Predictive Fat Mass Equations for Children With Inflammatory Bowel Disease.

OBJECTIVE: Evaluate accuracy of skinfold thicknesses and body mass index (BMI) for the prediction of fat mass percentage (FM%) in paediatric inflammatory bowel disease (IBD) and to develop population-specific formulae based on anthropometry for estimation of FM%. METHODS: IBD children (n = 30) and healthy controls (HCs, n = 144) underwent anthropometric evaluation and dual-energy X-ray absorptiometry (DEXA) scan, as the clinical reference for measurement of body composition. Body FM% estimated with skinfolds thickness was compared with FM% measured with DEXA. By means of 4 prediction models, population specific formulae for estimation of FM% were developed. RESULTS: No significant difference in terms of FM% measured by DEXA was found between IBD population and HCs (FM% 29.6% vs 32.2%, P = 0.108). Triceps skinfold thickness (TSF, Model 2) was better than BMI (Model 1) at predicting FM% (82% vs 68% of variance). The sum of 2 skinfolds (biceps + triceps; SF2, Model 3) showed an improvement in the prediction of FM% as compared with TSF, Model 2 (86% vs 82% of variance). The sum of 4 skinfolds (biceps + triceps + suprailiac + subscapular; Model 4) showed further improvement in the prediction of FM% as compared with SF2 (88% vs 86% of variance). CONCLUSIONS: The sum of 4 skinfolds is the most accurate in predicting FM% in paediatric IBD. The sum of 2 skinfolds is less accurate but more feasible and less prone to error. The newly developed population-specific formulae could be a valid tool for estimation of body composition in IBD population and an alternative to DEXA measurement.

Validation of an Accurate and Noninvasive Tool to Exclude Female Precocious Puberty: Pelvic Ultrasound With Uterine Artery Pulsatility Index.

OBJECTIVE. The purpose of this study is to validate the accuracy of pelvic ultrasound (US) with the evaluation of uterine artery pulsatility index (PI) to exclude female precocious puberty. MATERIALS AND METHODS. Tanner breast development score, luteinizing hormone (LH) peak after gonadotropin-releasing hormone (GnRH) stimulation, and uterine and ovarian volumes and diameters were assessed with pelvic US in 495 girls at a single institution. The study population was divided as follows: prepubertal (n = 207), pubertal with physiologic activation of the hypothalamic-pituitary-ovarian axis (n = 176), and central precocious puberty (CPP; n = 112). PI was measured with spectral Doppler US at the ascending branches of the right uterine artery (50-Hz filter; time gain compensation, 73; pulse repetition frequency, 6.6). ROC analyses and t tests were performed. RESULTS. The mean (± SD) PI values in the prepubertal, pubertal, and CPP groups were 6.3 ± 1.4, 3.4 ± 1.1, and 4.1 ± 1.5, respectively (p < 0.001). The best PI cutoff value to distinguish pubertal from prepubertal girls was 4.6 (sensitivity, 83%; specificity, 94%; positive predictive value, 95%; negative predictive value, 80%; accuracy, 87%). ROC AUC values for LH peak (cutoff value, 5 mU/mL) and for spectral Doppler US PI plus longitudinal uterine diameter (i.e., the combination of a PI of 4.6 with a longitudinal uterine diameter of 35 mm) were 0.9272 and 0.9439, respectively (p = 0.7925). The negative predictive values for LH peak and for PI plus longitudinal uterine diameter were 89% and 88%, respectively. CONCLUSION. A PI greater than 4.6 at spectral Doppler US combined with a longitudinal uterine diameter less than 35 mm allows noninvasive exclusion of female precocious puberty with comparable accuracy and lower costs compared to examination of LH peak after GnRH stimulation. Therefore, PI plus longitudinal uterine diameter might be used as a noninvasive first-line test to exclude precocious puberty and thereby avoid further investigations.

Mild TSH resistance: Clinical and hormonal features in childhood and adulthood.

OBJECTIVE: Mutations in TSH receptor (TSHR) are associated with TSH resistance, a genetic defect characterized by a heterogeneous phenotype ranging from severe hypothyroidism to subclinical hypothyroidism (SCH). We assessed the clinical and hormonal pattern of TSHR variants in a series of pediatric patients, and the long-term outcome of growth, biochemical measurements of metabolism, and neuropsychological functions in TSHR mutations carriers. DESIGN: Observational, retrospective study. PATIENTS: Thirty four children (age 7 days to 11 years) and 18 adult carriers of TSHR variants. MEASUREMENTS: The TSHR gene was sequenced by PCR-amplified direct sequencing in 111 pediatric patients with slight to moderate elevation of TSH and normal FT4 levels. The study focused on the: auxological and biochemical parameters, thyroid ultrasound, bone age, bone mineral density (BMD), and intellectual outcome (IQ) were collected during the long follow-up (1-15 years). RESULTS: Seventeen different TSHR variants (eight novel) were identified in 34 of the 111 pediatric patients, with a high prevalence of familial cases (27/34). Neonatal screening for congenital hypothyroidism was positive in half of the TSHR carriers. Growth, IQ, BMD, and biochemical parameters were normal in all subjects. Twenty patients received L-T4 replacement therapy, in all cases before genetic analysis. After re-evaluation, six patients resumed L-T4 therapy: they were compound heterozygous, or single heterozygous and with associated conditions at risk of thyroid impairment (SGA). No adults presented clinical features consistent with impaired thyroid function. CONCLUSIONS: Children carriers of TSHR variants, regardless of L-T4 treatment, show regular growth and neuropsychological development, with no evident biochemical and US alterations.

A biochemical approach for assessing cutoffs at the age thresholds of 14 and 18 years: a pilot study on the applicability of bone specific alkaline phosphatase on an Italian sample.

BACKGROUND: The majority of age estimation methods analyze morphological changes of specific skeletal (or dental) structures reflecting global bone development (biological parameter) in order to estimate a chronological value. This morphological and structural development is the consequence of a very active tissue metabolism and intensive modeling process which involve both bone formation and bone resorption. Several biochemical markers of bone formation and bone resorption are available, and specific biochemical tests can be performed on blood or urine samples, but such markers of bone turnover have never been employed for age estimation in living individuals for forensic purposes. The aim of this study was to ascertain the applicability of serum bone alkaline phosphatase (BALP) concentration in the age estimation for forensic purposes. We focused on the legal age thresholds of 14 and 18 years (LAT) because, in Italy, the former is considered the minimum age for criminal responsibility and the latter defines adult age and the possibility of applying general criminal laws. MATERIALS AND METHODS: This study analyzed, from a forensic point of view, BALP and Tanner stages of 202 healthy white individuals (116 females and 86 males) between the ages of 10 and 30 years. We derived a linear logistic model to estimate the probability that an individual was older or younger than LAT using two variables: BALP concentration and Tanner stages. The predictive accuracy of the test was assessed by the determination of the receiver-operating characteristic curve (ROC curve). The test was performed to identify a threshold (cutoff) that could be used to assign an individual to the population of those younger or older than LAT. RESULTS: ROC curve showed that the use of both serum BALP concentration and Tanner stages has a very good level of reliability in age assessment (the area under the ROC curve, AUC, ranged from 0.918 to 0.962). Best results were obtained in the assessment of male over 18 years of age (sensibility and specificity respectively of 0.90 and 0.93 with an accuracy of 0.92). Worst results were obtained in the assessment of female over 18 years of age (sensibility and specificity respectively of 0.87 and 0.82 with an accuracy of 0.84). We also calculated the probability of the correctness in the age estimation. CONCLUSION: The results showed that the use of serum BALP concentration in the age assessment could be a promising and integrative method to established ones, but more research has to be done to validate the value of the proposed method in the forensic practice.

Areal bone mineral density in pediatric patients with chronic hepatitis B or chronic hepatitis C.

Decreased bone mineral density (BMD) is a known complication of chronic liver disease in adults. Data on bone mass, an important factor for the development of osteoporosis in adult life, in young patients with chronic hepatitis B (HBV) and C virus (HCV) infections are scarce. We measured BMD at the lumbar spine and whole skeleton by dual-energy X-ray absorptiometry in 11 HBV- and 21 HCV-vertically infected untreated youths (3.9-21.1 years). BMD measurements were compared to those of 202 healthy subjects (3.0-21.9 years). The median BMD Z-score of the lumbar spine of HBV-infected patients was -0.3, ranging from -1.6 to 0.6, while the median whole skeleton BMD Z-score was 0.1 (-0.8 to 0.6). HBV-infected patients showed a median Z-score of the lumbar spine of 0.6 (-1.6 to 1.9), and a median whole skeleton BMD Z-score of 0.6, ranging from -1.5 to 1.4. Multivariate analyses have been performed to correct for differences in sex, age, and anthropometric measurements. Lumbar spine BMD values of HBV and HCV-infected patients were not significantly different from those of controls. Similarly, no differences were found between groups in total body BMD measurements. Our data suggest that, unlikely adult patients, untreated young patients with chronic HBV and HCV infection may not have impaired bone mass measurements.

Hypoparathyroidism: an update on new therapeutic approaches.

BACKGROUND: Hypoparathyroidism is a rare endocrine disease characterized by insufficient parathyroid hormone (PTH) secretion by the parathyroid glands, leading to hypocalcemia. In contrast to most hormone deficiencies for which hormone replacement is currently the mainstay of therapy, hypoparathyroidism has conventionally been treated with calcium supplements and active analogs of vitamin D. Although the advent of a replacement therapy with 1-34 and 1-84 PTH represented a major step in the therapeutic history of hypoparathyroidism, several new molecules and different management strategies have recently been developed. PURPOSE: This review investigates the therapeutic approaches currently under investigation for the treatment of hypoparathyroidism. Clinical trials results have been considered and discussed.

Diagnosis, treatment, and management of rickets: a position statement from the Bone and Mineral Metabolism Group of the Italian Society of Pediatric Endocrinology and Diabetology.

Rickets results from impaired mineralization of growing bone due to alterations in calcium and phosphate homeostasis. Clinical signs of rickets are related to the age of the patient, the duration of the disease, and the underlying disorder. The most common signs of rickets are swelling of the wrists, knees or ankles, bowing of the legs (knock-knees, outward bowing, or both) and inability to walk. However, clinical features alone cannot differentiate between the various forms of rickets. Rickets includes a heterogeneous group of acquired and inherited diseases. Nutritional rickets is due to a deficiency of vitamin D, dietary calcium or phosphate. Mutations in genes responsible for vitamin D metabolism or function, the production or breakdown of fibroblast growth factor 23, renal phosphate regulation, or bone mineralization can lead to the hereditary form of rickets. This position paper reviews the relevant literature and presents the expertise of the Bone and Mineral Metabolism Group of the Italian Society of Pediatric Endocrinology and Diabetology (SIEDP). The aim of this document is to provide practical guidance to specialists and healthcare professionals on the main criteria for diagnosis, treatment, and management of patients with rickets. The various forms of rickets are discussed, and detailed references for the discussion of each form are provided. Algorithms to guide the diagnostic approach and recommendations to manage patients with rare forms of hereditary rickets are proposed.

Antiretroviral therapy and pregnancy: effect on cortical bone status of human immunodeficiency virus-infected Caucasian women as assessed by quantitative ultrasonography.

Treatment with antiretroviral agents (ARVs) during pregnancy is important to prevent mother-to-child transmission of the human immunodeficiency virus (HIV), but their use has been associated with low bone mineral density in adult patients. Currently, there are no data regarding the bone status of HIV-infected women who received ARV during pregnancy. The aim of this study was to evaluate cortical bone status at delivery in a group of HIV-infected women who received ARV during pregnancy and to monitor the changes occurring during the first year postpartum. We studied 33 HIV-infected and 116 HIV-uninfected healthy Caucasian women within 4 days from delivery. Follow-up measurements were performed at 4 and 12 months postpartum in 17 HIV-infected and 55 healthy women. Cortical bone status was evaluated by quantitative ultrasonography at the mid-tibia, and bone measurements were expressed as the speed of sound (SOS). HIV-infected women after delivery had a median SOS of 3,985 (3,567-4,242) m/s, while the median SOS of healthy women was 4,025 (3,643-4,250) m/s. The difference was not significant (t = 0.39, P = 0.69). No significant differences were observed between ARV-exposed and control subjects at 4 and 12 months. Our data suggest that ARV during pregnancy and the first year after delivery does not affect negatively cortical bone status.

Cholecalciferol supplementation in HIV-infected youth with vitamin D insufficiency: effects on vitamin D status and T-cell phenotype: a randomized controlled trial.

OBJECTIVES: In addition to its known effects on bone metabolism, vitamin D may regulate immune function. DESIGN: We performed a randomized controlled trial (RCT) to test whether cholecalciferol supplementation can improve vitamin D status and affect the T-cell phenotype in HIV-infected youth with vitamin D insufficiency. METHODS: Fifty-two HIV-infected patients aged 8 to 26 years and with serum 25(OH) D <30 ng/mL were randomized to receive orally vitamin D3 100,000 IU or placebo every 3 months for 4 doses. Serum 25(OH)D, 1,25(OH)2D, PTH, and CD4+ T cells were assessed 3 months before baseline and at 0, 3, 6, 9, and 12 months, while Th1-, Th2-, Th17-, and Treg-subsets and T-lymphocyte vitamin D receptor were assessed at 0, 3, and 12 months. RESULTS: Forty-eight subjects (25 receiving vitamin D and 23 receiving placebo) completed the RCT. Cholecalciferol supplementation produced an early (3 months) decrease in PTH, a concomitant increase in 25(OH)D, and a later (6 months) increase in 1,25(OH)2D levels, all persisting at 12 months. The frequency of vitamin D insufficiency at 12 months was 20% versus 60% in the intervention versus placebo group (P = .007). Cholecalciferol supplementation had no effect on CD4+ T-cell counts but was associated with a decreased Th17:Treg ratio at 3 months. CONCLUSIONS: In our cohort of HIV-infected youth, a 12-month cholecalciferol supplementation increased 25(OH)D and 1-25(OH)2D and decreased PTH levels but had no effect on CD4+ T-cells. However, it was associated with changes in CD4+ T-cell phenotype, warranting further investigation.

Long-term body composition and metabolic changes in HIV-infected children switched from stavudine to tenofovir and from protease inhibitors to efavirenz.

UNLABELLED: This is an 8-year cohort study of 24 HIV-infected patients aged 5-17 years to assess body composition and metabolic changes after switching from lamivudine + stavudine (d4T) + protease inhibitors (PI) to lamivudine + tenofovir (TDF) + efavirenz (EFV). Body composition (dual-energy X-ray absorptiometry) and cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, triglycerides, glucose and insulin were measured annually. Linear mixed models and generalized linear mixed models were used to evaluate time changes of the outcome of interest. Body mass index increased linearly by 0.3 kg/m(2)/year (p < 0.001); waist circumference increased non-linearly from 68 to 74 cm (p = 0.004 for the linear term and p = 0.04 for the quadratic term). Percent body fat, percent trunk fat and percent bone mineral content increased linearly by 0.6%/year (p = 0.005), 1.2%/year (p < 0.001) and 0.02%/year (p = 0.04), respectively. Percent arm fat remained stable (p = 0.5), and percent leg fat decreased linearly by 1.2%/year (p < 0.001). The probability of low HDL was 0.2% at baseline and remained stable during the study. The probability of high triglycerides was 3% at baseline and increased linearly to become 11% at the 8th year of follow-up (p = ns). The probability of high glucose was 1% for the whole study duration. CONCLUSIONS: patients, after switching from d4T to TDF and from PI to EFV, show most of the changes in anthropometry and body composition associated with normal growth and no frankly pathological change in metabolic parameters.

Different Efficacy of Burosumab on Physical Performance and Serum Phosphate in Adult Patients with X-Linked Hyphophosphatemic Rickets during the First Six-Month of Treatment.

Burosumab is a monoclonal anti-FGF23 antibody used to treat patients with X-linked hypophosphatemic rickets (XLH). Its effect on serum phosphate and physical performance was compared in patients during a 6-month treatment with burosumab. Eight adult patients with XHL were treated with burosumab (1 mg/kg s.c. every 28 days). In the first 6 months of treatment, calcium-phosphate metabolism variables were measured, and muscle performance (tested with chair and walking test) and quality of life (tested with fatigue, BPI-pain and BPI-life questionnaires) were estimated. A significant increase in serum phosphate was observed during the treatment. From the 16th week, serum phosphate became significantly lower than its value in the 4th week. No patients had serum phosphate below the normal range at the 10th week, but seven patients were hypophosphatemic in the 20th and 24th week. All patients improved the execution time of the chair test and walking test, which reached a plateau after the 12th week. BPI-pain and BPI-life scores significantly decreased from baseline to the 24th week. In conclusion, a six-month burosumab treatment may significantly improve the general condition and physical performance of adult patients with XLH; this improvement was more stable and more indicative of treatment efficacy than that of serum phosphate.

Mutations in LRP5 cause primary osteoporosis without features of OI by reducing Wnt signaling activity.

BACKGROUND: Primary osteoporosis is a rare childhood-onset skeletal condition whose pathogenesis has been largely unknown. We have previously shown that primary osteoporosis can be caused by heterozygous missense mutations in the Low-density lipoprotein receptor-related protein 5 (LRP5) gene, and the role of LRP5 is further investigated here. METHODS: LRP5 was analyzed in 18 otherwise healthy children and adolescents who had evidence of osteoporosis (manifested as reduced bone mineral density i.e. BMD, recurrent peripheral fractures and/or vertebral compression fractures) but who lacked the clinical features of osteogenesis imperfecta (OI) or other known syndromes linked to low BMD. Also 51 controls were analyzed. Methods used in the genetic analyses included direct sequencing and multiplex ligation-dependent probe amplification (MLPA). In vitro studies were performed using luciferase assay and quantitative real-time polymerase chain reaction (qPCR) to examine the effect of two novel and three previously identified mutations on the activity of canonical Wnt signaling and on expression of tryptophan hydroxylase 1 (Tph1) and 5-hydroxytryptamine (5-Htr1b). RESULTS: Two novel LRP5 mutations (c.3446 T > A; p.L1149Q and c.3553 G > A; p.G1185R) were identified in two patients and their affected family members. In vitro analyses showed that one of these novel mutations together with two previously reported mutations (p.C913fs, p.R1036Q) significantly reduced the activity of the canonical Wnt signaling pathway. Such reductions may lead to decreased bone formation, and could explain the bone phenotype. Gut-derived Lrp5 has been shown to regulate serotonin synthesis by controlling the production of serotonin rate-limiting enzyme, Tph1. LRP5 mutations did not affect Tph1 expression, and only one mutant (p.L1149Q) reduced expression of serotonin receptor 5-Htr1b (p < 0.002). CONCLUSIONS: Our results provide additional information on the role of LRP5 mutations and their effects on the development of juvenile-onset primary osteoporosis, and hence the pathogenesis of the disorder. The mutations causing primary osteoporosis reduce the signaling activity of the canonical Wnt signaling pathway and may therefore result in decreased bone formation. The specific mechanism affecting signaling activity remains to be resolved in future studies.

Longitudinal changes of bone ultrasound measurements in healthy infants during the first year of life: influence of gender and type of feeding.

There is evidence suggesting that early events in life may predispose the adult to osteoporosis. We assessed bone status by quantitative ultrasonography in healthy neonates, and we report the changes occurring during the first year of life, according to the type of early feeding. We measured the speed of sound (SOS) of the left tibia in 116 full-term infants (0-9 days of age) and in their mothers (21-42 years of age). SOS values did not correlate with gestational age of the study subjects (r = 0.08) or anthropometric measurements. The SOS measurements of the mothers did not correlate with those of their children (r = 0.01). Fifty-seven infants had SOS measurements performed at 4 and 12 months. Twenty-five infants were exclusively breast-fed, 12 received formula milk from birth, and 20 received human and formula milk. SOS measurements at 4 months were comparable with those at baseline, whereas at 12 months they were significantly higher. No effect of type of feeding was observed, indicating that SOS changes may be independent of the type of early diet.

Optical properties of dibenzo[d,d']thieno[3,2-b;4,5-b']dithiophene monocrystals: the effect of intermolecular interactions.

The polarized UV-visible absorption spectra of dibenzo[d,d']thieno[3,2-b;4,5-b']dithiophene single crystals are reported and interpreted to definitively attribute the observed bands and their polarizations. The results provide information on the intermolecular interactions and on the aggregation in the condensed phase, which can be of either herringbone- or H-type, depending on the electronic transition taken into considerations, with consequences on the order and polarization of the absorption bands. A relatively easy method is also discussed to obtain information on the structural/morphological properties of different types of samples, including thin films, which have been recently proposed for high-performance organic film-effect transistors for their high ionization potential and photostability.

Anisotropic optical functions of α-1,4,4-tetraphenyl-1,3-butadiene.

One of the known monoclinic polymorphs of 1,1,4,4-tetraphenyl-1,3-butadiene was grown by the floating-drop technique. This material is of interest for blue emitting devices and for fundamental studies on intermolecular interactions, excited states and vibronic coupling in the fields of chemical physics and materials science. Polarized UV-visible spectra are reported. The origin of the optical bands is resolved. The results give information on the intermolecular interactions and are compared with theoretical predictions and modeling. The full material dielectric tensor is provided, as deduced from generalized spectroscopic ellipsometry. Details on the use of this technique on strongly anisotropic and absorbing molecular materials are given. Some typical features of the optical spectra are also demonstrated to be very sensitive to the presence of misaligned domains, which, in our samples, are found to be rotated around the normal to the surface and whose amount is determined. The method allows discriminating among monocrystals, in-plane polycrystalline samples, layered samples formed by misaligned successive layers, or samples with both types of disorder. Two independent parameters giving the fraction of misaligned domains or layers are suggested for the characterization and optimization of the growth and deposition of molecular organic materials.

X-Linked Hypophosphatemic Rickets: Multisystemic Disorder in Children Requiring Multidisciplinary Management.

X-linked hypophosphatemic rickets (XLH) is the commonest inherited form of rickets. It is caused by an impaired regulation of fibroblast growth factor 23 (FGF23) due to a PHEX gene mutation, which leads to reduced tubular reabsorption of phosphate and renal 1α-hydroxylase activity and increased renal 24-hydroxylase activity. Hypophosphatemia associated with renal phosphate wasting, normal serum levels of calcium, parathyroid hormone, and 25-hydroxyvitamin D represents the main biochemical sign in affected patients. Patients with XLH show rickets and osteomalacia, severe deformities of the lower limbs, bone and muscular pain, stunted growth, and reduced quality of life. However, XLH is a multisystemic disorder requiring multidisciplinary approaches in specialized subdisciplines. Severe complications may occur in patients with XLH including craniosynostosis, hearing loss, progressive bone deformities, dental and periodontal recurrent lesions, and psychosocial distress. Moreover, long-term conventional treatment with active vitamin D metabolites and oral inorganic phosphate salts may cause endocrinological complications such as secondary or tertiary hyperparathyroidism, and adverse events in kidney as hypercalciuria, nephrocalcinosis, and nephrolithiasis. However, conventional treatment does not improve phosphate metabolism and it shows poor and slow effects in improving rickets lesions and linear growth. Recently, some trials of treatment with recombinant human IgG1 monoclonal antibody that targets FGF23 (burosumab) showed significant improvement of serum phosphate concentration and renal tubular reabsorption of phosphate that were associated with a rapid healing of radiologic signs of rickets, reduced muscular and osteoarticular pain, and improved physical function, being more effective for the treatment of patients with XLH in comparison with conventional therapy. Therefore, a global management of patients with XLH is strongly recommended and patients should be seen regularly by a multidisciplinary team of experts.

Body Fat Distribution and Metabolic Changes in a Cohort of Adolescents Living With HIV Switched to an Antiretroviral Regimen Containing Dolutegravir.

Use of antiretrovirals is associated to body fat accumulation. We measured body composition in adolescents living with HIV switched to a dolutegravir-containing regimen. Trunk fat and trunk/body fat ratio markedly increased after 12 months. Total and low density lipoprotein cholesterol decreased after 3 months. Increase in trunk fat may put at risk of future cardiovascular problems, despite improvement in the lipid profile.

Bone mineral density surveillance for childhood, adolescent, and young adult cancer survivors: evidence-based recommendations from the International Late Effects of Childhood Cancer Guideline Harmonization Group.

Childhood, adolescent, and young adult cancer survivors are at increased risk of reduced bone mineral density. Clinical practice surveillance guidelines are important for timely diagnosis and treatment of these survivors, which could improve bone mineral density parameters and prevent fragility fractures. Discordances across current late effects guidelines necessitated international harmonisation of recommendations for bone mineral density surveillance. The International Late Effects of Childhood Cancer Guideline Harmonization Group therefore established a panel of 36 experts from ten countries, representing a range of relevant medical specialties. The evidence of risk factors for very low and low bone mineral density and fractures, surveillance modality, timing of bone mineral density surveillance, and treatment of very low and low bone mineral density were evaluated and critically appraised, and harmonised recommendations for childhood, adolescent, and young adult cancer survivors were formulated. We graded the recommendations based on the quality of evidence and balance between potential benefits and harms. Bone mineral density surveillance is recommended for survivors treated with cranial or craniospinal radiotherapy and is reasonable for survivors treated with total body irradiation. Due to insufficient evidence, no recommendation can be formulated for or against bone mineral density surveillance for survivors treated with corticosteroids. This surveillance decision should be made by the survivor and health-care provider together, after careful consideration of the potential harms and benefits and additional risk factors. We recommend to carry out bone mineral density surveillance using dual-energy x-ray absorptiometry at entry into long-term follow-up, and if normal (Z-score > -1), repeat when the survivor is aged 25 years. Between these measurements and thereafter, surveillance should be done as clinically indicated. These recommendations facilitate evidence-based care for childhood, adolescent, and young adult cancer survivors internationally.

[Comparative study of the short-term effect of mineral water on calcium metabolism]. / Studio comparativo dell'effetto a breve termine di due acque minerali sul metabolismo del calcio.

Mineral water may be a useful means to achieve optimal dietary calcium intake, but the effect of different mineral waters on calcium metabolism is unknown. We therefore evaluated calcium excretion in 24-hour urine in 10 healthy individuals (5 women and 5 men) after two weeks of drinking at least 1500 mL/day of mineral water with a low electrolyte content or 1500 mL/day of mineral water rich in calcium and bicarbonate but with a different sodium content. The low-sodium water Sangemini was one of these two mineral waters. Calcium excretion did not significantly increase after intake of the Sangemini mineral water in comparison with the baseline period of low-electrolyte mineral water intake. Conversely, the calcium excretion increased significantly after intake of the second mineral water. The plasma concentration of C-terminal telopeptide of type I collagen and the urinary phosphate excretion decreased after intake of the second mineral water in comparison with the baseline period, whereas they did not decrease after intake of Sangemini water. Therefore, phosphate excretion was higher after drinking Sangemini water than the other studied mineral water. Drinking Sangemini water may have a slight effect on calcium excretion and may not inhibit bone turnover in the short term. The lesser effect of Sangemini water on calcium excretion could be useful in the treatment of osteoporosis.

Increased fracture rate in children and adolescents with Marfan syndrome.

Marfan syndrome (MFS) is an autosomal genetic disorder of connective tissue, due to alterated fibrillin-1. The aim of our study was to verify the rate of fractures in children with MFS in correlation to bone mineral density and compare the prevalence to the general population in the same latitude. We enrolled 80 patients (37 girls and 43 boys) with the diagnosis of Marfan syndrome, median age 10 y (3 to 17 years). Fracture occurrence was inferred from medical records of patients with MFS. Bone mineral density (BMD) was measured at lumbar spine, femoral neck and total femur by dual-energy x-ray absorptiometry. BMD values were expressed as z-scores, and adjusted for height using height-for-age z-scores. Bone turnover markers and vitamin D were measured. We assessed incidence of fracture in general pediatric population of our geographic area (45°N latitude). A total of 24 fractures were recorded in 21 patients (15 boys and 6 girls), involving both short and long bones, due to mild or moderate trauma. An incidence estimate has been calculated for each year, and an average incidence of 29.2/1000 MFS patients was obtained, markedly higher (P=0.034) than the incidence of fracture calculated in the same geographical area in pediatric patients (15.8/1000). We did not detect differences in anthropometric measurements, BMD values and biochemical indices between patients who fractured and patients who did not. Similarly, no differences were found between patients on losartan therapy and patients not in treatment for the same variables. In conclusion, the incidence of fractures was higher in patients with MFS compared to general population of the same age and latitude. The management of MFS must account bone status health and start strategies of fracture prevention.