Risk Of Metabolic Bone Disease Research Articles

Interventions to Minimize the Risk of Metabolic Bone Disease of Prematurity among Neonates: A Scoping Review

Premature newborns face significant risks of reduced bone mineral content ensuing osteopenia which are more likely to occur in high-risk newborns, particularly preterms who are on corticosteroids or diuretics for an extended period or have neuromuscular issues. The methodology prescribed by Arksey and O’Malley was followed. Database searches using PubMed, Scopus, and PEDro were performed for original research published in English between 2011 and 2022. Nine studies have shown that there are few papers on the role of physical therapy in preventing osteopenia of prematurity among newborns. The ability of a newborn to perform functionally is improved by early identification and exercise exposure. This scoping review aims to identify relevant and reliable studies that discuss the use of physical therapy to treat preterm newborns as this will decrease the chances of future complications among children.

Bone health in children undergoing solid organ transplantation.

Pediatric solid organ transplant recipients are a unique and growing patient population who are at risk for metabolic bone disease both before and after transplantation. The odds of sustaining a fracture in adulthood are significantly higher if an individual has sustained at least one childhood fracture, therefore, close monitoring before and after transplant is essential. Emerging data in patients with chronic kidney disease mineral and bone disorder (CKD-MBD) and hepatic osteodystrophy highlights the role of fibroblast growth factor 23 in the pathogenesis of metabolic bone disease in these conditions. While dual X-ray absorptiometry (DXA) is the most widely used imaging modality for assessment of bone mass in children, quantitative computer tomography (QCT) is an emerging modality, especially for patients with glucocorticoid-induced osteoporosis. Solid organ transplantation improves organ function and quality of life; however, bone mineral density can decline following transplantation, particularly during the first three to six months. Immunosuppressive medications, including glucocorticoids, are a major contributing factor. Following transplant, treatment should be tailored to achieve mineral homeostasis, correct nutritional deficiencies, and improve physical conditioning. In summary, early identification and treatment of metabolic bone disease can improve the bone health status of pediatric transplant recipients as they enter adulthood. http://links.lww.com/MOP/A71.

Characterisation of parathyroid hormone concentration in extremely preterm or very low birthweight infants in routine clinical screening for metabolic bone disease: A service evaluation cohort study.

To characterise parathyroid hormone (PTH) concentrations in infants at high risk for metabolic bone disease, in order to assist clinical decisions around the use of PTH for screening. Infants born under 28 weeks' postmenstrual age or with birthweight under 1.5 kg in a tertiary neonatal unit in the UK were included. Clinical guidance was to assess PTH concentration in the first 3 weeks after birth. Clinical information was extracted from prospective records. Sixty-four infants had mean birth gestation of 26 weeks and birthweight of 882 g. Median PTH (sent on median day 18 of life) was 9.2 pmol/L (interquartile range 5.3-17 pmol/L). Sixty-seven per cent of infants had a PTH greater than 7 pmol/L. For 22% of the infants, raised PTH was not accompanied by abnormal phosphate or alkaline phosphatase. Eighty-nine per cent of infants tested were insufficient or deficient for 25-hydroxyvitamin D. Universal screening highlights the high frequency of high PTH in this high-risk population, implying a need for calcium supplementation. A considerable number of infants would not be identified as showing potential signs of metabolic bone disease if the assessment excludes the use of PTH. The high level of 25-hydroxyvitamin D deficiency may be a confounder.

Artificial Neural Network Modeling to Predict Neonatal Metabolic Bone Disease in the Prenatal and Postnatal Periods

Early recognition of metabolic bone disease (MBD) in infants is necessary but difficult; an appropriate tool to screen infants at risk of developing MBD is needed. To develop a predictive model for neonates at risk for MBD in the prenatal and postnatal periods and detect the pivotal exposed factors in each period. A diagnostic study was conducted from January 1, 2012, to December 31, 2021, in Shanghai, China. A total of 10 801 pregnant women (singleton pregnancy, followed up until 1 month after parturition) and their infants (n = 10 801) were included. An artificial neural network (ANN) framework was used to build 5 predictive models with different exposures from prenatal to postnatal periods. The receiver operating characteristic curve was used to evaluate the model performance. The importance of each feature was examined and ranked. Of the 10 801 Chinese women who participated in the study (mean [SD] age, 29.7 [3.9] years), 7104 (65.8%) were local residents, 1001 (9.3%) had uterine scarring, and 138 (1.3%) gave birth to an infant with MBD. Among the 5 ANN models, model 1 (significant prenatal and postnatal factors) showed the highest AUC of 0.981 (95% CI, 0.970-0.992), followed by model 5 (postnatal factors; AUC, 0.977; 95% CI, 0.966-0.988), model 4 (all prenatal factors; AUC, 0.850; 95% CI, 0.785-0.915), model 3 (gestational complications or comorbidities and medication use; AUC, 0.808; 95% CI, 0.726-0.891), and model 2 (maternal nutritional conditions; AUC, 0.647; 95% CI, 0.571-0.723). Birth weight, maternal age at pregnancy, and neonatal disorders (anemia, respiratory distress syndrome, and septicemia) were the most important model 1 characteristics for predicting infants at risk of MBD; among these characteristics, extremely low birth weight (importance, 50.5%) was the most powerful factor. The use of magnesium sulfate during pregnancy (model 4: importance, 21.2%) was the most significant predictor of MBD risk in the prenatal period. In this diagnostic study, ANN appeared to be a simple and efficient tool for identifying neonates at risk for MBD. Combining prenatal and postnatal factors or using postnatal exposures alone provided the most precise prediction. Extremely low birth weight was the most significant predictive factor, whereas magnesium sulfate use during pregnancy could be an important bellwether for MBD before delivery.

Increased risk of metabolic bone disease in preterms born to preeclamptic mothers: A Case-Control Study

Objective: To evaluate if there is an increased risk of metabolic bone disease associated with preeclampsia Methods: Preterm infants <32 weeks in gestation and <1500 gr at birth, who were born in our hospital, followed at least six weeks were enrolled. Metabolic bone disease cases were defined as elevated serum ALP concentration >500 IU/L and serum phosphate levels<4 mg/dl with radiological evidence of osteopenia. The control cases had serum ALP concentration ≤ 500 IU/L and serum phosphate levels >5.6 mg/dl. Maternal factors and clinical variables including postnatal drug use, presence of reduced physical activity, hypotiroidism, feeding intolerance and gastrointestinal patology were reviewed for anaylsis. Results: The final analysis included 126 infants with 46 cases and 80 controls. Logistic regression showed birth weight, feeding intolerance, GIS pathology and preeclampsia were associated with the development of MBD. After the data adjusted for birth weight, preeclampsia showed a association with metabolic bone disease in preterms. Conclusion: Our study identifies preeclampsia as a risk factor for MBD in premature infants. Individualized approach to postnatal nutritional support is warranted for infants born to mothers with severe preeclampsia.

Risk factors for metabolic bone disease of prematurity: A meta-analysis.

To investigate the risk factors for metabolic bone disease of prematurity (MBDP), and to provide a reference for the prevention of MBDP. The databases including China Biomedical Literature Service System, China National Knowledge Infrastructure, Wanfang Data, and Weipu Periodical Database, PubMed, Web of Science, Embase, Cochrane Library and other databases were searched for studies on the risk factors for MBDP published up to June 18, 2021. RevMan 5.3 and Stata 14.1 software were used to perform a Meta analysis. A total of 15 articles were included, including 13 case-control studies, 1 current investigation, and 1 retrospective cohort study. There were 1,435 cases in the case group and 2,057 cases in the control group, with a total sample size of 3,492 cases. Meta analysis showed that risk factors for MBDP include birth weight <1000g (OR = 6.62, 95%CI: 2.28-19.25), gestational age <32 weeks (OR = 2.73, 95%CI: 1.07-6.95), septicemia (OR = 2.53, 95%CI: 1.69-3.79), parenteral nutrition time (OR = 4.04, 95%CI: 1.72-9.49), cholestasis (OR = 3.50, 95%CI: 1.49-8.23), intrauterine growth retardation (OR = 6.89, 95%CI: 3.81-12.44), while the birth weight(OR = 0.44, 95%CI: 0.21-0.90) and gestational age (OR = 0.57, 95%CI: 0.44-0.73)are the protective factors of MBDP. Factors like birth weight <1000g, gestational age <32 weeks, septicemia, parenteral nutrition time, cholestasis, and intrauterine growth retardation may increase the risk of metabolic bone disease of prematurity.

The impact of donor breast milk on metabolic bone disease, postnatal growth, and neurodevelopmental outcomes at 18 months' corrected age.

Preterm infants are at risk for metabolic bone disease (MBD). Analysis of donor breast milk (DBM) shows lower levels of macronutrients compared with mother's own milk (MOM). The purpose of this study was to investigate the prevalence of MBD, rate of postnatal growth, and long-term neurodevelopmental outcomes in infants fed predominantly MOM vs DBM. Retrospective observational study of infants born <1500g and <32 weeks at New York University Langone Health or Bellevue Hospital from January 2014 to January 2018. Infants were divided into two groups: those who received >70% of feeds with either MOM or DBM by 34 weeks' corrected age (CA). MBD was assessed using alkaline phosphatase (AlkPO4) levels and radiographic findings. Data was also collected on growth, feeding tolerance, and long-term neurodevelopmental outcomes. A total of 210 infants were included (MOM =156 and DBM =54). The DBM group had higher AlkPO4 levels for the first 3 weeks of life (P < .01). Growth was similar between the groups, and both groups demonstrated catch-up growth after discharge. No difference was seen in feeding intolerance, incidence of necrotizing enterocolitis, or sepsis. The DBM group had lower cognitive (odds ratio [OR], 0.93 [0.88-0.98]; P < .01) and language (OR, 0.95 [0.90-0.99]; P < .01) scores at 18 months' CA. Infants fed predominantly DBM had elevated AlkPO4 levels suggestive of MBD but did not develop osteopenia. Despite appropriate growth and comparable short-term outcomes, infants fed DBM had lower cognitive and language scores at 18 months' CA.

Screening of Serum Alkaline Phosphatase and Phosphate Helps Early Detection of Metabolic Bone Disease in Extremely Low Birth Weight Infants.

Background: Extremely low birth weight (ELBW, <1,000 g) infants have a high risk of metabolic bone disease (MBD). Because of the late appearance of radiological signs, diagnosis of MBD in ELBW infants might be delayed, and its prevalence underestimated in this group of patients. This study adopted serial screening of serum alkaline phosphatase (ALP) and phosphate (P) of ELBW infants to determine whether such screening is helpful for the early detection of MBD.Materials and Methods: We performed a retrospective study of preterm infants with a gestational age ≤ 31 weeks and birth weight <1,000 g. MBD was absent (ALP ≤500 IU/L), mild (ALP >500 IU/L, P ≥4.5 mg/dL), and severe (ALP >500 IU/L, P <4.5 mg/dL); MBD was divided into early MBD (≤4 weeks after birth) and late MBD (>4 weeks after birth) according to the time of onset.Results: A total of 142 ELBW infants were included, with a median gestational age of 28.1 (26.5–29.7) weeks and a median birth weight of 875 (818–950) g. Seventy-three cases of MBD were diagnosed, and the total prevalence was 51.4% (mild MBD, 10.6%; and severe MBD, 40.8%). Male sex, breastfeeding, and sepsis would increase the risk of severe MBD. Most MBD in ELBW infants occurred at 3–4 weeks after birth. Sixty-two percent (45/73) of infants were diagnosed as having early MBD, which are diagnosed earlier than late MBD [24 (21–26) vs. 39 (36–41), t = −7.161; P < 0.001]. Male sex [odds ratio (OR), 2.86; 95% confidence interval (CI), 1.07–7.64; P = 0.036], initial high ALP levels (OR, 1.02; 95% CI, 1.01–1.03; P < 0.001), and breastfeeding (OR, 5.97; 95% CI, 1.01–25.12; P = 0.049) are independent risk factors for the development of early MBD.Conclusion: The risk of MBD among ELBW infants is very high. Most cases occurred early and were severe. Male sex, initial high ALP levels, and breastfeeding are closely related to the increased risk of early MBD. Serial screening of serum ALP and P helps early detection of MBD; it is recommended to start biochemical screening for ELBW infants 2 weeks after birth and monitor their biochemical markers weekly.

SAT-405 CORRELATION OF SERUM CALCIUM, INORGANIC PHOSPHATE, ALKALINE PHOSPHATASE AND PARATHORMONE WITH BONE MINERAL DENSITY IN CHILDREN WITH RELAPSING NEPHROTIC SYNDROME

Children with relapsing (frequent relapse,FR and infrequent relapse,IFR) nephrotic syndrome (NS) are prone to develop low bone mineral density (BMD) due to disease process and or drugs. But the correlation of BMD with metabolic factors like, calcium (Ca). inorganic phosphate (IP), alkaline phosphatase (ALP) and parathormone are not very clear in these patients. So, the study was conducted to evaluate correlation of metabolic factors with BMD in children with relapsing NS. Cross sectional analytical study was carried out on 30 children: 21 frequent relapsers (FR; Group I), and 9 infrequent relapsers (IFR; Group II) undergo follow up in the pediatric nephrology unit of Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh, during the period from December, 2014 to November, 2015. Children between 5 to 15 years who fulfilled ISKDC criteria for diagnosis of NS with normal renal function and who were on alternate days steroid therapy were the participants of this study and children with abnormal renal function or who received cyclosporine or calcium supplement, or who had clinical evidence of any systemic illness were excluded from the study. All of the participants were subject to complete history taking, thorough clinical examination, laboratory investigations [serum creatinine, phosphorus (P), calcium (Ca), parathyroid hormone [PTH], and alkaline phosphatase (ALP)]. Bone mineral density was measured at the lumbar spinal region (L2-L4) using dual-energy X-ray absorptiometry (DXA). Mean age of the sample was 7.73±2.90 years while male to female ratio was 22/8. Serum Ca was lower while, serum P, ALP, and PTH were higher in Group I than that of Group II though difference was statistically insignificant (P= 0.3516). In group I, children had significantly lower Z-scores in BMD values (-2.70±1.28) compared to Group II (-1.30±1.54) and P value was significant (P=0.0317). Osteopenia was documented by DXA scan in 27% and osteoporosis in 53% and 20% patients were normal. On multivariate analysis, total dose of prednisolone (P=0.03693), serum calcium (P=0.03608), and phosphorus (P=0.04314) had linear relationship with dependent variable BMD Z-score. On univariate regression analysis, inverse relationship were observed between Parathormone (P =0.049) and serum Alkaline Phosphatase Level (P=0.00) with BMD Z Score. It can be inferred that, children with relapsing nephrotic syndrome are at risk for Metabolic Bone Disease, especially those receiving higher doses of steroids. Regular BMD evaluation and appropriate therapeutic interventions are recommended for these children.

Some biochemical and radiological markers of bone mineral content in premature neonates

Background and aim Inadequate supplementation of calcium and phosphorus in preterm infants significantly increases the risk of reduction of bone mineral content. As birth weight and/or gestational age increase, metabolic bone disease prevalence decreases and vice versa. This study aims to investigate and evaluate biochemical and radiological markers as early predictors of bone mineral content in preterm infants of up to 4 months of age. Patients and methods A case–control study included 20 preterm infants born less than 37 weeks of last menstrual period and 20 full term infants born greater than 37 weeks are involved as a full term group. Both groups are presented to the Neonatology Department, Al-Azhar University, Assuit, Egypt. Full history, full clinical examination, and investigations were done: complete blood count, serum alkaline phosphatase (ALP), serum total calcium (Ca), serum phosphorus (P), and wrist radiograph. Results According to investigations, there was no significant difference between preterm and full term infants in serum calcium and serum ALP at birth (P>0.05 for each), while there was significant difference between preterm and full term infants according to serum phosphorus, as the mean serum phosphorus in the preterm group (1.06±0.21) was lower than the mean serum phosphorus in the full term group (2.16±0.19) (P 0.05). Also, cases with rickets increase after 4 months in the preterm group (P Conclusion Metabolic bone disease in preterm infants is affected by gestational age and birth weight. As birth weight and/or gestational age increase, metabolic bone disease prevalence decreases and vice versa. Assessment of serum ALP and serum phosphorus have helped to identify and expect preterm infants with high risk of metabolic bone disease.

Clinical high-risk factors of metabolic bone disease in very low birth weight infants

Objective To explore the high-risk factors of metabolic bone disease(MBD)in premature infants by retrospective analysis of the clinical data so as to provide evidence for optimal clinical management. Methods Clinical data of premature infants with birth weight 500 IU/L and blood phosphorus <1.5 mmol/L were selected as MBD group and premature infants with birth weight <1 500 g were selected randomly as non-MBD group. General data, pulmonary surfactant, continuous positive airway pressure, mechanical ventilation, start time of enteral nutrition, parenteral nutrition (PN) time, breast feeding time and breast milk fortifier adding, drug usage, hospitalization time and complications were recorded and compared between the two groups. Results A total of 440 premature infants with birth weight <1 500 g were admitted to the hospital during the study period. 58[13.2%(58/440)] infants were enrolled in the MBD group, among which infants with birth weight <1 000 g accounting for 56.9%(33/58). High birth weight (OR=0.62, 95% CI: 0.389-0.990) was an independent protective factor of MBD in premature infants. The higher the birth weight, the lower the risk of MBD in premature infants. The longer duration of breast feeding time(OR= 2.191, 95% CI: 1.628-2.950), later initial time of enteral feeding(OR=2.695, 95% CI: 1.710-4.248), longer duration of PN(OR=6.205, 95% CI: 3.359-11.463) time, longer duration of respiratory supporting time(OR=1.046, 95% CI: 1.026-.067), longer hospital stay time(OR=1.703, 95% CI: 1.109-2.615) and small for gestational age(OR=2.965, 95% CI: 1.163-5.658) were independent risk factors of MBD in premature infants. The duration of PN was the most important independent risk factor of MBD in premature infants(OR=6.205, 95% CI: 3.359-11.463). Conclusion Multiple factors can lead to MBD of premature infants. The high birth weight is an independent protective factor of MBD and the duration of PN is the most important independent risk factor of MBD in premature infants. Key words: Premature infant; Metabolic bone disease; High risk factor

115 Bone Health in Chronic Pancreatitis: A Pilot Study

INTRODUCTION: Metabolic bone disease is associated with increased morbidity, mortality, and resultant health care costs. Chronic pancreatitis (CP) has multiple overlapping risk factors and complications (smoking, vitamin D malabsorption, fat maldigestion, alcohol abuse, and chronic inflammation) that promote an imbalance in bone mineralization and remodeling. This, in turn, leads to an increased risk of osteoporosis and fragility fractures. In this pilot study, we sought to assess the distribution of bone mineral density (BMD) and the clinical factors associated with reduced BMD in CP. METHODS: We selected patients with a definitive diagnosis of CP (according to the American Pancreatic Association guidelines) who were enrolled into The Ohio State Wexner Medical Center Pancreas Disease Biobank. Demographic and clinical details were abstracted, including age, sex, race, BMI, smoking, and alcohol history, and compared to BMD assessed by DEXA scans. RESULTS: Sixty-four patients with definite CP were identified. A total of 32 (50%) had bone mineral density screening with DEXA scans completed. Of those with BMD assessment, 59.3% (19/32) had a Z-score &lt; −1.5. The overall mean of the lowest DEXA Z-score for the CP cohort was −1.39. Of the CP patients with metabolic bone disease, the majority were older than 50 years of age (68%), and there was an equal distribution of males (59%) to females (60%). The mean Z-score was lower for females than males, although this did not reach statistical significance (−1.9 versus −1.3 respectively; P = 0.25). There was no association with bone disease and race, smoking and alcohol. CONCLUSION: Despite the increased risk of metabolic bone disease, only 50% of patients with CP had screening DEXA scans. Of these, metabolic bone disease was seen in up to 60% of CP patients. Older patients and female-gender had similar bone mineral density trends in CP as expected in the general population. A larger sample size of CP patients is needed to evaluate the true impact and predictors of metabolic bone disease in CP.

SUN-540 No Effect Of Alcohol Use On Bone Microarchitecture Of The Distal Radius Among HIV Infected Adults

The effect of alcohol consumption on cortical and trabecular microarchitecture is not well-understood particularly among patients living with HIV who are at higher risk for metabolic bone disease, osteopenia, and osteoporosis. The aim of this study was to assess the effect of heavy alcohol consumption on bone microarchitecture as measured by high-resolution peripheral quantitative computed tomography compared to low or no alcohol consumption among HIV-infected adults. We hypothesized that heavy alcohol consumption would have a detrimental impact on bone microarchitecture in both the cortical and trabecular compartments at the distal radius. We conducted a cross-sectional analysis among 238 participants (148 men, 42 pre-menopausal women, 48 post-menopausal women). Alcohol consumption status was based on the last 30 days (TimeLine Followback) and categorized into 4 categories based on the distribution in the study population: abstinence (0 grams(g)/day(d)) (n=82), lowest tertile (0.47 -7.0 g/d) (n=53), middle tertile (>7.0 - <35.0 g/d) (n=51), and highest tertile (35.0 - 454.1 g/d) (n=52). Bone microarchitecture measures included total volumetric bone mineral density (D100); Trabecular bone mineral density (Tb.BMD); Cortical bone mineral density (Ct.BMD); Trabecular number (Tb.N); Trabecular thickness (Tb.Th); Trabecular separation (Tb.Sp); Cortical thickness (Ct.Th); Cortical area (Ct.Ar). Associations between alcohol intake and bone microarchitecture measures were assessed using unadjusted and adjusted linear regression models. Covariates included sex, age, race, daily calcium intake, weight bearing physical activity, HIV viral load, number of years since first started taking antiretroviral therapy, intact reactive parathyroid hormone (iPTH), body mass index and number of years of heroin use. Among the density parameters, D100 was similar across all alcohol intake levels (adjusted p=0.75). The mean Tb.BMD was lowest among those who consumed low levels of alcohol (150.6 ± 41.5 mg HA/cm3) and highest among those who drank the heaviest (166.6 ± 48.6 mg HA/cm3). Mean Ct.BMD was highest with abstinence (854.8 ± 73.5 mg HA/cm3) followed by the lowest alcohol tertile (853.5 ± 60.5 mg HA/cm3) and then those reporting the heaviest drinking (829.4 ± 88.8 mg HA/cm3). However, the adjusted regression models showed no significant differences (p=0.94 and p=0.21, respectively) and remained non-significant after adjusting for 25-hydroxyvitamin D. There were no significant differences in the mean trabecular or cortical structural parameters including Tb.N (p=0.85), Tb.Th (p=0.90), Tb.Sp (p=0.73), Ct.Th (p=0.71), Ct.Ar (p=0.93) by alcohol intake after adjusting for covariates. We conclude that in this study population, bone microarchitecture measures did not differ by alcohol consumption status at the distal radius.

Status of Metabolic Bone Disease in Pediatric Steroid Resistant Nephrotic Syndrome: Study from North India

Background: Children with steroid resistant nephrotic syndrome (SRNS) are at a greater risk of metabolic bone disease due to biochemical derangements by corticosteroids and immunosuppressant therapy. The present study was undertaken to evaluate the calcium-vitamin D status in children with SRNS. Method: A cross-sectional case control study was performed to investigate the calcium-vitamin D status in 50 patients of SRNS and 40 healthy controls. Serum levels of 25 hydroxy vitamin D [25(OH) D], calcium, phosphorus, alkaline phosphatase (ALP) and parathyroid hormone (PTH) were estimated. The SRNS patients were further divided into 3 groups according to their Up:Uc ratio: Group A) 16 patients in complete remission, Group B) 14 patients in partial remission and Group C) 20 patients in relapse. Results: Vitamin D and calcium levels were significantly lower in the SRNS patients (p<0.0001). Lower levels of vitamin D and calcium were found in the relapse phase (p<0.01 and p=0.001). PTH and ALP levels were higher (p<0.05 and p=0.001). Up:Uc ratio with vitamin D and calcium showed a significant negative correlation (p<0.01 and p<0.05) whereas a positive correlation was seen with PTH and ALP ( p<0.05 for both). Conclusion: There is a clear diminution of serum 25 (OH) D in patients with SRNS which reverts rapidly to normal after cessation of proteinuria which may associate with severe nephrotoxicity. Prophylactic therapy with vitamin D should be routinely advocated in these patients.

Growth and Bone Mineralization of Very Preterm Infants at Term Corrected Age in Relation to Different Nutritional Intakes in the Early Postnatal Period.

Preterm infants often have a reduced bone mineral content (BMC) with increased risk of metabolic bone disease. After birth it is difficult to supply calcium (Ca) and phosphorus (P) comparable to the high fetal accretion rate. It is not known whether high supplementation of minerals in the early postnatal period improves growth and bone mineralization. The aim of this study was to evaluate growth and bone mineralization at term corrected age (TCA) in very and extremely preterm infants who received different enteral Ca and P intakes during the first 10 days of life. Infants (n = 109) with birth weights below 1500 g were randomly assigned to one of three groups that differed in the nutritional protocols delivered until day 10: Group A, mother’s own milk (MOM) and donor milk (unfortified); Group B, MOM (unfortified) and preterm formula; Group C, MOM (start fortification >50 mL/day) and preterm formula. Due to the earlier commencement of fortification, Group C received higher intakes of calcium and phosphorus and protein (p < 0.001) until day 10. At TCA weight, length, BMC and bone mineral density (BMD), measured by dual-X-ray absorptiometry, were not different between the groups. Nutritional intake of P was positively associated with length (β; (95% confidence interval (CI): 0.20 (0.001; 0.393); p-value = 0.048), whereas Ca intake was negatively associated with BMC (−1.94 (−2.78; −1.09); p-value < 0.001). A small interaction between Ca and P intake was only found for BMD (0.003 (0.00002; 0.00006); p-value = 0.036). The volume of human milk per kg provided during the first 10 days was positively associated with BMC (β; (95% CI): 0.013 (0.002; 0.023); p < 0.017). Higher intakes of Ca and P during the first 10 days, as provided in this study, did not improve bone mineralization at term corrected age.

Osteocalcin Level in Children with Steroid Dependent/Frequently Relapsing and Steroid Resistant Nephrotic Syndrome

Background: Children with nephrotic syndrome (NS) may be at risk for metabolic bone disease because of biochemical derangement caused by renal disease as well as steroid therapy. Osteocalcin (OC) functions as an inhibitor of bone mineralization. We aimed to evaluate linear growth and bone turnover markers (including serum osteocalcin) in children with steroid-dependant/frequently-relapsing and steroid resistant NS in comparison to a matched control group. Methods: Our study was a cross-sectional study conducted at children’s hospital, Cairo University, Egypt from July 2014 to August 2015. The study included 60 patients, aged 2 - 15 years recruited from outpatient nephrology clinic. Twenty eight age- and sex- matched healthy children were included as a control group. Serum OC was measured by immune-radiometric assay. Results: Serum OC levels were significantly higher in both SDNS/FRNS and SRNS than in control group, with P value 0.02 and 0.01, respectively. There was statistically significant negative correlation between OC and serum calcium. There was a negative correlation between height for age percentile and number of relapses. There were also negative correlations between height for age percentile and steroids, cyclophosphamide and cyclosporine duration of treatment. We found that both of our patients groups (SDNS/FRNS and SRNS) showed lower height for age percentile compared to control group (P = 0.017 and 0.001 respectively). Conclusions: Height as a growth parameter is more affected when recurrent relapses occur with multiple courses of steroid therapy. Use of OC as screening tool is recommended for bone turnover while patients on steroids.

Risk factors of metabolic bone disease of prematurity

ObjectiveTo identify the factors that increase risk of metabolic bone disease of prematurity (MBD). Study designA retrospective case-control study of infants born between January 2013–April 2014 with gestation age <30weeks and birth weight <1000g. MBD was defined as serum alkaline phosphatase above 500U/L and characteristic radiographic changes. Information was obtained on the presence of specific comorbidities. ResultsOf 76 infants evaluated, 40 met criteria for MBD. Median gestational age was 25weeks in both groups (p=0.512). Median birth weight of infants with MBD was significantly lower than that of controls (560 vs. 765g, p<0.01). Longer period of parenteral nutrition and dexamethasone use was observed in MBD group. Cholestasis was associated with the highest likelihood of MBD (OR 16.6, 95% CI 4.8–56.9). Seizures (OR 5.2, 95% CI 1.3–20.5) and the prolonged use of diuretics (OR 2.6, 95% CI 1.0–7.0) also significantly increased the likelihood of MBD. Only cholestasis remained significant (OR 9.6, 95% CI 2.1–45.3) after multiple regression analysis. ConclusionCholestasis is a significant risk factor for the development of MBD. Our future studies will be directed towards determining the causal relationship between cholestasis and MBD.

100 years of weight loss surgery: Voluntary weight loss, involuntary bone loss

In the past 100 years, there have been myriad medical discoveries—giant steps—from Louis Pasteur’s germ theory, to the understanding of gut physiology and metabolic processes—that are the essential underpinnings of modern day medicine. The beginnings of surgery to promote weight loss, now known as bariatric surgery, date back to the 1880s when it was noted that gut resections resulted in weight loss. It was not long afterward that articles started to appear documenting nutritional “disturbances” and the patient’s likelihood of survival based upon the location and the length of bowel removed. Numerous articles have been penned citing the first bariatric surgeries, but to date, there has not been a comprehensive look back at the origins of the science as well as the severe metabolic complications that furthered understanding, prompted innovative medical and surgical approaches, and ultimately led to modern day practice. This article endeavors to do exactly that. Intestinal bypass surgeries to treat obesity are here to stay. Some of the most profound complications of intestinal bypass manifest in the skeleton and include skeletal demineralization, hyperoxaluria, nephrolithiasis, and fractures. Much has been done to further elucidate the underlying mechanisms, identify preventive strategies, and implement practice guidelines, but this patient population remains at increased risk for metabolic bone disease.

Vitamins and functional nutrients for extremely low birth weight infants

While the need for appropriate post natalgrowth provides many studies focused on macronutrients in the nutrition of preterm infants, the concern for the quality of development of micro premies increases the interest in micronutrients, vitamins and trace elements. Moreover, the ongoing challenge to avoid serious complications of extreme prematurity requires investigations on functional nutrients especially those with antioxidant effect or immunomodulatory properties. Despite the lack of defined recommendations, much evidence is available. The antioxidant properties of vitamin A and vitamin E make these elements important in the nutrition of ELBW infants who are born with a strong deficit of these vitamins. Low plasma vitamin A concentrations increases the risk of chronic lung disease and long-term respiratory disabilities in preterm infants. Vitamin E counteracts peroxidation of polyunsaturated fattyacids in lipid layers of cell membranes[1]. Preterm infants are exposed to a special risk for metabolic bone disease also due to maternal deficiency and difficulty achieving adequate enteral intake of calcium, phosphorus, and vitamin D. The link between vitamin D supplementation, serum 25-OH-D concentration and long term outcome inpreterminfants are poorly understood. Some findings supportthe opinion that a vitamin D intake of 800-1000 IU/day is necessary in preterm infants while higher doses are needed in newbornof mothers with vitamin D deficiency [2]. Furthermore, vitamin D plays a rolein physiological processes that affect neuromuscular and immune functions, heart, lung, pancreas, and brain. Many trials reported enhanced visual acuity and better cognitive performance in the short-term assessments of preterm infants fed formulas supplemented with long chain polyunsaturated fattyacids(LCPUFA) [3-5]. However, there are many questions about the appropriate dosages and some doubts on the long-term advantages [6,7]. Among strategies for the prevention of NEC and sepsis through the use of immunonutrients, lactoferrin[8] and probiotics[9] are getting a place in clinical practice. Other studies will be needed to assess the extension of the evidence currently observed, especially for neonatesin low NEC rates settings. To date are available only weak evidence about the efficacy of arginine and glutamineto prevent intestinal mucosal injury in high risk infants [10]. Lutein supplementation for preterm infants raises plasma concentrations to those observed in human milk fed term infants and ensures the benefit of anti oxidant effect of carotenoidson immature retina and developing brain. Larger trials are needed to determine the best methods of administration to affect the retinopathy of prematurity[11].

Fractures Related to Metabolic Bone Disease in Children with Congenital Heart Disease.

Critically ill children with congenital heart disease (CHD) are at risk for metabolic bone disease (MBD) and bone fractures. Our objective was to characterize a cohort of CHD patients with fractures and describe a Fragile Bone Protocol (FBP) developed to reduce fractures. Patients who developed fractures in the Cardiac Intensive Care Unit (CICU) of Boston Children's Hospital from 3/2008 to 6/2014 were identified via quality improvement and radiology databases. The FBP (initiated July 2011) systematically identifies patients at risk for MBD and prescribes special handling precautions. Twenty-three fractures were identified in 15 children. Median age at fracture identification was 6.2 months, with a median duration of hospitalization before fracture diagnosis of 2.7 months. Six patients (40%) had single ventricle CHD. Hyperparathyroidism and low 25-OH vitamin D levels were present in 77% and 40% of those tested, respectively. Compared with patients not diagnosed with fractures, fracture patients had increased exposure to possible risk factors for MBD and had elevated parathyroid and decreased calcitriol levels.Six patients (40%) did not survive to hospital discharge, compared with an overall CICU mortality rate of 2.6% (P < .01). The fracture case rate before implementation of the FBP was 2.6 cases/1000 admissions and was 0.7/1000 after implementation of the FBP (P = .04). Critically ill CHD patients are at risk for fractures. They represent a complex group who frequently has hyperparathyroidism and decreased calcitriol levels, and each may predispose to fractures. FBPs consisting of identification and careful patient handling should be considered in at-risk patients.