F. Vierucci

Vitamin D in childhood and adolescence: an expert position statement

AbstractVitamin D is a key hormone in the regulation of calcium and phosphorus metabolism and plays a pivotal role in bone health, particularly during pediatric age when nutritional rickets and impaired bone mass acquisition may occur. Great interest has been placed in recent years on vitamin D’s extraskeletal actions. However, while recent data suggest a possible role of vitamin D in the pathogenesis of several pathological conditions, including infectious and autoimmune diseases, the actual impact of vitamin D status on the global health of children and adolescents, other than bone, remains a subject of debate. In the meantime, pediatricians still need to evaluate the determinants of vitamin D status and consider vitamin D supplementation in children and adolescents at risk of deficiency. This review is the result of an expert meeting that was held during the congress “Update on vitamin D and bone disease in childhood” convened in Pisa, Italy, in May 2013. Conclusion: The collaboration of the international group of experts produced this “state of the art” review on vitamin D in childhood and adolescence. After dealing with vitamin D status and its determinants, the review outlines the current debate on vitamin D’s health benefits, concluding with a practical approach to vitamin D supplementation during childhood and adolescence.What is Known:• Vitamin D deficiency is a worldwide health problem.• Vitamin D deficiency affects not only musculoskeletal health but also a potentially wide range of acute and chronic diseases.What is New:• We reviewed the literature focusing on randomized controlled trials of vitamin D supplementation during childhood and adolescence.• This review will help pediatricians to appreciate the clinical relevance of an adequate vitamin D status and it will provide a practical approach to vitamin D supplementation.

Analysis of quantitative ultrasound graphic trace and derived variables assessed at proximal phalanges of the hand in healthy subjects and in patients with cerebral palsy or juvenile idiopathic arthritis. A pilot study.

Amplitude-dependent speed of sound (AD-SoS) and bone transmission time (BTT) are the quantitative ultrasound (QUS) variables usually assessed at proximal phalanges of the hand to estimate bone mineral status. The aim of the study was to provide a reference database for some additional QUS variables reflecting morphology of the ultrasound graphic trace according to gender, age, height, weight, and body mass index (BMI), and to assess their clinical usefulness. Fifty-two patients (age 3.1-20.9 years) affected by cerebral palsy with spastic tetraplegia (CPST, n=38) or polyarticular active juvenile idiopathic arthritis (JIA, n=14) were examined. In addition to AD-SoS and BTT, two QUS variables derived from the morphological analysis of ultrasound graphic trace, such as energy, extrapolated from the area under the ultrasound signal received, and weighted-slope (W-slope), derived from the angular coefficient of the regression line fitting the top point of the peaks of the ultrasound signal, were measured by phalangeal QUS (DBM Sonic, IGEA). The values of all the QUS variables measured in the patients were compared with our own sex- and age-reference values (n=1083, 587 males and 496 females, aged 3-21 years). The mean values of AD-SoS, BTT, energy, and W-slope were reduced (P<0.0001) in patients as a whole compared with normative data (-2.4+/-1.2, -2.7+/-1.5, -2.5+/-1.1, -2.5+/-1.1 Z-score, respectively). Fractured patients showed lower (P<0.001-P<0.0001) values of the QUS variables than fracture-free patients (AD-SoS, -3.3+/-1.2 and -1.8+/-0.9; BTT, -3.9+/-1.7 and -1.8+/-1.1; energy, -3.2+/-1.2 and -2.2+/-0.7; W-slope, -3.4+/-1.4 and -2.2+/-0.9 Z-score, respectively). There was no difference (P=NS) between patients with CPST and those with JIA. Age and height were positively correlated with all the QUS variables (r=0.55-0.79, P<0.01-P<0.0001). QUS variables were positively correlated among them (r=0.74-0.94, P<0.0001). Age and number of fractures were independent predictors of the QUS variables (coefficients: AD-SoS, 11.466 and -17.642; BTT, 0.049 and -0.045; energy, 1.072 and -1.303; W-slope, 0.046 and -0.067; respectively). In conclusion, measurement of QUS variables derived from the morphological analysis of the ultrasound signal could give additional information in estimating bone mineral status in children and adolescents, probably reflecting some aspect related to bone structure.

Erythema multiforme as first sign of incomplete Kawasaki disease

Incomplete Kawasaki disease represents a diagnostic challenge for pediatricians. In the absence of classical presentation, the laboratoristic evaluation of systemic inflammation can help in placing the correct diagnosis to promptly start adequate therapy. Erythema multiforme is an acute, self-limiting condition considered to be a hypersensitivity reaction commonly associated with various infections or medications. This aspecific skin condition has been rarely described as a sign of Kawasaki disease. We report on the case of a 4 years old boy presenting high-grade fever associated with erythema multiforme and evidence of systemic inflammation who showed a good response to prompt treatment with intravenous immunoglobulins.

Usefulness of phalangeal quantitative ultrasound in identifying reduced bone mineral status and increased fracture risk in adolescents with Turner syndrome

OBJECTIVE. Bone health is a major concern in patients with Turner syndrome (TS). There are few studies assessing bone mineral status in TS adolescents and none have reported a clear relationship with the risk of fracture. We assessed bone mineral status at three different skeletal sites by two different densitometric techniques in a group of TS adolescents. DESIGN. In 24 TS adolescents (17.1 ± 3.1 years) we evaluated lumbar and femoral volumetric bone mineral density (vBMD) with dual energy X-ray absorptiometry (DXA), amplitude-dependent speed of sound (AD-SoS) and bone transmission time (BTT) with phalangeal quantitative ultrasound (QUS). RESULTS. Mean lumbar vBMD Z-score was normal, while mean femoral vBMD, ADSoS and BTT Z-score were reduced. 8/24 (33.3%) and 13/24 (54.2%) girls had AD-SoS and BTT ≤-2 Z-score, respectively, while lumbar vBMD and femoral vBMD were ≤-2 Z-score only in 2/24 (8.4%) and 1/24 (4.2%) patients. Overall, we documented 15 fractures (three pathological) in 8 girls. Patients who reported at least one fracture had lower AD-SoS and BTT Z-score values than fracture-free girls. The presence of a value of BTT ≤-2.0 Z-score was associated with a significant OR of positive history of fracture of 11.67 (χ2 = 5.906, p =0.015, C.I. 95% 1.14–119.54). Lumbar and femoral vBMD were not related to fracture risk. CONCLUSIONS. TS adolescents may have impaired bone mineral status in skeletal sites with predominant cortical bone. Phalangeal QUS represents a useful method to identify subjects with increased fracture risk.

Vitamin D in the perinatal period: an update

Vitamin D is a pleiotropic hormone modulating calcium and phosphorous metabolism. Numerous extraskeletal functions of vitamin D have been shown in recent years and the role of an adequate vitamin D status during pregnancy in terms of benefits for mother and child has been investigated. Presumed effects on pregnancy course include reduction in risk of pre-eclampsia, caesarian and preterm delivery and gestational diabetes mellitus. Short term outcomes in the offspring such as skeletal development, birthweight, and incidence of infections have also been postulated. Finally, long term effects of maternal vitamin D status during pregnancy on infant and child health would include bone health, neurodevelopment and incidence of asthma, infections and autoimmune diseases such as type 1 diabetes mellitus. As vitamin D deficiency is widespread among pregnant women all over the world, supplementation during pregnancy is a hot topic in literature, also in the light of these recent acquisitions. This review will summarize the most recent advances in this field.

Osteoporosis in childhood

Purpose of review The aim of this review is to highlight recent findings in prevention, diagnosis, and treatment of pediatric osteoporosis. Recent findings Several genes are involved in bone mass acquisition, and various monogenic bone disorders characterized by reduced bone mineral density and increased bone fragility have been recently described. Moreover, many chronic diseases and/or their treatment have been associated with impaired bone mass acquisition. Pediatric osteoporosis should be adequately suspected and properly diagnosed in children at risk of fractures. Particularly, detection of vertebral fracture allows the diagnosis regardless of densitometric evaluation. Dual X-ray absorptiometry remains the most widely used densitometric technique in childhood, but interpretation of results should be made with caution because of different confounding factors. Bisphosphonates represent one of the main medical treatments of pediatric osteoporosis, and many different protocols have been proposed. Bisphosphonates administration should be characterized by a first phase, followed by a period of maintenance. Optimal route of administration, duration of therapy, and long-term safety of bisphosphonates treatment require further investigation. Summary Careful monitoring of children at risk of fractures is essential to pose early diagnosis of osteoporosis. In children with persistent risk factors and reduced probability of spontaneous recovery, medical treatment with bisphosphonates should be considered.

Vitamin D Status and Predictors of Hypovitaminosis D in Internationally Adopted Children

Objectives To evaluate vitamin D status in internationally adopted children at first medical evaluation in Italy and to identify possible risk factors for hypovitaminosis D in this population. Methods 25-hydroxyvitamin D [25(OH)D] levels were analyzed in internationally adopted children consecutively recruited at one Italian Center between 2010 and 2014 as part of the first screening protocol. Demographic, clinical and laboratory data were prospectively collected. Serum 25(OH)D levels <10 ng/mL, <20 ng/mL, and <30 ng/mL were used to define severe vitamin D deficiency, vitamin D deficiency and hypovitaminosis D, respectively. Results 962 internationally adopted children (median age: 5.47 years; IQR:3.14–7.93) were included in the study. Median 25(OH)D level was 22.0 ng/mL (IQR:15.0–30.0 ng/mL); 710/962 (73.8%) children showed hypovitaminosis D (<30 ng/mL), 388/962 (40.3%) had vitamin D deficiency (<20 ng/dL), and 92/962 (9.6%) had severe vitamin D deficiency (<10ng/mL). No case of clinical rickets was observed. Hypovitaminosis D was particularly frequent (>90%) in children adopted from Ethiopia, Peru, India, Bulgaria and Lithuania. At multivariate analysis an increased risk of hypovitaminosis D was found to be associated with: age ≥ 6 years, time spent in Italy ≥ 3 months, blood sample taken in winter, spring or fall, compared to summer. Gender, ethnicity/continent of origin, tubercular infection, intestinal parassitosis and BMI-z-score < -2 were not associated with vitamin D status. Conclusion Hypovitaminosis D is common in internationally adopted children, from all ethnic group. The evaluation of serum 25(OH)D level could be useful early after the adoption to promptly start vitamin D supplementation/treatment if needed.

Vitamin D in pediatric age: consensus of the Italian Pediatric Society and the Italian Society of Preventive and Social Pediatrics, jointly with the Italian Federation of Pediatricians

Vitamin D plays a pivotal role in the regulation of calcium-phosphorus metabolism, particularly during pediatric age when nutritional rickets and impaired bone mass acquisition may occur.Besides its historical skeletal functions, in the last years it has been demonstrated that vitamin D directly or indirectly regulates up to 1250 genes, playing so-called extraskeletal actions. Indeed, recent data suggest a possible role of vitamin D in the pathogenesis of several pathological conditions, including infectious, allergic and autoimmune diseases. Thus, vitamin D deficiency may affect not only musculoskeletal health but also a potentially wide range of acute and chronic conditions. At present, the prevalence of vitamin D deficiency is high in Italian children and adolescents, and national recommendations on vitamin D supplementation during pediatric age are lacking. An expert panel of the Italian Society of Preventive and Social Pediatrics reviewed available literature focusing on randomized controlled trials of vitamin D supplementation to provide a practical approach to vitamin D supplementation for infants, children and adolescents.

The Spectrum of Vitamin D Deficiency: Description of a Family

Background Vitamin D deficiency represents a global health problem, affecting children and adolescents worldwide. Objects To confirm that vitamin D deficiency can present as a spectrum of clinical pictures. Methods We diagnosed nutritional rickets in a 10-month-old infant of Senegal origin with several risk factors for vitamin D deficiency. As many of these factors affected also his cohabitant relatives, we evaluate infants family members (mother and 4 brothers) looking for other vitamin D deficiency-related comorbidities. Results 3 brothers had asymptomatic vitamin D deficiency and 2 of them (9.8 and 13.4 years-old) showed secondary hyperparathyroidism. The fourth brother (11.3 years-old) had nutritional rickets. Their mother was affected by osteomalacia. None of them received vitamin D supplementation. Conclusion Vitamin D deficiency may present as a spectrum of clinical pictures, representing a continuum ranging from asymptomatic/subtle conditions to overt rickets/osteomalacia. Immigrant families are at high risk for vitamin D deficiency at every age. If a case of symptomatic vitamin D deficiency is recognized, then the evaluation of the all family members is recommended, as they can have the same and/or other risk factors for vitamin D deficiency.

Misurazione della massa ossea in pediatria

Circa il 90% della massa ossea viene accumulata entro le prime due decadi di vita soprattutto per l’effetto di fattori genetici (80%). I fattori ambientali, in particolare l’attivita fisica e l’apporto dietetico di calcio, sono importanti per il raggiungimento del potenziale genetico e per l’acquisizione di un adeguato picco di massa ossea che sembra rappresentare uno dei principali fattori per la prevenzione dell’osteoporosi nell’eta adulto-senile [1]. La misurazione della massa ossea durante l’eta evolutiva ha quindi un ruolo fondamentale per identificare i soggetti che potrebbero essere esposti a un aumentato rischio di fratture da osteoporosi nell’eta adulta.