and insulin were significantly higher in the type 1 DM group (p<0.01). Both bone remodeling and its compensatory mechanism bone loss are lower in children and adolescents with type-1 DM than in the controls. Also, higher levels of Dkk-1 play a role in decreased bone turnover in these patients. Since Dkk-1 and sclerostin seem to take a role in treating metabolic bone diseases in the future, we believe that our findings are significant in this respective.

Nutritional Targets in Cow's Milk Protein Allergy: A Comprehensive Review.

Cow's milk protein allergy (CMPA) is known as the most common food allergy in the first year of life. For this purpose, in our review, the regulation of maternal and infant nutrition, and the risks and the issues to be considered in terms of nutrition are discussed from the perspective of a dietitian. Therefore, understanding the epidemiology, symptoms, diagnostic criteria, and appropriate treatment of cow's milk protein allergy is crucial for the multidisciplinary team of physicians, dietitians, and nurses working in the clinic. It has been reported that tolerance develops in approximately 50% of infants affected by cow's milk protein in the first year of life. Although CMPA is generally thought to clear up between 1 and 2years of age, there is insufficient evidence to determine an optimal time to reintroduce cow's milk protein to the diet. Because the elimination diet recommended in the treatment of children with CMPA, adequate protein and calcium intake of the mother and/or baby in the diet should be evaluated. Studies focusing on metabolic bone turnover in children with food allergies are limited. In general, low calcium intake is associated with reduced bone formation in children with CMPA. Therefore, bone health should be focused on and appropriate strategies should be developed in children with CMPA. Unnecessary elimination of milk and its products, which are an important part of nutrition, should be prevented and nutrient deficiencies and growth status should be monitored by dietitians especially working in the field of pediatric nutrition.

Low Serum 25-hydroxyvitamin D Level Does Not Adversely Affect Bone Turnover in Prepubertal Children.

Both vitamin D and insulin-like growth factor 1 (IGF-1) play essential roles in bone metabolism and may interact during prepubertal bone accrual. We investigated the association of low serum 25-hydroxyvitamin D (25(OH)D) (<20 ng/mL) with the circulating bone turnover markers, when compared to their interaction with IGF-1. Subjects and Methods: Serum 25(OH)D, IGF-I, P1NP (N-terminal propeptide of type I procollagen), and CTX-1 (C-terminal telopeptide of type I collagen) were measured, and the bone turnover index (BTI) was calculated in 128 healthy children, aged 9–11 years. Results: Mean 25(OH)D concentration was 21.9 ± 4.9 ng/mL, but in 30.5% of participants it was <20 ng/mL (<50 nmol/L). We observed a trend for higher P1NP (p < 0.05) and IGF-1 (p = 0.08), towards lower 25(OH)D in tertiles. Levels of P1NP in the lowest 25(OH)D tertile (<20 ng/mL) were the highest, while CTX and BTI remained unchanged. Additionally, 25(OH)D negatively correlated with IGF-1, while the correlation with P1NP was not significant. A strong positive correlation of IGF-1 with P1NP and BTI but weak with CTX was observed. Low 25(OH)D (<20 ng/mL) explained 15% of the IGF-1 variance and 6% of the P1NP variance. Conclusions: Low levels of 25(OH)D do not unfavorably alter bone turnover. It seems that serum 25(OH)D level may not be an adequate predictor of bone turnover in children.

Relationship between bone turnover markers and oxidative stress in children with type 1 diabetes mellitus.

Oxidative stress in children with type 1 DM (T1DM) may negatively affect the bone. This study included 40 children with T1DM as the patient group and 40 healthy childrenof matched age and sex as the control group. Plasma alkaline phosphatase, procollagen type-1 amino-terminal propeptide (P1NP), and urinary deoxypyridinoline (DPD) were measured to assess bone turnover. Glutathione, superoxide dismutase (SOD), and malondialdehyde (MDA) were measured to assess oxidative stress. Patients with T1DM had a significantly lower P1NP level but a significantly higher urinary DPD level compared to the control group. Moreover, there were significantly lower glutathione and SOD levels with significantly higher MDA levels in patients with T1DM. We found a significant positive correlation between P1NP level and both glutathione and SOD levels but a significant negative correlation between P1NP and MDA in patients with T1DM. There was a significant negative correlation between DPD levels and both glutathione and SOD levels and a significant positive correlation between DPD and MDA. Moreover, glutathione was a significant predictor for both P1NP and DPD levels, while MDA was a significant predictor for P1NP levels. There is an association between oxidative stress and bone turnover markers in children with T1DM. Oxidative stress can negatively affect bone but the exact relationship between oxidative stress and bone turnover in T1DM has not been previously studied in pediatrics. For the best of our knowledge, our study was the first to assess the relationship between oxidative stress and bone turnover in children with T1DM. We revealed that increased oxidative stress in children and adolescents with T1DM may be involved in the impairment of bone turnover process, so treatment strategies toward better glycemic control and decreasing oxidative stress may be beneficial in preventing and treating diabetic bone disease in these children.

Decreased markers of bone turnover in children and adolescents with type 1 diabetes.

Adults with type 1 diabetes (T1D) have increased risk of bone fractures and decreased bone mineral density (BMD). Alterations in bone turnover have been suggested as the link between T1D and the impaired bone health. Furthermore, bone turnover has been suggested to have beneficial effects on glucose metabolism. This study aimed at describing bone turnover markers (BTM), and the relationship with glycemic control, in children and adolescents with T1D. A total of 173 (47% girls) children and adolescents aged 7.7 to 17.5 years with T1D for more than 1 year were included. Participants were evaluated by BMD together with measurements of selected BTM; two formation markers: osteocalcin (OCN) and procollagen type-1 amino-terminal propeptide (P1NP) and one resorption marker, C-terminal cross-linked telopeptide of type-1 collagen (CTX). BTM were converted into Z-scores utilizing new national references. Mean OCN Z-score (-0.68 ± 1.31), P1NP Z-score (-0.33 ± 1.03) and CTX Z-score (-0.43 ± 1.10) were all significantly lower than the reference population (P < .001). No associations were seen between BTM and T1D duration. BMD Z-score was comparable to the reference population and associated with none of individual BTMs. CTX Z-score was negatively associated with HbA1c (P = .007) independent of both exogenous and residual endogenous insulin. Markers of bone formation and resorption were decreased in children and adolescents with T1D. CTX Z-score associated negatively with HbA1c adjusted for insulin treatment and endogenous insulin production indicating a potential association between CTX and insulin sensitivity. The long-term consequences of decreased BTM on BMD need further attention.

Bone turnover markers in children and adolescents with type 1 diabetes-A systematic review.

Type 1 diabetes (T1D) is associated with impaired bone health and both osteocalcin (OCN) and procollagen type 1 amino terminal propetide (P1NP) (markers of bone formation) and C-terminal cross-linked telopeptide (CTX) (marker of bone resorption) are decreased in adult patients with T1D. We review the existing literature characterizing these bone turnover markers in children and adolescents with T1D and by meta-analysis examine whether alterations in OCN, P1NP, and CTX are evident and if potential changes correlate to the metabolic control (hemoglobin A1c, HbA1c). Systematic searches at MEDLINE and EMBASE were conducted in January 2018 identifying all studies describing OCN, P1NP, or CTX in children and adolescents with T1D. A total of 26 studies were included, representing data from more than 1000 patients with T1D. Pooled analyses of standard mean difference and summary effects analysis were performed when sufficient data were available. Pooled analysis revealed mean OCN to be significantly lower in children and adolescents with T1D compared to healthy controls (standard mean difference: -1.87, 95% confidence interval, CI: -2.83; -0.91) whereas both P1NP and CTX did not differ from the controls. Only data on OCN was sufficient to make pooled correlation analysis revealing a negative correlation between OCN and HbA1c (-0.31 95% CI: -0.45; -0.16). In conclusion, OCN is decreased in children and adolescents with T1D, whether CTX and P1NP are affected as well is unclear, due to very limited data available. New and large studies including OCN, P1NP, and CTX (preferably as z-scores adjusting for age variability) is needed to further elucidate the status of bone turnover in children and adolescents with T1D.

Age-related changes in biochemical bone profile in thalassemic children

Osteopathy is an important cause of morbidity in β-thalassemia major (TM). Although many of the etiopathological factors implicated in thalassemic osteoporosis commence in early disease phases during childhood, limited information exists on bone turnover in children with TM. This study was conducted with the objective to compare bone turnover markers (BTMs) in thalassemic children at different ages. In a cross sectional case control study, 47 children (age range, 1.5-18 years) with TM were recruited. BTMs were compared to eighteen age- and sex-matched healthy controls and to 16 adults (age range, 19.67-31.08 years) with TM. Thalassemic children displayed unbalanced bone turnover with an increased bone resorption (shown by high levels of tartrate-resistant acid phosphatase 5b (TRACP5), receptor activator of nuclear factor-kappa B ligand (sRANKL) and sRANKL/osteoprotegerin (OPG) ratio) and a decreased bone neoformation (shown by low levels of osteocalcin (OC)) when compared to healthy children. TRACP5b was the only BTMs studied that showed a significant correlation with age in thalassemic children. For the whole thalassemic children group, regression analyses showed an influence of sex hormones replacement therapy on TRACP5b; pretransfusion hemoglobin and splenectomy on sRANKL; pretransfusion hemoglobin on sRANKL/OPG; and pretransfusion hemoglobin and serum ferritin on OC. The present study confirms that TM has profound effects on bone metabolism starting from early childhood. The early onset of bone turnover disturbances in TM indicates the need to investigate possible option to intervene early.

Congenital Hypothyroidism and Bone Remodeling Cycle.

Objective:The present study aimed to evaluate the biochemical markers of bone turnover in children with congenital hypothyroidism during the course of treatment as compared to healthy children selected as controls.Methods:The study included 31 children with congenital hypothyroidism and 29 healthy children. In both groups, we evaluated serum procollagen type-1 N-terminal propeptide (PINP) and tartrate-resistant acid phosphatase type 5b isoform (TRACP 5b) levels as bone turnover markers.Results:In both groups, thyroid hormone levels were within normal limits. The levels of vitamin D were significantly higher in the cases with congenital hypothyroidism. Although PINP levels were not found to be different, TRACP 5b levels which are related to osteoclastic activities were significantly higher in the control group.Conclusion:We did not detect an increase in bone resorption in patients with congenital hypothyroidism, despite long-term treatment with LT4. Our results suggest that with effective vitamin D treatment and thyroxin replacement, congenital hypothyroidism is not a deleterious factor for bone turnover.

Biochemical markers of bone turnover in children with clinical bone fragility.

The role of biochemical bone turnover markers (BTMs) in assessing low bone mass and monitoring bisphosphonate treatment in pediatric patients with clinical bone fragility is not well established. The aim of the study was to examine the correlations of BTMs and the bone mineral density (BMD), and evaluate the effects of bisphosphonates therapy on BTMs in children with clinical bone fragility. Clinical data of 115 patients with clinical bone fragility (mean age 9.7±5.8 years), 102 of whom received bisphosphonates, were studied. Serum alkaline phosphatase (ALP), osteocalcin (OC), urine pyridinoline (PD) and deoxypyridinoline (DPD), BMD at baseline and subsequent years were analyzed. There was a significant negative correlation between urine PD and lumbar BMD (slope=-0.29, p<0.001). There were no correlations between BTMs and lumbar BMD Z-score. There was a significant positive correlation between serum OC and serum ALP, urine PD and DPD (p<0.001). Serum OC, urine PD and DPD index, as expressed as measured value/upper limit of normal value for age, decreased during the first 3 years of bisphosphonate therapy. In children with clinical bone fragility, BTMs correlated with each other, but not with lumbar BMD Z-score. While they were not reliable predictors of degree of low BMD, the bone markers showed suppression during bisphosphonate therapy and may be helpful in monitoring the response to therapy.

Effect of vitamin D supplementation on glucose metabolism, immune function and bone turnover in children with vitamin D deficiency

Effect of vitamin D supplementation on glucose metabolism, immune function and bone turnover in children with vitamin D deficiency

Effect of vitamin D treatment on glucose and insulin metabolism, and bone turnover in children with symptomatic vitamin D deficiency

Effect of vitamin D treatment on glucose and insulin metabolism, and bone turnover in children with symptomatic vitamin D deficiency

Effects of Pump versus Twice-Daily Injection Delivery of Synthetic Parathyroid Hormone 1-34 in Children with Severe Congenital Hypoparathyroidism

To compare the response with synthetic human parathyroid hormone (PTH) 1-34 delivered by twice-daily injection vs insulin pump in children with severe congenital hypoparathyroidism due to calcium receptor mutation or autoimmune polyglandular syndrome type 1. Children and young adults aged 7-20 years with congenital hypoparathyroidism (N = 12) were randomized to receive PTH 1-34, delivered either by twice-daily subcutaneous injection or insulin pump for 13 weeks, followed by crossover to the opposite delivery method. The principal outcome measures were serum and urine calcium levels. Secondary outcomes included serum and urine magnesium and phosphate levels and bone turnover markers. PTH 1-34 delivered via pump produced near normalization of mean serum calcium (2.02 ± 0.05 [pump] vs 1.88 ± 0.03 [injection] mmol/L, P < .05, normal 2.05-2.5 mmol/L), normalized mean urine calcium excretion (5.17 ± 1.10 [pump] vs 6.67 ± 0.76 mmol/24 h/1.73 m(2), P = .3), and significantly reduced markers of bone turnover (P < .02). Serum and urine calcium and magnesium showed a biphasic pattern during twice-daily injection vs minimal fluctuation during pump delivery. The PTH 1-34 dosage was markedly reduced during pump delivery (0.32 ± 0.04 vs 0.85 ± 0.11 μg/kg/d, P < .001), and magnesium supplements were also reduced (P < .001). Compared with twice-daily delivery, pump delivery of PTH 1-34 provides more physiologic calcium homeostasis and bone turnover in children with severe congenital hypoparathyroidism.

Effects of dietary protein and glycaemic index on biomarkers of bone turnover in children

For decades, it has been debated whether high protein intake compromises bone mineralisation, but no long-term randomised trial has investigated this in children. In the family-based, randomised controlled trial DiOGenes (Diet, Obesity and Genes), we examined the effects of dietary protein and glycaemic index (GI) on biomarkers of bone turnover and height in children aged 5-18 years. In two study centres, families with overweight parents were randomly assigned to one of five ad libitum-energy, low-fat (25-30% energy (E%)) diets for 6 months: low protein/low GI; low protein/high GI; high protein/low GI; high protein/high GI; control. They received dietary instructions and were provided all foods for free. Children, who were eligible and willing to participate, were included in the study. In the present analyses, we included children with data on plasma osteocalcin or urinary N-terminal telopeptide of collagen type I (U-NTx) from baseline and at least one later visit (month 1 or month 6) (n 191 in total, n 67 with data on osteocalcin and n 180 with data on U-NTx). The level of osteocalcin was lower (29.1 ng/ml) in the high-protein/high-GI dietary group than in the low-protein/high-GI dietary group after 6 months of intervention (95% CI 2.2, 56.1 ng/ml, P=0.034). The dietary intervention did not affect U-NTx (P=0.96) or height (P=0.80). Baseline levels of U-NTx and osteocalcin correlated with changes in height at month 6 across the dietary groups (P<0.001 and P=0.001, respectively). The present study does not show any effect of increased protein intake on height or bone resorption in children. However, the difference in the change in the level of osteocalcin between the high-protein/high-GI group and the low-protein/high-GI group warrants further investigation and should be confirmed in other studies.

Skeletal effects and growth in children with chronic kidney disease: a 5-year prospective study

This study was designed to follow the evolving process of growth, bone modeling and remodeling in children with chronic kidney disease (CKD) who are at risk of developing CKD-mineral bone disorder (CKD-MBD). Fifteen patients, 4-15 years, were included with a median glomerular filtration rate of 46 (range 12-74) mL/min/1.73 m(2). Growth, bone mineral density (BMD) and markers of bone and mineral metabolism were investigated over a 5-year period. The median height standard deviation score was -0.65 at the start and 0.1 after 5 years, with a range from -1.7 to 1.7, which implies that growth was acceptable. Total body, femoral neck, and lumbar spine BMD increased over the study period (p < 0.0001). None had total body BMD Z-scores and lumbar spine Z-scores below -2.0 at follow-up. Most bone markers were within the reference intervals, but the formation markers of alkaline phosphatase and type I procollagen intact amino-terminal propeptide (PINP) were slightly increased in about one-third of the patients after 5 years. Eleven out of 15 CKD patients had increased parathyroid hormone levels at baseline and 10 patients after 5 years had increased parathyroid hormone levels. Taken together, this is the first 5-year longitudinal study of skeletal effects, growth and bone turnover in children with CKD. Growth and BMD Z-scores were well preserved on a group basis; however, these parameters varied significantly on an individual basis. We suggest, therefore, that it is difficult to state an overall recommendation and growth, bone mass, and markers of bone and mineral metabolism should be monitored and treated individually in CKD children.

Bone turnover is not influenced by serum 25-hydroxyvitamin D in pubertal healthy black and white children

Low serum 25-hydroxyvitamin D [25 (OH) D] is common in healthy children particularly in blacks. However, serum 25 (OH) D concentrations for optimal bone turnover in children is unknown and few data exist that describe effects of increasing serum 25 (OH) D on bone turnover markers during puberty. The purpose of this study was to determine the relationships between serum 25 (OH) D and changes in serum 25 (OH) D and bone turnover in white and black pubertal adolescents. Bone turnover markers were measured in 318 healthy boys and girls from Georgia (34°N) and Indiana (40°N) who participated in a study of oral vitamin D3 supplementation (0 to 4000IU/d). Serum 25 (OH) D, osteocalcin, bone alkaline phosphatase, and urine N-telopeptide cross-links were measured at baseline and 12weeks. Relationships among baseline 25 (OH) D and bone biomarkers, and between changes over 12weeks were determined and tested for effects of race, sex, latitude, and baseline 25 (OH) D. Median 25 (OH) D was 27.6ng/mL (n=318, range 10.1–46.0ng/mL) at baseline and 34.5ng/mL (n=302, range 9.7–95.1ng/mL) at 12weeks. Neither baseline nor change in 25 (OH) D over 12weeks was associated with bone turnover. The lack of association was not affected by race, sex, latitude, or baseline serum 25 (OH) D. Serum 25 (OH) D in the range of 10–46ng/mL appears to be sufficient for normal bone turnover in healthy black and white pubertal adolescents.

Bone mass and biochemical markers of bone turnover in children and adolescents with chronic immune thrombocytopenia: Relation to corticosteroid therapy and vitamin D receptor gene polymorphisms

Optional drug therapy in refractory chronic immune thrombocytopenia (ITP) includes standard oral, pulsed high-dose steroid therapy, intravenous gamma globulin, anti-D, and immunosuppressive therapy or thrombopoietin receptor agonists. This work aimed to study the bone mass in children and adolescents with chronic ITP in relation to biochemical markers of bone turnover, cumulative steroid therapy, and the possible modulating effect of vitamin D receptor (VDR) gene polymorphisms. Thirty-six children and adolescents with chronic ITP were recruited from the Hematology Clinic, Children's Hospital, Ain Shams University and the Hematology Clinic of the National Research Centre in Egypt and compared with 43 healthy age- and sex-matched controls. The total cumulative dose of steroids was calculated. Bone markers (serum osteocalcin (OC) and propeptide I precollagen (PICP) and urinary deoxypyridinoline (DPD) excretion), analysis of VDR gene distribution, and dual energy X-ray absorptiometry at lumbar and hip regions were performed for patients and controls. Compared to controls, chronic ITP patients had higher body mass index (BMI) and lower height for age standard deviation score (SDS). Chronic ITP patients had lower levels of OC and C-terminal propeptide of type I procollagen (PICP) and higher urinary DPD excretion, and bone mineral density (BMD) was significantly lower for both spine and hip z-score (<0.001). BMD was inversely correlated with urinary DPD excretion, age, BMI, and cumulative steroid dose. There was significant negative correlation between cumulative oral steroid dose and BMD (r = −0.4, P = 0.01 and r = −0.45, p = 0.001 for spine and hip z-scores, respectively), but the correlation was non-significant in relation to cumulative pulsed steroid therapy. FokI polymorphism was significantly related to BMD for both spine and hip z-score (p = 0.015 and p = 0.008, respectively), but there was no relation between BMD and Bsm1 polymorphism. FokI gene polymorphism may be one of the contributing factors in bone loss in patients on chronic steroid therapy. High cumulative doses of corticosteroids increased bone resorption in young chronic ITP patients. Longitudinal studies are needed to confirm the effect of different steroid protocols on bone turnover. Protocols of therapy of chronic ITP should restrict corticosteroid use in growing children and favor alternative less harmful therapies.

Early predictors of increased bone resorption in juvenile idiopathic arthritis: OPG/RANKL ratio, as a key regulator of bone metabolism

Aim(s) of the workTo explore early changes in the predictors of bone turnover in children with juvenile idiopathic arthritis (JIA). To identify osteoprotegerin/receptor activator of nuclear factor-κB ligand (OPG/RANKL) ratio in the serum of the same patients and its relation to the parameters of joint inflammation and joint destruction. Patients and methodsSeventy children with JIA and 30 healthy children individually matched for age, sex, race, and county of residence were included in this study. Serum levels of calcium (Ca), phosphorus (Ph), alkaline phosphatase (ALP), osteocalcin (OC), RANKL and (OPG) were measured. Urinary concentration of deoxypyridinoline (DPD) was also done. All involved joints were assessed by plain radiography. ResultsSignificant low serum concentrations of ALP and OPG was observed in JIA group, while there was a significant increase in serum level of RANKL and urine level of DPD compared to controls. OPG/RANKL ratio was significantly lower in JIA patients than in controls. OPG/RANKL ratio is correlated with most clinical characteristics, disease activity variables, JIA outcome measures and radiographic findings. DPD, RANKL and OPG/RANKL ratio, respectively, are considered as independent predictors of juxta-articular osteoporosis. OPG/RANKL ratio was the only predictor of bone erosion. ConclusionThe OPG/RANKL ratio could be an early predictor of increased bone resorption and a valuable biomarker for joint inflammation and bone injury in JIA patients.

Serum Osteocalcin, Zinc Nutritive Status and Bone Turnover in Children and Adolescents with Type1 Diabetes Mellitus

Serum Osteocalcin, Zinc Nutritive Status and Bone Turnover in Children and Adolescents with Type1 Diabetes Mellitus