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The vitamin D receptor (VDR) plays a critical role in the regulation of mineral and bone homeostasis. Upon binding of 1α,25-dihydroxyvitamin D 3 to the VDR, the activation function 2 (AF2) domain repositions and recruits coactivators for the assembly of the transcriptional machinery required for gene transcription. In contrast to coactivator-induced transcriptional activation, the functional effects of coactivator-independent VDR signaling remain unclear. In humans, mutations in the AF2 domain are associated with hereditary vitamin D-resistant rickets, a genetic disorder characterized by impaired bone mineralization and growth. In the present study, we used mice with a systemic or conditional deletion of the VDR-AF2 domain (Vdr ΔAF2 ) to study coactivator-independent VDR signaling. We confirm that ligand-induced transcriptional activation was disabled because the mutant VDR ΔAF2 protein was unable to interact with coactivators. Systemic Vdr ΔAF2 mice developed short, undermineralized bones with dysmorphic growth plates, a bone phenotype that was more pronounced than that of systemic Vdr knockout (Vdr -/- ) mice. Interestingly, a rescue diet that is high in calcium, phosphate, and lactose, normalized this phenotype in Vdr -/- , but not in Vdr ΔAF2 mice. However, osteoblast- and osteoclast-specific Vdr ΔAF2 mice did not recapitulate this bone phenotype indicating coactivator-independent VDR effects are more important in other organs. In addition, RNA-sequencing analysis of duodenum and kidney revealed a decreased expression of VDR target genes in systemic Vdr ΔAF2 mice, which was not observed in Vdr -/- mice. These genes could provide new insights in the compensatory (re)absorption of minerals that are crucial for bone homeostasis. In summary, coactivator-independent VDR effects contribute to mineral and bone homeostasis., (© 2024. The Author(s).)

Vitamin D 3 deficiency and insufficiency are becoming a common global issue for us, especially in the most industrially developed countries. The only acknowledged activity of vitamin D 3 in vertebrates is to promote the absorption of calcium and, therefore, allow for the mineralization of bones. Accordingly, its deficiency is associated with diseases such as rickets. Other numerous vital functions associated with vitamin D 3 are yet to be considered, and the function of vitamin D 2 in plants is unknown. Thus, 100 years after its discovery, the importance of vitamin D still seems to be unacknowledged (except for rickets), with little attention given to its decrease throughout the world. In this review, I suggest that vitamin D deficiency and insufficiency may be linked to the westernized lifestyle in more developed countries. Furthermore, I suggest that, rather than the calcemic activity, the main function of vitamin D is, in general, that of strengthening living organisms. I conclude with the hypothesis that vitamin D deficiency may represent a marker for a greater risk of chronic inflammatory diseases and a shorter life expectancy.

Background: The role of maternal vitamin D supplementation in the prevention of infantile rickets is unknown, particularly in low- and middle-income countries without routine infant vitamin D supplementation. Through secondary analysis of a randomized, placebo-controlled trial in Bangladesh, we examined the dose-ranging effects of maternal vitamin D supplementation on the risk of biochemical rickets at 6 to 12 months of age., Methods: Pregnant women (n = 1300) were randomized into 5 groups: placebo, or vitamin D 4200 IU/week, 16 800 IU/week, or 28 000 IU/week from second trimester to delivery and placebo until 6 months postpartum; or 28 000 IU/week prenatally and until 6 months postpartum. Infants underwent biochemical rickets screening from 6 to 12 months of age (n = 790). Relative risks (RR) and 95% confidence intervals (95% CI) of biochemical rickets were estimated for each group versus placebo., Results: Overall, 39/790 (4.9%) infants had biochemical rickets. Prevalence was highest in the placebo group (7.8%), and the risk was significantly lower among infants whose mothers received combined prenatal and postpartum vitamin D at 28 000 IU/week (1.3%; RR, 0.16; 95% CI, 0.03-0.72). Risks among infants whose mothers received only prenatal supplementation (4200 IU, 16 800 IU, 28 000 IU weekly) were not significantly different from placebo: 3.8% (RR, 0.48; 95% CI, 0.19-1.22), 5.8% (RR, 0.74; 95% CI, 0.33-1.69), and 5.7% (RR, 0.73; 95% CI, 0.32-1.65), respectively., Conclusions: Maternal vitamin D supplementation (28 000 IU/week) during the third trimester of pregnancy until 6 months postpartum reduced the risk of infantile biochemical rickets. Further research is needed to define optimal postpartum supplementation dosing during lactation.

Purpose: The objective of this systematic review was to determine a minimum serum 25-hydroxyvitamin D (25OHD) threshold based on the risk of having rickets in young children. This work was commissioned by the WHO and FAO within the framework of the update of the vitamin D requirements for children 0-3 years old., Methods: A systematic search of Embase was conducted to identify studies involving children below  4 years of age with serum 25OHD levels and radiologically confirmed rickets, without any restriction related to the geographical location or language. Study-level and individual participant data (IPD)-level random effects multi-level meta-analyses were conducted. The odds, sensitivity and specificity for rickets at different serum 25OHD thresholds were calculated for all children as well as for children with adequate calcium intakes only., Results: A total of 120 studies with 5412 participants were included. At the study-level, children with rickets had a mean serum 25OHD of 23 nmol/L (95% CI 19-27). At the IPD level, children with rickets had a median and mean serum 25OHD of 23 and 29 nmol/L, respectively. More than half (55%) of the children with rickets had serum 25OHD below 25 nmol/L, 62% below 30 nmol/L, and 79% below 40 nmol/L. Analysis of odds, sensitivities and specificities for nutritional rickets at different serum 25OHD thresholds suggested a minimal risk threshold of around 28 nmol/L for children with adequate calcium intakes and 40 nmol/L for children with low calcium intakes., Conclusion: This systematic review and IPD meta-analysis suggests that from a public health perspective and to inform the development of dietary requirements for vitamin D, a minimum serum 25OHD threshold of around 28 nmol/L and above would represent a low risk of nutritional rickets for the majority of children with an adequate calcium intake., (© 2024. The Author(s).)

Background & objectives Globally, vitamin D deficiency has been incriminated in poor bone health and growth retardation in children, impaired adult musculoskeletal health (classically described), increased risk of cardiovascular events, immune dysfunction, neurologic disorders, insulin resistance and its multiple sequelae, polycystic ovary syndrome (PCOS) and certain cancers. This review intends to holistically highlight the burden of vitamin D deficiency among children in India, the public health importance, and potential therapeutic and preventive options, utilizing the concept of implementation research. Methods A systematic search was carried out on PubMed, Embase, China National Knowledge Infrastructure (CNKI) and Cochrane database, clinicaltrials.gov, Google Scholar, and ctri.nic.in with the keywords or MeSH terms namely 'vitamin D', 'cholecalciferol', 'ergocalciferol', 'children', connected with appropriate boolean operators. Results Vitamin D deficiency/insufficiency prevalence varies from 70-90 per cent in Indian children. Rickets, stunting, impaired bone mineral health, and dental health are common problems in these children. Serum 25-hydroxy vitamin D (25(OH)D) should be maintained >20 ng/ml in children. Oral vitamin D supplementation has a high therapeutic window (1200-10,000 IU/d well tolerated). Fortification of grains, cereal, milk, bread, fruit juice, yogurt, and cheese with vitamin D has been tried in different countries across the globe. From Indian perspective, fortification of food items which is virtually used by everyone would be ideal like fortified milk or cooking oil. Fortification of "laddus" made from "Bengal gram" with vitamin D as a part of a mid-day meal programme for children can be an option. Interpretation & conclusions There is enough evidence from India to suggest the importance and utility of food fortification with vitamin D to address the epidemic of vitamin D deficiency/insufficiency in children.

Historically vitamin D deficiency had devastating consequences for children causing rickets resulting in severe bone deformities often leading to death. The mystery of the cause of rickets finally came to light when it was observed that cod liver oil and sunlight could prevent and cure rickets. The first vitamin D to be discovered was vitamin D 2 from ergosterol in ultraviolet irradiated yeast. Vitamin D 3 was discovered from UV exposure to the skin. Investigations revealed the two major functions of vitamin D were to increase intestinal calcium and phosphate absorption and mobilize calcium from the skeleton to maintain calcium and phosphorus homeostasis. Later studies demonstrated that vitamin D does not have an active role in bone mineralization. Vitamin D deficiency results in secondary hyperparathyroidism increasing bone resorption. As a result, this decreases bone mineral content and compromises the architectural integrity increasing risk for fracture. Vitamin D deficiency has also been shown to enhance aging of the bone causing cracks and enhancing bone fractures. Vitamin D deficiency also causes osteomalacia. Therefore, vitamin D sufficiency is extremely important to maximize bone health throughout life. It helps to prevent bone loss, but it cannot restore bone loss due to increased bone resorption that can occur under a variety of circumstances including menopause. The Endocrine Society Guidelines recommends for all ages that adequate vitamin D obtained from the sun, foods and supplements is necessary in order to maintain a circulating concentration of 25-hydroxyvitamin D of at least 30 ng/mL for maximum bone health., (Copyright © 2024. Published by Elsevier Inc.)

Abstract: Nutritional rickets is the failure of normal bone formation in children, caused by vitamin D deficiency, low calcium intake, or a combination of both. In the United States, prolonged breastfeeding without vitamin D supplementation is a major risk factor. Increasing awareness of the rationale for and importance of vitamin D supplements for all breastfed infants and children should reduce the incidence of vitamin D deficiency rickets and prevent bone deformity., (Copyright © 2023 American Academy of Physician Associates.)

Vitamin D deficiency is prevalent among various groups in the UK, and can result from insufficient sunlight exposure and dietary intake. There is a population-wide recommendation of 10 micrograms (400 international units) of vitamin D per day, with a daily supplement advised. However, supplement use is often suboptimal, compounding the risk of deficiency. Long-term vitamin D deficiency can cause rickets in children and osteomalacia or osteoporosis in adults. Therefore, it is important that nurses recognise which groups are at increased risk of vitamin D deficiency and understand how to assess people's vitamin D status. Nurses also need to be able to support the prevention and treatment of low vitamin D levels, which typically involves supplementation and lifestyle changes., Competing Interests: None declared, (© 2023 RCN Publishing Company Ltd. All rights reserved. Not to be copied, transmitted or recorded in any way, in whole or part, without prior permission of the publishers.)

Vitamin D plays a vital role in regulating calcium and phosphate metabolism and maintaining bone health. A state of prolonged or profound vitamin D deficiency (VDD) can result in rickets in children and osteomalacia in children and adults. Recent studies have demonstrated the pleiotropic action of vitamin D and identified its effects on multiple biological processes in addition to bone health. VDD is more prevalent in chronic childhood conditions such as long-standing systemic illnesses affecting the renal, liver, gastrointestinal, skin, neurologic and musculoskeletal systems. VDD superimposed on the underlying disease process and treatments that can adversely affect bone turnover can all add to the disease burden in these groups of children. The current review outlines the causes and mechanisms underlying poor bone health in certain groups of children and young people with chronic diseases with an emphasis on the proactive screening and treatment of VDD.

Introduction: Rates of infant vitamin D supplementation fall short of guideline recommendations. We explored this discrepancy from the clinician perspective as they advise and affect this important intervention to prevent rickets. We compared infant and high-dose maternal vitamin D supplementation prescribing attitudes and practices between infant-only clinicians (IC) and clinicians who care for mothers and infants (MIC)., Methods: We surveyed clinicians in departments of family medicine, obstetrics/gynecology, primary care pediatrics, neonatology, newborn nursery, and members of vitamin D and rickets working groups and a social media group for lactation medicine providers about their perspectives and practices regarding vitamin D supplementation., Results: 360 clinician survey responses were analyzed. In current practice, IC were more likely than MIC to recommend vitamin D supplementation to exclusively ( P < .001 ) and partially breastfed infants ( P = .005 ). MIC were more likely than IC to discuss infant and high-dose maternal supplementation options and let the parents/caregivers choose (34.7%, 22.0%, P = .009 ). If supplementing the mother with high-dose vitamin D or the infant directly each provided adequate vitamin D in the infant, MIC were more likely than IC to think that supplementation of the mother would be preferred by parents/caregivers (63.0%, 45.2%, P = .003 ), improve adherence (66.5%, 49.4%, P = .006 ), and promote breastfeeding (54.7%, 36.5%, P = .001 ); they were also more likely to recommend supplementation of the mother (17.7%, 8.9%, P = .04 )., Conclusions: MIC are more likely than IC to embrace high-dose maternal vitamin D supplementation to provide adequate vitamin D for infants. This highlights an opportunity for further education of clinicians about this option., Competing Interests: Conflict of interest: None., (© Copyright by the American Board of Family Medicine.)

Background: Nutritional rickets (NR) is still a major problem and is exacerbated by an increasing influx of immigrants. In this study, Turkish and immigrant cases followed with the diagnosis of NR in our pediatric endocrinology clinic were retrospectively evaluated., Methods: Detailed data of cases diagnosed with NR between 2013 and 2020 and followed for at least six months were reviewed., Results: In the study period, 77 cases of NR were identified. Turkish children constituted 76.6% (n=59) while 18 (23.4%) were immigrant children. The mean age at diagnosis was 8.1±7.8 months, 32.5% (n=25) were female, and 67.5% (n=52) were male. The 25-hydroxyvitamin D3 was below normal in all patients, with a mean value of 4.3±2.6 ng/mL. Parathyroid hormone (PTH) was above normal in all and the mean value was 301.7±139.3 pg/ mL. While there were 3.9 cases of NR in 10,000 endocrine clinic patients in 2013, this rate increased more than four-fold to 15.7 patients in 2019., Conclusions: Despite the vitamin D prophylaxis program in Türkiye, NR is seen significantly more frequently in recent years, which may be associated with an increasing number of refugees. High PTH levels indicate the severity of NR cases admitted to our clinic. However, clinically significant NR is only the tip of the iceberg and the true burden of subclinical rickets is unknown. Increasing compliance with the vitamin D supplementation program in refugee and Turkish children is important for the prevention of nutritional rickets.

Background: Early childhood rickets increased in Alaska Native children after decreases in vitamin D-rich subsistence diet in childbearing-aged women. We evaluated the impact of routine prenatal vitamin D supplementation initiated in Alaska’s Yukon Kuskokwim Delta in Fall 2016. Methods: We queried electronic health records of prenatal women with 25(OH) vitamin D testing during the period 2015−2019. We evaluated 25(OH)D concentrations, vitamin D3 supplement refills, and decayed, missing, and filled teeth (dmft) scores and rickets in offspring. Results: Mean 25(OH)D concentrations increased 36.5% from pre- to post-supplementation; the percentage with deficient 25(OH)D decreased by 66.4%. Women with ≥ 60 vitamin D3 refill days had higher late pregnancy 25(OH)D concentrations than those with no refill days (p < 0.0001). Women with late pregnancy insufficient 25(OH)D concentrations had offspring with higher dmft scores than those with sufficient 25(OH)D (RR 1.3, p < 0.0001). Three children were diagnosed with nutritional rickets during the period 2001−2021, and none after 2017. Conclusions: These findings suggest that prenatal vitamin D supplementation can improve childhood outcomes in high-risk populations with high rates of rickets.

This open-label, block-randomized controlled trial compared the effect of 800 IU/day and 400 IU/day of oral vitamin D 3 supplementation in reducing vitamin D insufficiency (VDI) among healthy-term breastfed infants at 14 weeks of postnatal age. All eligible infants were randomized to receive either 800 or 400 IU/day of oral vitamin D 3 (starting within the first week until 14 weeks). The primary outcome was the proportion of infants with VDI (25-OH-D < 20 ng/ml) at 14 weeks. Secondary outcomes were vitamin D deficiency (VDD, < 12 ng/ml), severe VDD (< 5 ng/ml), anthropometry, biochemical or clinical rickets, and any adverse events related to vitamin D toxicity (VDT). Among 102 enrolled infants, the distribution of baseline variables (including cord 25-OH-D levels; 13.0 versus 14.2 ng/ml) was similar in both groups. On intention-to-treat analysis, the proportions of infants with VDI at 14 weeks were significantly lower in the 800 IU group compared to those in the 400 IU group [24% versus 55%; RR 0.44; 95% CI: 0.25-0.76]. The proportions of infants with elevated parathormone (6% versus 26.5%; p = 0.012) and severe VDD (0% versus 12.2%; p = 0.033) were significantly lower in the 800 IU group. Clinical rickets developed in three (6.2%) infants in the 400 IU group. No infant developed VDT.      Conclusions: Daily oral supplementation with 800 IU of vitamin D 3 resulted in an almost 50% reduction in the proportion of infants with VDI and prevented the occurrence of severe VDD at 14 weeks of age compared to 400 IU with no evidence of vitamin D toxicity.     Trial Registration: Clinical Trial Registry of India (CTRI/2019/02/017374). What is Known: • Breastfeeding is the ideal source of nutrition for healthy-term breastfed infants; however, vitamin D content of breastmilk is suboptimal. • AAP recommends daily oral supplementation of 400 IU of vitamin D to all healthy-term breastfed infants; however, trials from high-income countries support insufficiency of this dose in maintaining serum 25-OH-D levels >20 ng/ml with no such information from low-middle-income countries. What is New: • 800 IU/day of oral vitamin D3 supplementation among term breastfed infants significantly reduces vitamin D insufficiency at 14 weeks' age as compared to the recommended dose of 400 IU/day. • This higher supplemental dose is safe with no evidence of vitamin D toxicity., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Vitamin D is essential for the normal mineralization of bones during childhood. Although diet and adequate sun exposure should provide enough of this nutrient, there is a high prevalence of vitamin D deficiency rickets worldwide. Children with certain conditions that lead to decreased vitamin D production and/or absorption are at the greatest risk of nutritional rickets. In addition, several rare genetic alterations are also associated with severe forms of vitamin-D-resistant or -dependent rickets. Although vitamin D3 is the threshold nutrient for the vitamin D endocrine system (VDES), direct measurement of circulating vitamin D3 itself is not a good marker of the nutritional status of the system. Calcifediol (or 25(OH)D) serum levels are used to assess VDES status. While there is no clear consensus among the different scientific associations on calcifediol status, many clinical trials have demonstrated the benefit of ensuring normal 25(OH)D serum levels and calcium intake for the prevention or treatment of nutritional rickets in childhood. Therefore, during the first year of life, infants should receive vitamin D treatment with at least 400 IU/day. In addition, a diet should ensure a normal calcium intake. Healthy lifestyle habits to prevent vitamin D deficiency should be encouraged during childhood. In children who develop clinical signs of rickets, adequate treatment with vitamin D and calcium should be guaranteed. Children with additional risk factors for 25(OH)D deficiency and nutritional rickets should be assessed periodically and treated promptly to prevent further bone damage.

Justification: The emerging literature on prevalence of vitamin D deficiency in India, prevention and treatment strategies of rickets, and extra-skeletal benefits of vitamin D suggest the need for revising the existing guidelines for prevention and treatment of vitamin D deficiency in India., Objectives: To review the emerging literature on vitamin D prevalence and need for universal vitamin D supplementation. To suggest optimum vitamin D therapy for treatment of asymptomatic and symptomatic vitamin D deficiency, and rickets. To evaluate the extra-skeletal health benefits of vitamin D in children., Process: A National consultative committee was formed that comprised of clinicians, epidemiologists, endocrinologists, and nutritionists. The Committee conducted deliberations on different aspects of vitamin D deficiency and rickets through ten online meetings between March and September, 2021. A draft guideline was formulated, which was reviewed and approved by all Committee members., Recommendations: The group reiterates the serum 25-hydroxy vitamin D cutoffs proposed for vitamin D deficiency, insufficiency, and sufficiency as <12 ng/mL, 12-20 ng/mL and >20 ng/mL, respectively. Vitamin D toxicity is defined as serum 25OHD >100 ng/mL with hypercalcemia and/or hypercalciuria. Vitamin D supplementation in doses of 400 IU/day is recommended during infancy; however, the estimated average requirement in older children and adolescents (400-600 IU/day, respectively) should be met from diet and natural sources like sunlight. Rickets and vitamin D deficiency should be treated with oral cholecalciferol, preferably in a daily dosing schedule (2000 IU below 1 year of age and 3000 IU in older children) for 12 weeks. If compliance to daily dosing cannot be ensured, intermittent regimens may be prescribed for children above 6 months of age. Universal vitamin D supplementation is not recommended in childhood pneumonia, diarrhea, tuberculosis, HIV and non-infectious conditions like asthma, atopic dermatitis, and developmental disorders. Serum 25-hydroxy vitamin D level of >20 ng/mL should be maintained in children with conditions at high-risk for vitamin deficiency, like nephrotic syndrome, chronic liver disease, chronic renal failure, and intake of anticonvulsants or glucocorticoids.

Kurt Huldschinsky (1883-1940) was a German pediatrician who was one of the international leaders in the field of rickets research between the two world wars. After his medical studies, he served at the Kaiserin-Auguste-Victoria-Haus in Berlin and at the University Children's Hospital in Vienna, among other places. After World War I, he worked with the famous orthopedist Konrad Biesalski at the Oskar-Helene-Heim for the healing and education of frail children in Berlin. Here he was the first to prove that exposure to ultraviolet (UV) radiation from mercury vapor lamps ("artificial sunlight") could cure rickets in young children, which is mostly caused by vitamin D deficiency. He published his discovery in this journal - the Deutsche Medizinische Wochenschrift [German Medical Weekly] - in 1919. For this groundbreaking scientific achievement and his further research into the prevention and treatment of rickets, Huldschinsky was awarded the Otto Heubner Prize of the German Association of Pediatrics in 1926. He was even nominated for the Nobel Prize in Medicine. As a Jew, however, he had to flee Germany from the National Socialists in 1933/34. Together with his wife and daughter, he emigrated to Egypt, where he died in Alexandria on October 31, 1940. As Huldschinsky was for many decades almost forgotten, this article recalls the life and work of a meritorious physician and scientist., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)

Objectives: Nutritional rickets (NR) is still an important problem and one which increasing influxes of immigrants are further exacerbating. This study evaluated cases of mostly immigrant children followed up with diagnoses of NR in our pediatric endocrinology clinic., Methods: Details of 20 cases diagnosed with NR between 2017 and 2020 were retrieved from file records., Results: Twenty (11 male) cases were included in the study. Three (15%) were Turkish nationals and the others (85%) were immigrants. Hypocalcemia and hypophosphatemia were detected in 17 and 13, respectively. Alkaline phosphatase (ALP) values were normal in two cases, while ALP and parathyroid hormone (PTH) values were elevated in all other cases, and PTH levels were very high (473.64 ± 197.05 pg/mL). 25-hydroxyvitamin D levels were below 20 ng/mL in all cases. Patients with NR received high-dose long-term vitamin D or stoss therapy. Six patients failed to attend long-term follow-up, while PTH and ALP levels and clinical findings improved at long-term follow-up in the other 14 cases., Conclusions: The elevated PTH levels suggest only the most severe cases of NR presented to our clinic. Clinically evident NR is therefore only the tip of the iceberg, and the true burden of subclinical rickets and osteomalacia remains unidentified. Public health policies should therefore focus on universal vitamin D supplementation and adequate dietary calcium provision, their integration into child surveillance programs, adequate advice and support to ensure normal nutrition, exposure to sunlight, and informing families of the increased risk not only for resident populations but also for refugee and immigrant children., (© 2021 Walter de Gruyter GmbH, Berlin/Boston.)

We looked at existing recommendations and supporting evidence on the effectiveness of vitamin D supplementation in infancy for reducing vitamin D deficiency and for preventing rickets and infections. We also looked at optimal dose of vitamin D and the age until which vitamin D supplementation is beneficial.We conducted a literature search up to the 17th of July 2019 by using key terms and manual search in selected sources. We summarized the recommendations and the strength of the recommendation when and as reported by the authors. We summarized the main findings of systematic reviews with the certainty of the evidence as reported.A daily dose of 400 international units of vitamin D in infants has shown to be effective for improving bone health and preventing rickets. Evidence is more robust in groups of infants and children at risk. Vitamin D supplementation is well tolerated, and not associated with toxicity. Higher doses have not shown to add benefit while it could potentially cause toxic blood levels and hypercalcemia. Adequate levels of vitamin D might not be achieved with lower daily doses. Universal vitamin D supplementation starting shortly after birth, regardless of the mode of feeding and until 12 months of age, is strongly recommended. Beyond 12 months of age vitamin D supplementation is recommended only in groups of children at risk., (© 2021. The Author(s).)

Background: Severe prolonged vitamin D deficiency can cause rickets or osteomalacia. Both can be prevented by sunshine exposure or vitamin D supplementation. Although New Zealand guidance does not recommend vitamin D supplementation for the general population, it can be considered for individuals at risk of vitamin D deficiency. Routine measurement of 25-hydroxyvitamin D (25OHD) is also considered unnecessary., Methods: We investigated the rates of vitamin D supplementation, rickets and osteomalacia in New Zealand, and of 25OHD results in Auckland, over the last two decades., Results: Vitamin D prescriptions increased 14-fold, from 86,295/year to 1,215,507/year, between 2003 and 2019, with medication costs alone in 2019 being >$1 million. Despite these changes, the annual prevalence of hospital admissions for rickets, osteomalacia and unspecified vitamin D deficiency remained low and stable (10-20/year). 25OHD concentrations increased between 2002 and 2003 and between 2009 and 2019, and in the later time-period, 25OHD tests mainly identified individuals without vitamin D deficiency (40-50% >75nmol/L, 65-70% >50nmol/L and only 7-12.5% <25nmol/L)., Conclusions: Osteomalacia and rickets persist at low rates despite widespread, increasingly costly vitamin D supplementation and testing, which largely identifies individuals without vitamin D deficiency. These results suggest that vitamin D guidance and practice in New Zealand should change., Competing Interests: None of the authors have any financial conflicts of interest, but all authors have co-authored randomised controlled trials and systematic reviews of the efficacy of vitamin D supplements and co-authored articles concluding that there is no role for routine vitamin D supplementation in community dwelling individuals.

Background: Nutritional rickets is believed to result from the interaction of inadequate serum 25-hydroxyvitamin D [25(OH)D] concentration and dietary calcium intake, but this interaction has not been confirmed in children with rickets. Determining the vitamin D requirements to prevent nutritional rickets has been thwarted by inconsistent case definition, inadequate adjustment for calcium intake and other confounders, and 25(OH)D assay variability., Objectives: To model the 25(OH)D concentration associated with nutritional rickets in calcium-deprived Nigerian children, adjusted for confounding factors, and develop a general approach to define vitamin D status while accounting for calcium intake., Methods: Logistic regression was used to model the association of serum 25(OH)D with having rickets adjusted for calcium intake in a reanalysis of a case-control study in Nigerian children. The matching variables age, sex, weight-for-age z score, and 4 additional significant variables were selected [religion, age began walking, phosphorus intake, and the 25(OH)D × calcium intake interaction] using a rigorous 7-step algorithm., Results: Cases had significantly (P < 0.0001) lower mean ± SD 25(OH)D than controls (33 ± 13 compared with 51 ± 16 nmol/L, respectively), whereas cases and controls had similarly (P = 0.81) low mean dietary calcium intakes (216 ± 88 and 213 ± 95 mg/d, respectively). There was a significant interaction between 25(OH)D and calcium intake [coefficient (95% CI): -0.0006 (-0.0009, -0.0002)]. Accordingly, as calcium intake increased from 130 to 300 mg/d, the adjusted odds of having rickets decreased dramatically with increasing 25(OH)D such that at 200 mg/d, the adjusted odds of having rickets at 47.5 nmol/L was 0.80, whereas it was 0.2 at 62.5 nmol/L. Moreover, at a calcium intake of 300 mg/d, the adjusted odds was 0.16 at a 25(OH)D concentration of 47.5 nmol/L and 0.02 at 62.5 nmol/L., Conclusions: The vitamin D requirement to prevent nutritional rickets varies inversely with calcium intake and vice versa. Also, application of multivariable modeling is essential in defining vitamin D requirements., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.)

The value of vitamin D supplementation in the treatment or prevention of various conditions is often viewed with scepticism as a result of contradictory results of randomised trials. It is now becoming apparent that there is a pattern to these inconsistencies. A recent large trial has shown that high-dose intermittent bolus vitamin D therapy is ineffective at preventing rickets - the condition that is most unequivocally caused by vitamin D deficiency. There is a plausible biological explanation since high-dose bolus replacement induces long-term expression of the catabolic enzyme 24-hydroxylase and fibroblast growth factor 23, both of which have vitamin D inactivating effects. Meta-analyses of vitamin D supplementation in prevention of acute respiratory infection and trials in tuberculosis and other conditions also support efficacy of low dose daily maintenance rather than intermittent bolus dosing. This is particularly relevant during the current COVID-19 pandemic given the well-documented associations between COVID-19 risk and vitamin D deficiency. We would urge that clinicians take note of these findings and give strong support to widespread use of daily vitamin D supplementation., (© Royal College of Physicians 2021. All rights reserved.)

Background and Objectives: Vitamin D is essential for healthy development of bones, but little is known about the effects of supplementation in young stunted children. Our objective was to assess the effect of vitamin D supplementation on risk of rickets and linear growth among Afghan children., Methods: In this double-blind, placebo-controlled trial, 3046 children ages 1 to 11 months from inner-city Kabul were randomly assigned to receive oral vitamin D 3 (100 000 IU) or placebo every 3 months for 18 months. Rickets Severity Score was calculated by using wrist and knee radiographs for 631 randomly selected infants at 18 months, and rickets was defined as a score >1.5. Weight and length were measured at baseline and 18 months by using standard techniques, and z scores were calculated., Results: Mean (95% confidence interval [CI]) serum 25-hydroxyvitamin D (seasonally corrected) and dietary calcium intake were insufficient at 37 (35-39) nmol/L and 372 (327-418) mg/day, respectively. Prevalence of rickets was 5.5% (placebo) and 5.3% (vitamin D): odds ratio 0.96 (95% CI: 0.48 to 1.92); P = .9. The mean difference in height-for-age z score was 0.05 (95% CI: -0.05 to 0.15), P = .3, although the effect of vitamin D was greater for those consuming >300 mg/day of dietary calcium (0.14 [95% CI: 0 to 0.29]; P = .05). There were no between-group differences in weight-for-age or weight-for-height z scores., Conclusions: Except in those with higher calcium intake, vitamin D supplementation had no effect on rickets or growth., Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2021 by the American Academy of Pediatrics.)

Competing Interests: CM and PS are members of the advisory board for Kyowa Kirin and have received speaker fees. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

The study aimed to estimate vitamin D intake and plasma/serum 25-hydroxyvitamin D (25(OH)D) concentrations, investigate determinants of 25(OH)D concentrations and compare two 25(OH)D assays. We conducted two nationwide cross-sectional studies in Sweden with 206 school children aged 10-12 years and 1797 adults aged 18-80 years ( n 268 provided blood samples). A web-based dietary record was used to assess dietary intake. Plasma/serum 25(OH)D was analysed by liquid chromatography-mass spectrometry (LC-MS) and immunoassay in adults and LC-MS/MS in children. Most participants reported a vitamin D intake below the average requirement (AR), 16 % of children and 33 % of adults met the AR (7⋅5 μg). In adults, plasma 25(OH)D below 30 and 50 nmol/l were found in 1 and 18 % of participants during the summer period and in 9 and 40 % of participants during the winter period, respectively. In children, serum 25(OH)D below 30 and 50 nmol/l were found in 5 and 42 % of participants (samples collected March-May), respectively. Higher 25(OH)D concentrations were associated with the summer season, vacations in sunny locations (adults), and dietary intake of vitamin D and use of vitamin D supplements, while lower concentrations were associated with a higher BMI and an origin outside of Europe. Concentrations of 25(OH)D were lower using the immunoassay than with the LC-MS assay, but associations with dietary factors and seasonal variability were similar. In conclusion, vitamin D intake was lower than the AR, especially in children. The 25(OH)D concentrations were low in many participants, but few participants had a concentration below 30 nmol/l., (© The Author(s) 2020.)

Background: Rickets is a common disease worldwide. In the developed world, its prevalence dramatically decreased but still diagnosed in at-risk populations. The skin plays a critical role in vitamin D synthesis. Therefore, several skin diseases, especially keratinization disorders, could lead to impaired vitamin D metabolism and vitamin D deficient rickets., Objective: The article aimed to summarize the current knowledge of skin diseases and conditions associated with rickets., Methods: To examine the association between rickets and skin diseases, we performed a systematic review of the literature using PubMed database. The search included studies published from the database inception to August 2019., Results: A total number of 75 articles were included. Identified conditions associated with rickets were ichthyosis being a more common skin diseases, alopecia, epidermal and melanocytic nevi, xeroderma pigmentosum, mastocytosis, psoriasis, and atopic dermatitis. Three types of rickets were identified: vitamin D-dependent rickets, hypocalcemic vitamin D-dependent rickets type 2, and hypophosphatemic rickets. Cutaneous skeletal hypophosphatemia syndrome is a newly described and under-recognized condition. It is defined by the association of epidermal or melanocytic nevi, hypophosphatemic rickets, and elevated levels of fibroblast growth factor 23. Rickets in patients with ichthyosis was mainly due to impaired ability of ichthyotic skin to synthesize vitamin D, poor UV penetration of the skin caused by keratinocyte proliferation, and dark phototype. The latter may be considered a risk factor for rickets in patients with ichthyosis., Conclusion: Despite its rarity, these associations should be properly recognized by dermatologists. Early diagnosis of rickets is important to prevent growth retardation and skeletal deformities., (© 2020 John Wiley & Sons A/S . Published by John Wiley & Sons Ltd.)

In 2016, a global consensus on the prevention, diagnosis and management of nutritional rickets was published. The bone and mineral working group of the Australasian Paediatric Endocrine Group provides a summary and highlights differences to previous Australian and New Zealand (ANZ) guidelines on vitamin D deficiency and their implications for clinicians. Key points are: (i) The International Consensus document is focused on nutritional rickets, whereas the ANZ guidelines were focused on vitamin D deficiency. (ii) Definitions for the interpretation of 25-hydroxy vitamin D (25OHD) levels do not differ between statements. (iii) The global consensus recommends that routine 25OHD screening should not be performed in healthy children and recommendations for vitamin D supplementation are not based solely on 25OHD levels. The Australasian Paediatric Endocrine Group bone and mineral working group supports that screening for vitamin D deficiency should be restricted to populations at risk. (iv) Recommendations from the global consensus for vitamin D dosages for the therapy of nutritional rickets (diagnosed based on history, physical examination, biochemical testing and a confirmation by X-rays) are higher than in ANZ publications. (v) The global consensus recommends the implementation of public health strategies such as universal supplementation with vitamin D from birth to 1 year of age and food fortification. We conclude that updated global recommendations for therapy of nutritional rickets complement previously published position statements for Australia and New Zealand. Screening, management and the implementation of public health strategies need to be further explored for Australia., (© 2020 Paediatrics and Child Health Division (The Royal Australasian College of Physicians).)

Fortification of food products with vitamin D was central to the eradication of rickets in the early parts of the 20th century in the United States. In the subsequent almost 100 years since, accumulating evidence has linked vitamin D deficiency to a variety of outcomes, and this has paralleled greater public interest and awareness of the health benefits of vitamin D. Supplements containing vitamin D are now widely available in both industrialized and developing countries, and many are in the form of unregulated formulations sold to the public with little guidance for safe administration. Together, this has contributed to a transition whereby a dramatic global increase in cases of vitamin D toxicity has been reported. Clinicians are now faced with the challenge of managing this condition that can present on a spectrum from asymptomatic to acute life-threatening complications. This article considers contemporary data on vitamin D toxicity, and diagnostic and management strategies relevant to clinical practice.

Rickets was first described in great detail in the mid 17th century and was affecting a great number of children in major European cities. The disease, however, existed already in the Roman times. The etiology of this disease remained enigmatic until the 1920s when two different mechanisms, lack of exposure to sunlight and lack of a dietary factor were finally solved by the discovery of vitamin D and its dual origin. Soon thereafter, the implementation of vitamin D supplementation for all infants and small children largely eliminated nutritional rickets in Europe and North America. It took nearly a century to elucidate the complex chemistry, metabolism, mode and spectrum of activity of the vitamin D endocrine system. Nutritional rickets, whether due to simple vitamin D or calcium deficiency or both, remains widely ravaging many infants and children around the world. Asian countries and the Middle East are mainly confronted with vitamin D deficiency whereas many African and some Asian countries face calcium deficiency rickets. Immigrants and refugees or in general people with a darker skin living in moderate climate zone are also confronted with this disease. There is great consensus how this disease could be prevented or cured. In collaboration with most international professional societies, we prepare a memorandum, in line with the successful battle against iodine deficiency disorders, to convince the World Health Organization and its member states to start an implementation program to eradicate nutritional rickets by 2030., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: Vitamin D supplementation is known to both prevent and treat rickets, a disease of hypomineralized bone. Childhood is a period of great bone development and, therefore, attention to the vitamin D needed to optimize bone health in childhood is imperative., Summary: Observational studies have pointed to a vitamin D status, as indicated by a 25-hydroxyvitamin D concentration, of 50 nmol/L to ensure avoidance of rickets and of 75 nmol/L to optimize health. However, the benefits of achieving these levels of vitamin D status are less evident when pediatric randomized, controlled trials are performed. In fact, no specific pediatric vitamin D supplementation has been established by the existing evidence. Yet, study of vitamin D physiology continues to uncover further potential benefits to vitamin D sufficiency. This disconnection between vitamin D function and trials of supplementation has led to new paths of investigation, including establishment of the best method to measure vitamin D status, examination of genetic variation in vitamin D metabolism, and consideration that vitamin D status is a marker of another variable, such as physical activity, and its association with bone health. Nevertheless, vitamin D supplementation in the range of 10-50 μg/day appears to be safe for children and remains a promising intervention that may yet be supported by clinical trials as a method to optimize pediatric health. Key Message: Pediatric vitamin D status is associated with avoidance of rickets. Randomized, controlled trials of vitamin D supplementation for pediatric bone health are limited and equivocal in their results. Beyond bone, decreased risk for autoimmune, infectious, and allergic diseases has been associated with higher vitamin D status. The specific vitamin D supplementation to optimize toddler, child, and adolescent outcomes is unknown, but doses 10-50 μg/day are safe and may be beneficial., (© 2020 S. Karger AG, Basel.)

The aim of this article is to correct a very general error in scientific articles, in textbooks and in the Internet that has become an accepted fact. In this literature, the term "vitamin E″ is used for several similar molecules (both tocopherols and tocotrienols) that have never been shown to have vitamin property, i.e. a protective effect against the human deficiency disease. In fact, the name "vitamin E″ should only be used to define molecules that prevent the human deficiency disease "Ataxia with Vitamin E Deficiency" (AVED). Only one such molecule is known, α-tocopherol. This error may confuse consumers as well as medical doctors, who prescribe vitamin E without realizing that the current use of the name includes molecules of unknown, if not unwanted functions., (Copyright © 2019 The Author. Published by Elsevier B.V. All rights reserved.)

The etiology of endemic rickets was discovered a century ago. Vitamin D is the precursor of 25-hydroxyvitamin D and other metabolites, including 1,25(OH)2D, the ligand for the vitamin D receptor (VDR). The effects of the vitamin D endocrine system on bone and its growth plate are primarily indirect and mediated by its effect on intestinal calcium transport and serum calcium and phosphate homeostasis. Rickets and osteomalacia can be prevented by daily supplements of 400 IU of vitamin D. Vitamin D deficiency (serum 25-hydroxyvitamin D <50 nmol/L) accelerates bone turnover, bone loss, and osteoporotic fractures. These risks can be reduced by 800 IU of vitamin D together with an appropriate calcium intake, given to institutionalized or vitamin D-deficient elderly subjects. VDR and vitamin D metabolic enzymes are widely expressed. Numerous genetic, molecular, cellular, and animal studies strongly suggest that vitamin D signaling has many extraskeletal effects. These include regulation of cell proliferation, immune and muscle function, skin differentiation, and reproduction, as well as vascular and metabolic properties. From observational studies in human subjects, poor vitamin D status is associated with nearly all diseases predicted by these extraskeletal actions. Results of randomized controlled trials and Mendelian randomization studies are supportive of vitamin D supplementation in reducing the incidence of some diseases, but, globally, conclusions are mixed. These findings point to a need for continued ongoing and future basic and clinical studies to better define whether vitamin D status can be optimized to improve many aspects of human health. Vitamin D deficiency enhances the risk of osteoporotic fractures and is associated with many diseases. We review what is established and what is plausible regarding the health effects of vitamin D., (Copyright © 2019 Endocrine Society.)

Problem: No consensus on vitamin D deficiency (VDD) screening in children and adolescents exists. Early VDD detection can improve the health of children. VDD can cause bone mineralization diseases, such as rickets in children. The purpose of this review is to determine existing VDD screening recommendations or clinical practice guidelines in children and adolescents., Eligibility Criteria: Inclusion criteria were VDD screening 'guideline', 'clinical practice guideline', and 'recommendations' for children and adolescents in English, published 2001-2018., Results: Eight current guidelines addressed VDD screening recommendations with the common recommendation results endorsing screening only for VDD in at-risk children and adolescents., Conclusions: There is insufficient evidence for pediatric healthcare providers to recommend which VDD risk factors should be utilized for screening in children and adolescents., Implications: Further studies should focus on developing a validated VDD screening tool for children and adolescents based on risk factors., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Ensuring that the entire Australian population is Vitamin D sufficient is challenging, given the wide range of latitudes spanned by the country, its multicultural population and highly urbanised lifestyle of the majority of its population. Specific issues related to the unique aspects of vitamin D metabolism during pregnancy and infancy further complicate how best to develop a universally safe and effective public health policy to ensure vitamin D adequacy for all. Furthermore, as Australia is considered a "sunny country", it does not yet have a national vitamin D food supplementation policy. Rickets remains very uncommon in Australian infants and children, however it has been recognised for decades that infants of newly arrived immigrants remain particularly at risk. Yet vitamin D deficiency rickets is entirely preventable, with the caveat that when rickets occurs in the absence of preexisting risk factors and/or is poorly responsive to adequate treatment, consideration needs to be given to genetic forms of rickets.

Objective: Maternal vitamin D deficiency is an important risk factor that causes infantile rickets in the neonatal and infantile period. The aim of this study was to review the prevalence, clinical characteristics, and treatment of vitamin D deficiency and the follow-ups with infants and their mothers by the neonatal intensive care unit of Afiyet Hospital in Turkey., Methods: Calcium (Ca), phosphorus (P) and 25 (OH) vitamin D were studied and prospectively recorded in infants and their mothers detected to have hypocalcemia during routine biochemistry tests performed on the third postnatal day of the patients follow up and treated with different diagnoses., Results: A total of 2,460 infants were admitted into the neonatal intensive care unit between August 2014 and January 2018. Of the infants included in the study, 324 (66.1%) were male and 166 (33.8%) were female, and 366 (74.6%) of them had been delivered by cesarean section (C/S), 124 (25.3%) of them had been delivered by Normal Spontaneous Delivery (NSD). Hypocalcemia was detected in 490 (19.9%) of the infants. In a total of 190 (38.7%) infants and 86 mothers (17.5%), the levels of 25 (OH) vitamin D were found to be below the laboratory detection limit of <3 ng/ml. When vitamin D deficiency + insufficiency is assessed by season, 151 of them were found to be in summer (30.99%), 118 in spring (24.18%), 117 in the winter season(23.87%), and 93 in autumn(18.97%), respectively. There was a statistically significant positive correlation of 78.7% between the vitamins D values of the mothers and the infants (p: 0.000, p<0.05)., Conclusion: This study conducted that a positive correlation of between the vitamin D values of the mothers and the infants. In order to prevent maternal vitamin D deficiency, the appropriate dose of prophylaxis providing optimal levels of vitamin D and should be given by according to the levels of 25 (OH) D vitamin during pregnancy., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

The consequences of vitamin D and dietary calcium deficiency have become a huge public health concern in the UK. The burden of disease from these deficiencies includes rickets, and hypocalcaemic seizures, dilated cardiomyopathy and mostly occult myopathy and osteomalacia. The increasing burden of the disease is intrinsically linked to ethnicity and the population demographic changes in the UK. Three facts have led to the resurfacing of the English disease: (1) the UK has no ultraviolet sunlight for at least 6 months of the year, (2) dark skin produces far less vitamin D than white skin per unit ultraviolet light exposure, and (3) non-European Union immigration over the last century. To date, the UK government demonstrates incomplete understanding of these three facts, and its failure to adjust its prevention programmes to changing demographics is endangering the health and life of UK residents with dark skin, of whom infants are the most vulnerable. Establishing accountability through the implementation of monitored antenatal and infantile supplementation programmes and mandatory food fortification is overdue., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Hypovitaminosis D has become a pandemic, being observed in all ethnicities and age groups worldwide. Environmental factors, such as increased air pollution and reduced ultraviolet B (UVB) irradiation, as well as lifestyle factors, i.e., decreased outdoor activities and/or poor intake of vitamin D-rich food, are likely involved in the etiology of a dramatic reduction of vitamin D circulating levels. The insufficiency/deficiency of vitamin D has long been known for its association with osteoporosis and rickets. However, in the last few decades it has become a serious public health concern since it has been shown to be independently associated with various chronic pathological conditions such as cancer, coronary heart disease, neurological diseases, type II diabetes, autoimmune diseases, depression, with various inflammatory disorders, and with increased risk for all-cause mortality in the general population. Prevention strategies for these disorders have recently involved supplementation with either vitamin D2 or vitamin D3 or their analogs at required daily doses and tolerable upper-limit levels. This review will focus on the emerging evidence about non-classical biological functions of vitamin D in various disorders., Competing Interests: The authors declare no conflict of interest.

Vitamin D and calcium in the human milk is essential for the growth and the prevention of rickets in infants. In this review, we will discuss the physiology and the functions of vitamin D and calcium and the mechanisms of vitamin D and calcium transfer into the human breast milk. This review describes the recommended intake of vitamin D and calcium for infants and lactating mothers and the factors influencing the content of vitamin D and calcium in human milk. Furthermore, the measurement of vitamin D compounds and calcium in human breast milk is described in this review., (Copyright © 2018. Published by Elsevier Ltd.)

Purpose of Review: Nutritional rickets and osteomalacia are common in dark-skinned and migrant populations. Their global incidence is rising due to changing population demographics, failing prevention policies and missing implementation strategies. The calcium deprivation spectrum has hypocalcaemic (seizures, tetany and dilated cardiomyopathy) and late hypophosphataemic (rickets, osteomalacia and muscle weakness) complications. This article reviews sustainable prevention strategies and identifies areas for future research., Recent Findings: The global rickets consensus recognises the equal contribution of vitamin D and dietary calcium in the causation of calcium deprivation and provides a three stage categorisation for sufficiency, insufficiency and deficiency. For rickets prevention, 400 IU daily is recommended for all infants from birth and 600 IU in pregnancy, alongside monitoring in antenatal and child health surveillance programmes. High-risk populations require lifelong supplementation and food fortification with vitamin D or calcium. Future research should identify the true prevalence of rickets and osteomalacia, their role in bone fragility and infant mortality, and best screening and public health prevention tools.

Background: Vitamin D supplementation is widely recommended for infants, but the optimal dose remains unclear. High intake may result in hypercalcemia., Methods: We evaluated the incidence of hypercalcemia during the first year of life in a cohort of 987 healthy children who received 10 or 30 μg of vitamin D3 supplementation daily. Ionized calcium (Ca-ion) was analyzed at 6 and 12 months, and serum 25-hydroxyvitamin D (25-OHD) and parathyroid hormone (PTH) concentration at 12 months. Severe hypercalcemia was defined as Ca-ion exceeding the reference limit (1.16-1.39 mmol/L) by 10%., Results: No severe hypercalcemia occurred. Mild hypercalcemia (1.40-1.52 mmol/L) was present at 6 months in 28% and at 12 months in 2% of infants. At 12 months, 25-OHD ranged between 23 and 241 nmol/L (median 97), and PTH was between undetectable and 104 pg/mL (median 24) and was below the reference range (11.5-78.4 pg/mL) in 11%. 25-OHD and Ca-ion correlated positively (r = 0.149), and 25-OHD was slightly higher in the 12 infants with mild hypercalcemia (median 97 vs. 110 nmol/L, p = 0.046)., Conclusions: Vitamin D3 supplementation of 10 or 30 µg did not cause severe hypercalcemia. Mild hypercalcemia was more prevalent at 6 months than at 12 months, and was associated weakly with 25-OHD at 12 months., (© 2017 S. Karger AG, Basel.)

Nutritional rickets continues to be a significant health problem for children worldwide with recent evidence of increasing incidence in many developed countries. It is due to vitamin D deficiency and/or inadequate dietary calcium intake with variation in the relative contributions of each of these dependant on environmental factors such a dietary intake and sunlight exposure. Key to the prevention of rickets is ensuring that pregnant women and their infants receive vitamin D supplementation with good evidence from randomised controlled trials that infants who receive 400iu daily can achieve levels of 25 hydroxyvitamin D of >50nmol/l. However, public health implementation of daily supplementation is more challenging with a need to revisit food fortification strategies to ensure optimal vitamin D status of the population. Treatment of nutritional rickets has traditionally been with vitamin D2 or D3, often given as a daily oral dose for several weeks until biochemical and radiological evidence of healing. However, other treatment regimes with single or intermittent high doses have also proved to be effective. It is now recognised that oral calcium either as dietary intake or supplements should be routinely used in conjunction with vitamin D for treatment., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: Vitamin D and calcium deficiencies are common worldwide, causing nutritional rickets and osteomalacia, which have a major impact on health, growth, and development of infants, children, and adolescents; the consequences can be lethal or can last into adulthood. The goals of this evidence-based consensus document are to provide health care professionals with guidance for prevention, diagnosis, and management of nutritional rickets and to provide policy makers with a framework to work toward its eradication., Evidence: A systematic literature search examining the definition, diagnosis, treatment, and prevention of nutritional rickets in children was conducted. Evidence-based recommendations were developed using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system that describe the strength of the recommendation and the quality of supporting evidence., Process: Thirty-three nominated experts in pediatric endocrinology, pediatrics, nutrition, epidemiology, public health, and health economics evaluated the evidence on specific questions within five working groups. The consensus group, representing 11 international scientific organizations, participated in a multiday conference in May 2014 to reach a global evidence-based consensus., Results: This consensus document defines nutritional rickets and its diagnostic criteria and describes the clinical management of rickets and osteomalacia. Risk factors, particularly in mothers and infants, are ranked, and specific prevention recommendations including food fortification and supplementation are offered for both the clinical and public health contexts., Conclusion: Rickets, osteomalacia, and vitamin D and calcium deficiencies are preventable global public health problems in infants, children, and adolescents. Implementation of international rickets prevention programs, including supplementation and food fortification, is urgently required.