Vitamin D Supplementation Guidelines for General Population and Groups at Risk of Vitamin D Deficiency in Poland-Recommendations of the Polish Society of Pediatric Endocrinology and Diabetes and the Expert Panel With Participation of National Specialist Consultants and Representatives of Scientific Societies-2018 Update.

INTRODUCTION: Vitamin D deficiency is an important public health problem worldwide. Vitamin D deficiency confers a significant risk for both skeletal and non-skeletal disorders and a number of lifelong negative health outcomes. The objectives of this evidence-based guidelines document are to provide health care professionals in Poland, an updated recommendation for the prevention, diagnosis and treatment of vitamin D deficiency. METHODS: A systematic literature search examining the prevention and treatment strategies for vitamin D deficiency was conducted. Updated recommendations were developed using the Grading of Recommendations, Assessment, Development and Evaluation system describing the strength of the recommendation and the quality of supporting evidence. Twenty-seven contributors representing different areas of expertise and medical specialties, including pediatricians, geriatricians, endocrinologists, epidemiologists, nephrologists, gynecologists and obstetricians evaluated the available published evidence related to vitamin D, formulated the goals of this document and developed a common consolidated position. The consensus group, representing six national specialist consultants and eight Polish and international scientific organizations/societies, participated in the process of grading evidence and drawing up the general and specific recommendations. RESULTS: The updated recommendations define the diagnostic criteria for the evaluation of vitamin D status and describe the prevention and treatment strategies of vitamin D deficiency in the general population and in groups at increased risk of the deficiency. Age- and weight-specific recommendations for prevention, supplementation and treatment of vitamin D deficiency are presented, and detailed practice guidance is discussed regarding the management in primary and specialized health care. CONCLUSION: Vitamin D deficiency remains still highly prevalent in Poland, in all age groups. Currently, there is a great necessity to implement a regular supplementation with recommended doses and to develop an effective strategy to alleviate vitamin D deficiency in the population. These updated recommendations are addressed to health professionals and the authorities pursuing comprehensive health policies and should also be included in public health programs aimed at preventing a broad spectrum of chronic diseases.

Recurrent fractures as a new skeletal problem in the course of Angelman syndrome.

Angelman syndrome is a genetically inherited syndrome with severe retardation of psychomotor development and speech disturbances, usually accompanied by epilepsy, typical dysmorphic features, and some skeletal symptoms. The aim of the current report is to present new skeletal symptoms which may occur in the course of AS, based on a case report of an 8-year-old girl with confirmed 15q11;12 microdeletion and recurrent low-trauma bone fractures. According to our knowledge it is the first report of such skeletal symptoms in patient with a diagnosis of AS.

[Brittle bone disease type III in neonates--own experience]. / Wrodzona lamliwosc kosci typu III u noworodków--obserwacje wlasne.

UNLABELLED: Fractures of long bone and ribs in the neonatal period may be expression of genetic disturbances of collagen type I production. The aim of the study was to present clinical symptoms, results of radiological, biochemical and densitometric examinations in 11 newborns with osteogenesis imperfecta type III. METHODS: In all children accurate medical history, clinical examination and radiograph were performed. We measured concentration of 25-hydroxyvitamin D (25OHD) and osteocalcin (bone formation marker) in serum. Urinary excretion of bone resorption marker type I collagen N-telopeptide related to creatinine were made. In 5/11 children densitometric examination in Infant programme by DXA method (dual-X-ray absorptiometry) were done. RESULTS: In all family osteogenesis imperfecta occurred by the first. In clinical examination deformities in body proportion, shortness of the extremities, sabre shanks, flabbily of skull bones and reduction of activity were diagnosed. 8/11 newborns had blue sclera. In all X-ray (baby-gram) bone fractures occurring in utero as well as after birth were founded. In biochemical indices a small numbers of abnormality were described. In 5/11 newborns with results of densitometric examination normal bone mineral density adequate to body mass were demonstrated, in 3/5 bone mineral content (BMC) were decreased. CONCLUSION: 1.Osteogens esis imperfecta is the one of reasons of bone fractures in neonates and its diagnosis is based on family history, clinical manifestation and X-ray examination. 2. In newborns with bone fractures dual X-ray absorptiometry are recomendated.

Proteomic analysis of plasma profiles in children with recurrent bone fractures.

UNLABELLED: The aim of the study is proteomic analysis of the plasma profile in children with recurrent bone fractures. The study involved 16 children: 6 patients with recurrent low-energy fractures and normal bone mass and 10 with osteogenesis imperfecta. In the analysis of the protein profile, the two-dimensional protein electrophoresis was used (Ettan DALT II, Amersham Bioscience). The images of protein gels were compared with controls. The protein spots with changed expression were cut from the gel and the amino acid sequence was analyzed with the mass spectrometry method (Q-Tof Premier(TM) API MASS SPECTROMETR, Waters) for protein identification. The most prevalent protein with changed expression, with respect to controls, was haptoglobin observed in 6 patients with a severe form of osteogenesis imperfecta. Increased haptoglobin concentration in these patients was confirmed by the ELISA method. Peptides corresponding to alpha-1 acid glycoprotein and serum amyloid P-component, apolipoprotein A-I, and transthyretin were detected in one, two and three children, respectively. CONCLUSIONS: 1) The results show increased haptoglobin which may be suggestive of an inflammatory component taking part in the course of osteogenesis imperfecta. 2) Further studies to explain the possible relationship of this protein with increased bone fragility are necessary.

[The vitamin D and calcium consumption and bone quality in children of lódZ (Poland) at the age 9-13 years]. / Spozycie witaminy D i wapnia a jakosc kosci dzieci lódzkich w wieku 9-13 lat.

INTRODUCTION: Only few publications concern the influence of the vitamin D and calcium consumption on the bone mineralization in the developmental age. AIM OF THE STUDY: The aim of the study was the analysis of the vitamin D and calcium diet supply in relation to the bone status assessed with Quantitative Ultrasound (QUS) in growing children. MATERIAL AND METHODS: The study comprised 643 pupils (384 girls and 259 boys) at the age 9-13 years from primary schools in lódZ. The medium daily consumption of vitamin D and calcium was estimated with the computer program Dieta 2. In all children the QUS was performed. RESULTS: Extreme deficiency of vitamin D was found in the diet of nearly all examined children (in 96,7% schoolgirls and 95,7% schoolboys). Girls consumed on average 25,5% of recommended values, boys 33,3%. Considerable deficiency of diet calcium was observed in 92% schoolgirls and 81,9% of schoolboys. The medium daily consumption of calcium was higher than vitamin D and reached 59,2% of recommended values in girls and 66,2% in boys. In 48% of children an decrease of at least one of the QUS parameters was observed. The statistical analysis showed positive, significant correlation between QUS parameters and calcium consumption, it was not observed for vitamin D. CONCLUSIONS: 1. The deficiency of diet vitamin D and calcium is common in children in lódZ. 2. The extremely low supply of diet vitamin D does not meet the recommended values. 3. The lowering of the QUS parameters observed in 48% of children indicates for worse bone mineralization and bone quality. 4. The results of this study indicate for the necessity of changes in nutritional habits of children and adolescence and if it is not possible the supplementation of vitamin D and calcium.

Evaluation of bone mineral density and bone metabolism in children with multiple bone fractures.

BACKGROUND: The aim of the study was to carry out a comprehensive analysis of determinants of multiple bone fractures in children with regard to densitometric indices and markers of bone metabolism. MATERIAL AND METHODS: The study involved 112 children aged 5-18 years, including 81 patients with a history of at least 3 bone fractures and 31 healthy patients in a control group. Total body and spinal DXA densitometry of the skeleton (DPX-L apparatus, Lunar) was carried out in all children. Laboratory assays comprised the determination of calcium, phosphorus, magnesium (in the serum and 24-hour urine collection), parathormone, liver metabolite of vitamin D, osteocalcin, bone alkaline phosphatase, and N-terminal cross-linked telopeptide of collagen type I (NTx). RESULTS: Mean values of DXA Z-score, both in total body and in spinal scans, were significantly lower in children with multiple fractures as compared to controls. In children with multiple fractures, there was a higher prevalence of hypercalciuria, hypermagnesuria and hyperphosphaturia. Decreased levels of the liver metabolite of vitamin D were observed in 20/81 (24.7%) patients in this group and in 6/31 controls. Other findings included a higher level of NTx in 38/75 (50.7%) patients with fractures, an increased activity of bone alkaline phosphatase in 29, and of osteocalcin in 12 patients. In this group, there was a significant negative correlation between biochemical bone turnover markers and low bone mass. Also, lower DXA Z-scores were found in children with higher urinary calcium excretion. CONCLUSIONS: 1. Decreased bone mineral density was the most frequent risk factor for bone fractures in children; it was found in about 2/3 of the patients with multiple bone fractures. 2. Accelerated bone turnover, and, particularly, increased bone resorption, indicates a derangement of bone metabolism in children with multiple fractures. 3. Repeated fractures during the body growth period are an indication for a quantitative evaluation of bone mass, calcium-phosphate metabolism and bone turnover markers.

Insulin-like growth factor-I and mineral metabolism markers in children with idiopathic decrease in bone mass.

OBJECTIVE: The aim of the study was to determine whether the serum concentration of insulin-like growth factor-I (IGF-I) and its binding protein-3 (IGFBP-3) correlates with the mineral metabolism markers in children with idiopathic decrease in bone mass. PATIENTS AND METHODS: The study comprised 62 patients aged 6-18 years, including 42 with idiopathic decrease in bone mineral density (20 with osteoporosis and 22 with osteopenia) and 20 control children. Osteoporosis and osteopenia were diagnosed on the basis of complex clinical, densitometric and biochemical examinations (in all patients secondary causes of the decreased bone mass were excluded). Serum concentration of IGF-I was determined with radioimmunoassay and IGFBP-3 using immunoradiometry. RESULTS: The children with osteoporosis and osteopenia were found to have mean IGF-I concentration statistically significantly lower than the controls (548 and 645 v. 819 ng/ml, respectively; p<0.05). Moreover, IGF-I correlated positively with total and spinal bone mineral density. In children with osteoporosis there was also a significant relationship between IGF-I and pyridinoline and deoxypyridinoline in urine. CONCLUSIONS: Lower serum IGF-I concentration together with higher bone resorption and low bone mineral density reveal involvement of this growth factor in the development of idiopathic decrease of bone mass in children.

Evaluation of interleukin-1 and -6 in the etiopathogenesis of idiopathic osteoporosis and osteopenia in children.

INTRODUCTION: The aim of the study is to determine whether serum concentrations of interleukin (IL)-1and IL-6 correlate with indices of bone mineral metabolism in children with idiopathic osteoporosis and osteopenia. MATERIAL/METHODS: The study comprised 62 patients aged 6-18 years (20 with idiopathic osteoporosis, 22 with idiopathic osteopenia, and 20 controls). In 10 children, investigations were repeated after one year of treatment. Serum concentrations of IL-1alpha, IL-1beta, IL-1 receptor antagonist (IL-1ra), as well as IL-6 and its soluble receptor (IL-6sR) were determined by the ELISA method. In patients with decreased bone mass, selected calcium-phosphorus metabolism indices and bone turnover markers were assessed. RESULTS: Higher values of IL-6 were recorded in those with idiopathic osteoporosis than in controls (2.79 vs. 1.43; p<0.05). In these patients there was also a tendency towards higher values of IL-6sR (p=0.05). IL-1alpha and IL-1beta were not markedly elevated in any of the patients. No significant differences between groups regarding IL-1ra were observed. Negative correlation between IL-6, IL-1alpha, cytokine/receptor indices, and spinal bone mineral density was determined. Positive correlation was found between IL-alpha, IL-1/IL-1ra, and parathormon as well as between IL-1alpha, IL-6sR, and bone formation markers.markers. Increase in bone mass after treatment was accompanied by a decrease in IL-6sR. CONCLUSIONS: The higher serum levels of IL-6 in children with idiopathic osteoporosis/osteopenia and the decrease in IL-6sR after treatment reveal an involvement of IL-6 in the etiopathogenesis of these disturbances. The results suggest that IL-1 may also participate in the primary decrease of bone mass in children.

[Current views on the etiopathogenesis of idiopathic osteoporosis and osteopenia in the developmental period]. / Wspólczesne poglady na etiopatogeneze samoistnej osteoperozy i osteopenii w wieku rozwojowym.

The paper presents current literature review on the clinical features and possible etiopathogenetic factors in idiopathic osteoporosis and osteopenia in children and adolescents. Genetic and environmental factors determining bone mass growth are included. The effect of cytokines and hormones in the regulation of bone remodelling has been discussed in detail. Most recent studies have demonstrated that cytokines are involved in bone formation and resorption by their direct influence on the activity of osteoclasts and osteoblasts. In this way they affect the state of dynamic balance between the process of bone formation and resorption, and thus the mineralization of the skeleton.

[Treatment of osteoporosis and osteopenia in children--own experience]. / Leczenie osteoporozy i osteopenii u dzieci--doswiadczenia wlasne.

Osteoporosis and osteopenia diagnosed in developmental age require special treatment with careful consideration of indications for particular drugs, their dosage and monitoring of treatment. The classical method, similarly as in adults, is administration of calcium and vitamin D, physical rehabilitation, treatment of fractures and pain release. The aim of the study was to evaluate the effect of combined therapy of decreased bone mineralization in 45 children (28 boys and 17 girls) aged 6.5 to 18 years. In 15 of them secondary osteoporosis (13/15) or osteopenia (2/15) were diagnosed, and in 30 cases the disorders were primary -16/30 and 14/30, respectively. The patients were treated from 6 months to 4 years. All patients received calcium and vitamin D preparations. In the majority of treated children calcium-rich diet and physical rehabilitation were applied, adjusted to the advancement of the disease. In 6 cases treatment with bisphosphonates was given. In our study we also present results and observations from calcitonin treatment of 35 children aged 6 to 18 years. This treatment was applied during the last 5 years in various periods--in 23 children with secondary and in 12 with primary osteoporosis. The therapy of osteoporosis and osteopenia in developmental age should always be individually assessed to disease advancement, symptoms, concomitant illnesses, age and possibilities of long-term treatment. The classical treatment includes appropriate intake of calcium, vitamin D and other vitamins and minerals (pharmacological preparations, diet), physical rehabilitation and pain release. On the basis of our observations it appears that antiresorptive drugs such as calcitonin and bisphosphonates may be used in treatment of osteoporosis in developmental age. Evaluation of treatment efficacy should involve clinical improvement and results of additional examinations, especially densitometry. Among biochemical tests, bone resorption markers (Pyr, Dpyr, CrossLaps) appeared to be the most useful; treatment of bone fractures should be evaluated by X-ray examinations.