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 in childhood and adolescence: an expert position statement.

UNLABELLED: Vitamin 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.

Growth impairment in children with atrophic autoimmune thyroiditis and pituitary hyperplasia.

BACKGROUND: Atrophic autoimmune thyroiditis (AAT) is a rare phenotype of autoimmune thyroiditis (AT) in pediatric age. AAT occurs without thyroid enlargement leading to a delay in its diagnosis. Growth impairment is infrequent in autoimmune thyroiditis, if timely diagnosed. Prolonged severe hypothyroidism is a rare cause of pituitary hyperplasia (PH) in childhood. Loss of thyroxine negative feedback causes a TRH-dependent hyperplasia of pituitary thyrotroph cells resulting in adenohypophysis enlargement. A transdifferentiation of pituitary somatotroph cells into thyrotroph cells could explain growth failure in those patients. METHODS: Twelve patients were retrospectively evaluated at five Italian and Polish Centres of Pediatric Endocrinology for height growth impairment. In all Centres, patients underwent routine clinical, biochemical and radiological evaluations. RESULTS: At the time of first assessment, the 75% of patients presented height growth arrest, while the remaining ones showed growth impairment. The study of thyroid function documented a condition of hypothyroidism, due to AT, in the entire cohort, although all patients had no thyroid enlargement. Thyroid ultrasound showed frankly atrophic or normal gland without goiter. Cerebral MRI documented symmetrical enlargement of the adenohypophysis in all patients and a homogeneous enhancement of the gland after the administration of Gadolinium-DPTA. Replacement therapy with levothyroxine was started and patients underwent close follow-up every 3 months. During the 12 months of follow-up, an improvement in terms of height growth has been observed in 88% of patients who continued the follow-up. Laboratory findings showed normalization of thyroid function and the control brain MRI documented complete regression of PH to a volume within the normal range for age and sex. CONCLUSIONS: This is the largest pediatric cohort with severe autoimmune primary hypothyroidism without goiter, but with pituitary hyperplasia in which significant growth impairment was the most evident presenting sign. AAT phenotype might be correlated with this specific clinical presentation. In youths with growth impairment, hypothyroidism should always be excluded even in the absence of clear clinical signs of dysthyroidism.

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.

Pamidronate treatment stimulates the onset of recovery phase reducing fracture rate and skeletal deformities in patients with idiopathic juvenile osteoporosis: comparison with untreated patients.

Although spontaneous remission occurs in patients with idiopathic juvenile osteoporosis (IJO), permanent bone deformities may occur. The effects of long-term pamidronate treatment on clinical findings, bone mineral status, and fracture rate were evaluated. Nine patients (age 9.8 ± 1.1 years, 7 males) with IJO were randomized to intravenous pamidronate (0.8 ± 0.1 mg/kg per day for 3 days; cycles per year 2.0 ± 0.1; duration 7.3 ± 1.1 years; n = 5) or no treatment (n = 4). Fracture rate, phalangeal quantitative ultrasound, and lumbar bone mineral density (BMD) by dual energy X-ray absorptiometry at entry and during follow-up (range 6.3-9.4 years) were assessed. Bone pain improved in treated patients. Difficulty walking continued for 3-5 years in untreated patients, and vertebral collapses occurred in three of them. During follow-up, phalangeal amplitude-dependent speed of sound (AD-SoS), bone transmission time (BTT), and lumbar BMDarea and BMDvolume progressively increased in treated patients (P < 0.05-P < 0.0001). In untreated patients AD-SoS and BTT decreased during the first 2-4 years of follow-up (P < 0.05-P < 0.01); lumbar BMDarea increased after 6 years (P < 0.001) whereas BTT and lumbar BMDvolume increased after 7 years of follow-up (P < 0.05 and P < 0.001, respectively). At the end of follow-up, AD-SoS, BTT, lumbar BMDarea, and BMDvolume Z-scores were lower in untreated patients than in treated patients (-2.2 ± 0.3 and -0.5 ± 0.2; -1.9 ± 0.2 and -0.6 ± 0.2; -2.3 ± 0.3 and -0.7 ± 0.3; -2.4 ± 0.2 and -0.7 ± 0.3, P < 0.0001, respectively). Fracture rate was higher in untreated patients than in treated patients during the first 3 years of follow-up (P < 0.02). Our study showed that spontaneous recovery of bone mineral status is unsatisfactory in patients with IJO. Pamidronate treatment stimulated the onset of recovery phase reducing fracture rate and permanent disabilities without evidence of side-effects.

Vitamin D status and predictors of hypovitaminosis D in Italian children and adolescents: a cross-sectional study.

UNLABELLED: Hypovitaminosis D affects children and adolescents all around the world. Italian data on vitamin D status and risk factors for hypovitaminosis D during pediatric age are lacking. Six hundred fifty-two children and adolescents (range 2.0-21.0 years) living in the northwestern area of Tuscany were recruited at the Department of Pediatrics, University Hospital Pisa. None of them had received vitamin D supplementation in the previous 12 months. 25-hydroxyvitamin D (25-OH-D) and parathyroid hormone (PTH) levels were analyzed in all subjects. Severe vitamin D deficiency was defined as serum levels of 25-OH-D<25.0 nmol/L (10.0 ng/mL) and vitamin D deficiency a<50.0 nmol/L (20.0 ng/mL). Serum 25-OH-D levels of 50.0-74.9 nmol/L (20.0-29.9 ng/mL) indicated vitamin D insufficiency, whereas 25-OH-D levels ≥ 75.0 nmol/L (30.0 ng/mL) were considered sufficient. Hypovitaminosis D was defined as 25-OH-D levels<75.0 nmol/L (30.0 ng/mL). The median serum 25-OH-D level was 51.8 nmol/L, range 6.7-174.7 (20.7 ng/mL, range 2.7-70.0), with a prevalence of vitamin D deficiency, insufficiency, and sufficiency of 45.9, 33.6, and 20.5 %, respectively. The prevalence of severe vitamin D deficiency was 9.5 %. Adolescents had lower median 25-OH-D levels (49.8 nmol/L, range 8.1-174.7; 20.0 ng/mL, range 3.2-70.0) than children (55.6 nmol/L, range 6.8-154.6; 22.3 ng/mL, range 2.7-61.9, p=0.006). Non-white individuals (n=37) had median serum 25-OH-D levels in the range of deficiency (28.2 nmol/L, range 8.1-86.2; 11.3 ng/mL, range 3.2-34.5), with 36/37 having hypovitaminosis D. Logistic regression showed significant increased risk of hypovitaminosis D in the following: blood samples taken in winter (odds ratio (OR) 27.20), spring (OR 26.44), and fall (OR 8.27) compared to summer; overweight (OR 5.02) and obese (OR 5.36) subjects compared to individuals with normal BMI; low sun exposure (OR 8.64) compared to good exposure, and regular use of sunscreens (OR 7.06) compared to non-regular use. Gender and place of residence were not associated with vitamin D status. The 25-OH-D levels were inversely related to the PTH levels (r=-0.395, p<0.0001). Sixty-three out of the 652 (9.7 %) subjects showed secondary hyperparathyroidism. CONCLUSION: Italian children and adolescents who were not receiving vitamin D supplementation had high prevalence of hypovitaminosis D. Careful identification of factors affecting vitamin D status is advisable to promptly start vitamin D supplementation in children and adolescents.

Perinatal asphyxia and hypothermic treatment from the endocrine perspective.

Introduction: Perinatal asphyxia is one of the three most important causes of neonatal mortality and morbidity. Therapeutic hypothermia represents the standard treatment for infants with moderate-severe perinatal asphyxia, resulting in reduction in the mortality and major neurodevelopmental disability. So far, data in the literature focusing on the endocrine aspects of both asphyxia and hypothermia treatment at birth are scanty, and many aspects are still debated. Aim of this narrative review is to summarize the current knowledge regarding the short- and long-term effects of perinatal asphyxia and of hypothermia treatment on the endocrine system, thus providing suggestions for improving the management of asphyxiated children. Results: Involvement of the endocrine system (especially glucose and electrolyte disturbances, adrenal hemorrhage, non-thyroidal illness syndrome) can occur in a variable percentage of subjects with perinatal asphyxia, potentially affecting mortality as well as neurological outcome. Hypothermia may also affect endocrine homeostasis, leading to a decreased incidence of hypocalcemia and an increased risk of dilutional hyponatremia and hypercalcemia. Conclusions: Metabolic abnormalities in the context of perinatal asphyxia are important modifiable factors that may be associated with a worse outcome. Therefore, clinicians should be aware of the possible occurrence of endocrine complication, in order to establish appropriate screening protocols and allow timely treatment.

Exclusive Breastfeeding and Vitamin D Supplementation: A Positive Synergistic Effect on Prevention of Childhood Infections?

Human milk is the best food for infants. Breastfeeding has been associated with a reduced risk of viral and bacterial infections. Breast milk contains the perfect amount of nutrients needed to promote infant growth, except for vitamin D. Vitamin D is crucial for calcium metabolism and bone health, and it also has extra-skeletal actions, involving innate and adaptive immunity. As exclusive breastfeeding is a risk factor for vitamin D deficiency, infants should be supplemented with vitamin D at least during the first year. The promotion of breastfeeding and vitamin D supplementation represents an important objective of public health.

Gestational vitamin D3 supplementation and sun exposure significantly influence cord blood vitamin D status and 3-epi-25-hydroxyvitamin D3 levels in term newborns.

BACKGROUND AND AIMS: High prevalence of hypovitaminosis D is worldwide reported among pregnant women and newborns. We assessed cord blood 25-hydroxyvitamin D3 [25(OH)D3] and 3-epi-25-hydroxyvitamin D3 (C3-epimer) levels in relation to assumed maternal risk factors for hypovitaminosis D. METHODS: We enrolled 246 term newborns during summer. 175/246 mothers were supplemented with a daily variable dosage (200-1,000 IU) of vitamin D3 during pregnancy. Cord blood 25(OH)D3 and C3-epimer concentrations were analyzed by high performance liquid chromatography tandem mass spectrometry. RESULTS: Median cord blood 25(OH)D3 levels were 23.4 ng/mL (16.9-28.8). The prevalences of vitamin D sufficiency (≥ 30.0 ng/mL), insufficiency (20.0-29.9 ng/mL), and deficiency (< 20.0 ng/mL) were 19.9%, 45.9%, and 34.2%, respectively. Non-Caucasian ethnicity, housewife life, weight excess, negligible sun exposure and absent gestational vitamin D supplementation were associated with both reduced cord blood 25(OH)D3 and C3-epimer levels. C3-epimer/25(OH)D3 ratio was 15.1% (13.6%-18.4%) and it was not related to any of the assumed risk factors for hypovitaminosis D. CONCLUSIONS: Cord blood vitamin D deficiency was common, particularly in newborns from mother not receiving vitamin D supplementation and with poor sun exposure. C3-epimer levels were high in cord blood, causing possible misclassification of vitamin D status if they were not distinguished from 25(OH)D3 concentrations.

How COVID-19 Pandemic Changed Children and Adolescents Use of the Emergency Department: the Experience of a Secondary Care Pediatric Unit in Central Italy.

Italy was the first European country hit by SARS-CoV-2 infection, particularly northern regions. After the beginning of national lockdown (March 9th, 2020), we observed a significant decrease in pediatric emergency department consultations (daily pediatric visits; pre-lockdown, 16 (11-22); lockdown, 3 (1-3); phase 2, 3 (3-5), p < 0.0001). On the other hand, the percentage of children discharged right after pediatric visit significantly decreased from 80% in January to 50% in April. After March 9th, we registered a change in the diagnoses of emergency department visits, with an increase in the percentage of non-infectious acute conditions and a decrease in infectious diseases, with two cases of a noteworthy delayed access to hospital care. We performed a retrospective analysis of consultations requested to our pediatric unit for children and adolescents referred to the general Emergency Department of San Luca Hospital of Lucca (Tuscany, Central Italy) from January 1st to May 31st, 2020. We split data in two different time periods according to consultations performed before (January 1st-March 8th) and after the beginning of lockdown (March 9th-May 31st). Analyzing the number of children hospitalized from January to May 2020 in comparison with the same period in 2019, a decreased hospitalization became evident after March (March - 74.6%, April - 71.6%, May - 58.6%). Nasopharyngeal swabs done in 115 children showed only one case of COVID-19. Even if COVID-19 outbreak more seriously affected Northern Italy, utilization of pediatric emergency services significantly changed also in Central Italy with consequent reduced demand and increased appropriateness.

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 infant's 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.

Skin advanced glycation end-products evaluation in infants according to the type of feeding and mother's smoking habits.

OBJECTIVES: This study was conducted to assess whether formula-fed infants had increased skin advanced glycation end-products compared with breastfed ones. We also evaluated the effect of maternal smoke during pregnancy and lactation on infant skin advanced glycation end-products accumulation. METHODS: Advanced glycation end-product-linked skin autofluorescence was measured in 101 infants. RESULTS: In infants born from non-smoking mothers, advanced glycation end-products were higher in formula-fed subjects than in breastfed subjects (0.80 (0.65-0.90) vs 1.00 (0.85-1.05), p < 0.001). Advanced glycation end-products in breastfed infants from smoking mothers were higher than in those from non-smoking mothers (0.80 (0.65-0.90) vs 1.00 (0.90-1.17), p = 0.009). CONCLUSION: Formula-fed infants had increased amounts of advanced glycation end-products compared with the breastfed ones, confirming that breast milk represents the best food for infants. Breastfed infants from mothers smoking during pregnancy and lactation had increased skin advanced glycation end-products, suggesting that smoke-related advanced glycation end-products transfer throughout breast milk. Moreover, advanced glycation end-products may already increase during gestation, possibly affecting fetal development. Thus, we reinforced that smoking must be stopped during pregnancy and lactation.

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.

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, AD-SoS 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.

Prevalence of hypovitaminosis D and predictors of vitamin D status in Italian healthy adolescents.

BACKGROUND: Vitamin D plays an important role in health promotion during adolescence. Vitamin D deficiency and insufficiency are common in adolescents worldwide. Few data on vitamin D status and risk factors for hypovitaminosis D in Italian adolescents are currently available. METHODS: 25-hydroxyvitamin D (25-OH-D) and parathyroid hormone (PTH) levels were evaluated in 427 Italian healthy adolescents (10.0-21.0 years). We used the following cut-off of 25-OH-D to define vitamin D status: deficiency < 50 nmol/L; insufficiency 50-75 nmol/L; sufficiency ≥ 75 nmol/L. Hypovitaminosis D was defined as 25-OH-D levels < 75.0 nmol/L and severe vitamin D deficiency as 25-OH-D levels < 25.0 nmol/L. We evaluated gender, residence, season of blood withdrawal, ethnicity, weight status, sun exposure, use of sunscreens, outdoor physical activity, and history of fractures as predictors of vitamin D status. RESULTS: Enrolled adolescents had a median serum 25-OH-D level of 50.0 nmol/L, range 8.1-174.7, with 82.2% having hypovitaminosis D. Vitamin D deficiency and insufficiency were detected in 49.9% and 32.3% of adolescents, respectively. Among those with deficiency, 38 subjects were severely deficient (38/427, 8.9% of the entire sample). Non-white adolescents had a higher prevalence of severe vitamin D deficiency than white subjects (6/17-35.3% vs 32/410-7.8% respectively, p = 0.002). Logistic regression showed increased risk of hypovitaminosis D as follows: blood withdrawal taken in winter-spring (Odds ratio (OR) 5.64) compared to summer-fall period; overweight-obese adolescents (OR 3.89) compared to subjects with normal body mass index (BMI); low sun exposure (OR 5.94) compared to moderate-good exposure and regular use of sunscreens (OR 5.89) compared to non regular use. Adolescents who performed < 3 hours/week of outdoor exercise had higher prevalence of hypovitaminosis D. Gender, residence, and history of fractures were not associated with vitamin D status. Serum 25-OH-D levels were inversely related to PTH (r = -0.387, p < 0.0001) and BMI-SDS (r = -0.141, p = 0.007). 44/427 (10.3%) adolescents showed secondary hyperparathyroidism. CONCLUSIONS: Italian adolescents have high prevalence of vitamin D deficiency and insufficiency. Pediatricians should tackle predictors of vitamin D status, favoring a healthier lifestyle and promoting supplementation in the groups at higher risk of hypovitaminosis D.

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.

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.