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Vitamin D is defined as a nutrient despite its rare occurrence in food. Vitamin D status is determined mainly by solar UV light action in skin. However, the strategy to combat vitamin D deficiency has been to increase oral intake of vitamin D in greater amounts than could be obtained from food. Persistent large intakes of vitamin D can cause hypercalcaemic toxicity. Although the amounts recommended to prevent deficiency are far less than those causing such toxicity, the possibility of other toxic actions from increased intake of vitamin D has been ignored. Animal experiments have demonstrated that moderate amounts of oral vitamin D over time result in atherosclerosis. Differences in the fate of vitamin D could explain this angiotoxicity.

Rickets is a disease that has been known to mankind for several decades. Overcoming this public health problem was a triumph of science and public policy in the 20th century, but over the course of several decades rickets sharply returned as a result of cultural, environmental and political factors. Vitamin D plays a fundamental role in the regulation of calcium and phosphorus homeostasis, and, consequently, in the development of rickets. In addition to these classic skeletal effects, recent studies have shown that vitamin D has other significant extracellular effects that can complicate the course of the disease and have long-term effects on children’s health. Vitamin D sufficiency in children has been defined as serum 25(OH) D levels of over 30 ng/ml, insufficiency as 21-30 ng/ml, deficiency as less than 20 ng/ml. The upper limit of the reference range is 100 nmol/L, as levels above may be associated with vitamin D toxicity in children. Serum 1.25(OH)2D should not be used for the assessment of vitamin D status. Natural sources of vitamin D are very limited, therefore, its use in the form of nutritional supplements is the primary mean of preventing and treating rickets. The recommended drug for the prevention and treatment of vitamin D deficiency is cholecalciferol (D3). Colecalciferol is recommended to be given at a dose of 1000 IU/day to all children aged 1 to 6 months regardless of the type of feeding or the season of the year to prevent vitamin D deficiency. This article presents modern ways of preventing, diagnosing and treating rickets.

Hypercalcemia is a common metabolic abnormality in children and generally occurs due to hyperparathyroidism, vitamin D toxicity, some genetic disorders and malignant diseases. Granulomatous diseases are a rare cause of hypercalcemia in children, which are usually mild and asymptomatic. Severe hypercalcemia in granulomatous diseases has also been reported in the literature. Here, we report a child presenting with severe hypercalcemia secondary to miliary tuberculosis with successful management with bisphosphonate treatment. Increased 1,25(OH)2D3 synthesis by activated macrophages in the granuloma tissue is the major mechanism of hypercalcemia in tuberculosis.

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. Resumo A suplementação de produtos alimentares com vitamina D foi fundamental para a erradicação do raquitismo no início do século XX nos Estados Unidos. Nos quase 100 anos subsequentes, o acúmulo de evidências vinculou a deficiência de vitamina D a uma variedade de desfechos, e isso tem levantado grande interesse público e conscientização dos benefícios à saúde da vitamina D. Os suplementos que contêm vitamina D estão agora amplamente disponíveis tanto nos países desenvolvidos quanto naqueles em desenvolvimento, e muitos estão na forma de formulações não regulamentadas, vendidas ao público com poucas orientações para uma administração segura. Juntos, isso contribuiu para uma transição na qual um aumento global dramático nos casos de toxicidade da vitamina D tem sido relatado. Médicos agora enfrentam o desafio de tratar essa condição que pode apresentar um espectro de complicações assintomáticas a agudas, com risco de vida. Este artigo considera dados atualizados sobre a toxicidade da vitamina D e estratégias de diagnóstico e manejo relevantes para a prática clínica.

Hypercalcemia is a frequently encountered electrolyte abnormality with a well-described differential diagnosis and classic algorithm for evaluation. The treatment for hypercalcemia is dependent on the underlying etiology. Hypervitaminosis D is an uncommon cause of hypercalcemia, but the use of vitamin D supplementation has expanded and case reports of supplemental vitamin D induced hypercalcemia have become more frequent. We present a case of hypervitaminosis D-induced altered mental status where diagnosis was delayed and additional invasive testing was performed due to an assumption regarding phosphatemia.

Background: Hypercalcemia is a common electrolyte abnormality presenting with a variety of symptoms. The common causes are primary hyperparathyroidism and malignancy associated with hypercalcemia. However, iatrogenic hypercalcemia with the overzealous use of vitamin D has now emerged as another important cause of hypercalcemia over the past decade. Objective: This study aims to evaluate the causes of hypercalcemia, management strategies, and outcomes in patients admitted with hypercalcemia in a tertiary care hospital. Method: It is a retrospective study done at Aga Khan University Hospital (AKUH), Karachi after taking approval from the ethical review committee (ERC). Data were gathered about all patients admitted from 1st January 2008 to 31st December 2018. A total of 1142 patients were included in the study and their calcium levels were noted. Along with demographic details, data pertaining to their diagnosis and all investigations done to evaluate the causes of hypercalcemia were noted in a pre-defined questionnaire. Results: A total of 814 patients having hypercalcemia were included in the final analysis and their mean age was 60.8 ± 14.1 years. Male and female patients were 45.4% and 54.6%, respectively, and their mean hospital stay was 6.2 ± 5.8 days. The most common cause of hypercalcemia was malignant solid tumors (49.1%), followed by hematological malignancy (16.5%), hyperparathyroidism (10.9%), definite vitamin D toxicity (8%), chronic kidney disease (4.9%), chronic granulomatous diseases (4.7%), and probable vitamin D toxicity (3.5%). The oral cavity carcinoma (17.7%) was the most common solid tumor associated with hypercalcemia. Amongst hematological malignancy, multiple myeloma (14.4%) was the most common one. Out of 814 patients admitted with hypercalcemia, 601 (74%) patients recovered from hypercalcemia, while mortality was observed in 129 (16%) patients. Of those who expired, 110 (85.3%) had malignancy either solid tumor or hematological. Conclusion: Malignancy is the most common cause of hypercalcemia in admitted patients. The knowledge of hypercalcemia’s causes is of great importance so that targeted investigations can be done. Not only will it minimize the cost burden and shorten the hospitalization of patients; it will also help the physicians to decide the appropriate management accordingly. Moreover, vitamin D toxicity was also observed in a significant number of patients which highlights the common practice of using higher doses of vitamin D by physicians.

Vitamin D intake over the recommended dose is usually associated with high serum 25(OH)D levels and generally not associated with symptoms of hypercalcemia. High doses of cholecalciferol need to be avoided to protect against vitamin D toxicity and related complications. Strict adherence to the clinical guidelines for treating vitamin D deficiency can ensure safe and effective treatment. We observed a tendency to use high doses of cholecalciferol for vitamin D deficiency treatment or vitamin D supplementation. We aimed to determine the biochemical characteristics of patients with high normal and elevated serum 25(OH)D levels. An online invitation was sent to all tertiary endocrinology clinics in Turkey to complete an online retrospective survey (DeVIT-TOX Survey) for patients diagnosed with high serum 25(OH)D levels (> 88 ng/mL) between January 2019 and December 2019. The patients were evaluated according to the presence of signs and symptoms of hypercalcemia and doses of vitamin D intake, evaluated into the following three groups according to their 25(OH)D levels: group 1, > 150 ng/mL; group 2, 149–100 ng/mL; and group 3, 99–88 ng/mL. A total of 253 patients were included in the final analysis (female/male: 215/38; mean age, 51.5 ± 15.6 years). The average serum 25(OH)D level was 119.9 ± 33 (range, 88–455) ng/mL, and the average serum calcium level was 9.8 ± 0.7 (range, 8.1–13.1) mg/dL. Most (n = 201; 75.4%) patients were asymptomatic despite having high serum 25(OH)D and calcium levels. The serum 25(OH)D level was significantly higher in the symptomatic groups than in the asymptomatic groups (138.6 ± 64 ng/mL vs. 117.7 ± 31 ng/mL, p

OBJECTIVE: Medical overuse leads to a burden on healthcare costs and potentially is harmful to patients. We wanted to address medical overuse in musculoskeletal disease and Rheumatology. METHODS: We performed a systemic literature review from Pubmed and Embase to study medical overuse. On the initial screen, 1499 studies were identified, 839 of them were related to medical overuse. Out of these, 52 were related to overuse in musculoskeletal diseases. Finally, 20 articles were chosen for this systemic review that reported overuse in Rheumatology. RESULTS: The article identifies issues with overtesting, including the use of dual-energy X-ray absorptiometry to screen for osteoporosis in women younger than 65 years old; and the use of magnetic resonance imaging to evaluate for osteoarthritis. Studies related to overtreatment, reported over-prescription of vitamin D supplements resulting in vitamin D toxicity; and increased risk of inappropriate prescriptions in patients with osteoarthritis and rheumatoid arthritis. Overtreating osteoporosis was reported after industry-sponsored education. Articles describing methods to reduce overuse included a study showing the reduction of unnecessary dual-energy X-ray absorptiometry scans after the introduction of the Choosing Wisely Campaign. CONCLUSIONS: Our findings suggest that there is some evidence that overtesting and overtreatment may be present in the field of rheumatology. This review aims to highlight this and help rheumatologists to be aware of overuse practices and provide appropriate evidence-based health care.

The growing awareness of the beneficial health effects of vitamin D supplementation, the commonality of vitamin D deficiency, and the over-the-counter availability of vitamin D supplements has resulted in a renewed interest in vitamin D supplementation among patients as well as health care providers. We present a case of vitamin D toxicity (VDT) in a patient following self-medication with mega doses that far exceeded the prescribed dosage. He presented to us with acute kidney injury (AKI) and elevated serum 25(OH)-vitamin D levels. He was treated with intravenous hydration, loop diuretics, and prednisone and had a clinical and biochemical improvement as reflected in his labs. We suggest that physicians and health care providers be made aware of this commonly overlooked side-effect of vitamin D supplementation and the importance of regular blood levels to titrate the dose accordingly. At the same time, it is important that the public is made aware of the ill-effects of self-medicating on large doses of vitamins.

About 50 million of the U.S. adult population suffer from chronic pain. It is a complex disease in its own right for which currently available analgesics have been deemed woefully inadequate since ~20% of the sufferers derive no benefit. Vitamin D, known for its role in calcium homeostasis and bone metabolism, is thought to be of clinical benefit in treating chronic pain without the side-effects of currently available analgesics. A strong correlation between hypovitaminosis D and incidence of bone pain is known. However, the potential underlying mechanisms by which vitamin D might exert its analgesic effects are poorly understood. In this review, we discuss pathways involved in pain sensing and processing primarily at the level of dorsal root ganglion (DRG) neurons and the potential interplay between vitamin D, its receptor (VDR) and known specific pain signaling pathways including nerve growth factor (NGF), glial-derived neurotrophic factor (GDNF), epidermal growth factor receptor (EGFR), and opioid receptors. We also discuss how vitamin D/VDR might influence immune cells and pain sensitization as well as review the increasingly important topic of vitamin D toxicity. Further in vitro and in vivo experimental studies will be required to study these potential interactions specifically in pain models. Such studies could highlight the potential usefulness of vitamin D either alone or in combination with existing analgesics to better treat chronic pain.

Background Vitamin D is an essential element for body health with its supplements generally administered to prevent vitamin D deficiency. Since these supplements are available in domestic settings, vitamin D toxicity may happen in children. Methods All children younger than 12 years who presented to the pediatric emergency department of Loghman Hakim Hospital, Tehran, Iran with history of ingestion of more than 1500 IU/day of vitamin D supplements were enrolled. Patients’ demographic data, on-presentation signs and symptoms, laboratory findings, treatments given, and outcome were evaluated. Result Fifteen patients presented during the study period. Their mean age was 46.53 ± 10.14 months and 12 (80%) were girls. All of them had unintentionally ingested vitamin D. Mean ingested dose was 406700.7 ± 227400.1 IU. In eight patients (53.3%), 25 hydroxy vitamin D level was more than 100 ng/mL. One patient experienced hypercalcemia while all of them were asymptomatic and discharged without complications. There was no significant difference between patients with and without high levels of 25 OH vitamin D regarding lab tests, toxicity course, and outcome. Conclusions It seems that acute vitamin D toxicity is a benign condition in our pediatric population which may be due to high prevalence of vitamin D deficiency in Iran.

In early 2000's vitamin-D deficiency was shown to be prevalent in several countries including the United States (US). Studies exploring the role of vitamin-D metabolism in diverse disease pathways generated an increased demand for vitamin-D supplementation and an immense public interest in measurement of vitamin-D metabolite levels. In this report, we review the role of vitamin-D metabolism in disease processes, clinical utility of measuring vitamin-D metabolites including 25-hydroxyvitamin-D (25(OH)D), 1,25-dihydroxyvitamin-D and 24,25-dihydroxyvitamin-D and discuss vitamin-D assay methodologies including immunoassays and liquid chromatography mass spectrometry (LC-MS/MS) assays. We also provide examples of vitamin-D toxicity and insight into the trends in serum 25(OH)D levels in the US population based on 10 years of data from on serum 25(OH)D values from ~5,000,000 patients who were tested at the Mayo Medical Laboratories between February 2007–February 2017. Keywords: Vitamin D supplementation trends, LC-MS/MS, Vitamin D toxicity

Vitamin D deficiency is an increasing problem affecting all ages. Patients should be assessed for risk factors as part of preventive health maintenance. Vitamin D toxicity is a rare occurrence caused by oversupplementation and errors in food fortification. The connection between vitamin D deficiency and osteoporosis, is well established. However, a cause and effect relationship has yet to be established between vitamin D deficiency and many chronic illnesses. An evidence-based approach is treating patients for an underlying vitamin D deficiency in hopes of improving many chronic illnesses.

Vitamin D is a particularly important sterol hormone, with evidence emerging of its beneficial effects well beyond bone. In consequence of this and increased global recognition of vitamin D deficiency in the general population, there has been a resurgence in treatment with vitamin D preparations. However, the increasing use of vitamin D treatments has also seen a substantial increase in the number of reports of vitamin D intoxication, with the majority (75%) of reports published since 2010. Many of these cases are a consequence of inappropriate prescribing, and the use of high‐dose over‐the‐counter preparations or unlicensed preparations. This review highlights that the majority of cases were preventable and discusses the inappropriate use of poorly formulated, and unlicensed vitamin D preparations.

Vitamin D is a fat-soluble vitamin essential for calcium homeostasis and bone health. Vitamin D toxicity or hypervitaminosis D is extremely rare. We describe the case of a 73-year-old man who presented with life-threatening hypervitaminosis D and hypercalcaemia resulting from self-medicated doses of vitamin D supplements. This case, alongside other global case reports, highlights the potential dangers of unlicensed vitamin D replacement. We discuss the evidence for vitamin D replacement and remind readers of the current guidance on daily intake and supplementation.

Background: Serum 25-hydroxyvitamin D (25(OH)D) assays have become readily available in India over the past decade. A large number of cross-sectional studies have been performed on the vitamin D status and the prevalence of vitamin D deficiency (VDD) in India. However, seasonal and long-term trends in serum 25(OH)D levels have been reported less frequently. Aim: To determine the seasonal and year-wise variation in vitamin D status at a tertiary care hospital in north India. Materials and Methods: Using hospital records, the data on serum 25(OH) D assays performed in its endocrinology laboratory between 2008 and 2016 were obtained. For analysis of seasonal trends, the months of a year were divided into following seasons: March to June (summer season), July to October (rainy season), and November to February (winter season). VDD was defined as serum 25(OH)D concentration 100 ng/mL) and vitamin D toxicity (serum 25(OH)D >150 ng/mL) were seen in 319 (1.2%) and 27 (0.1%) assays, respectively. Conclusions: This study provides data on seasonal and year-wise trends in vitamin D status over a long period of time at a tertiary care hospital in north India. A long-term trend toward improving vitamin D status, especially in females, was noted in the study. The prevalence of VDD was found to decrease in the analyzed samples during the study period.

We thank Charoenngam and colleagues for their prompt feedback[1][1] on the conclusions from our case study.[2][2] In light of their comments, it is important to provide further clarity. First, the observational studies and opinion pieces referenced by Charoenngam and colleagues examined acute

There are many reasons why the diagnosis of vitamin D toxicity in the recent case report by Auguste and colleagues[1][1] was probably wrong and the result of a red herring. The patient had been taking 8000–10 000 IU of vitamin D daily for 2.5 years, during which time serum creatinine levels were

The risk of vitamin D insufficiency in humans is a global problem that requires improving ways to increase vitamin D intake. Supplements are a primary means for increasing vitamin D intake, but without a clear consensus on what constitutes vitamin D sufficiency, there is toxicity risk with taking supplements. Chickens have been used in many vitamin D-related research studies, especially studies involving vitamin D supplementation. Our state-of-the-art review evaluates vitamin D metabolism and how the different hydroxylated forms are synthesized. We provide an overview with how vitamin D is absorbed, transported, excreted, and what tissues in the body store vitamin D metabolites. We also discuss a number of studies involving vitamin D supplementation with broilers and laying hens. Vitamin D deficiency and toxicity are also described and how they can be caused. The vitamin D receptor (VDR) is important for vitamin D metabolism. However, there is much more that can be understood with VDR in chickens. Potential research aims involving vitamin D and chickens should explore VDR mechanisms which could lead to newer insights with VDR. Utilizing chickens in future research to help with elucidating vitamin D mechanisms has great potential to advance human nutrition. Finding ways to increase vitamin D intake will be necessary because the coronavirus 2019 disease (COVID-19) pandemic is leading to increased risk of vitamin D deficiency in many populations. Chickens can provide a dual purpose with addressing pandemic-caused vitamin D deficiency: 1) vitamin D supplementation gives chickens added value with possibly leading to vitamin D-enriched meat and egg products; and 2) chickens’ use in research provides data for translational research. Expanding vitamin D-related research in chickens to include more nutritional aims in vitamin D status has great implications with developing better strategies to improve human health., Vitamin D research in chickens has important implications for advancing human nutrition, particularly with enriching vitamin D in meat products and eggs and better understanding vitamin D supplementation effects.

Background: Interest in the role of vitamin D in various physiological processes, the prevalence of its deficiency and importance of replacement has increased significantly over the past few decades. However, many formulations of vitamin D are not regulated and are available to the public without clear guidance on safe administration, which has contributed to the uptrend in the incidence and severity of vitamin D toxicity cases. Clinical Case A 57- year-old man with a medical history significant for amyotrophic lateral sclerosis, cervical myelopathy, and oropharyngeal dysphagia presented with weakness, constipation, polydipsia, polyuria and was found to have hypercalcemia with a total Calcium level of 15.5 mg/dL (n 8.6- 10.4), and albumin 4.2 g/dL (n 3.5–5.1). He soon developed acute hypoxic respiratory failure requiring prolonged intubation followed by tracheostomy. Evaluation of the hypercalcemia revealed an elevated 25-hydroxyvitamin D [25(OH)D] > 392 ng/mL (n 30–80), 1,25- dihydroxyvitamin D [1,25(OH)D] >600 pg/mL (n 19.9 - 79.3), PTH 8 pg/mL (n 12–88), and PTHrP 0.7 pmol/L (n< 4.2). The patient had initially stated that he was taking 5000 IU of vitamin D daily but further discussion with his wife revealed that he had been taking 2 teaspoons of a powder cholecalciferol preparation with 125 mcg (5000 IU of vitamin D) per 50 mg, which would be about 800,000 IU/day. He was treated with aggressive IV hydration, calcitonin and received 2 doses of pamidronate with an initial improvement in his Calcium level down to 10 mg/dL followed by recurrence of hypercalcemia. Work up for granulomatous disease and multiple myeloma revealed latent TB. At significantly elevated [25(OH)D] levels, toxicity is partially caused by the direct action of [25(OH)D] on the vitamin D receptor (VDR), and [25(OH)D] can also cross-react with the [1,25(OH)D] assay causing false elevation. Steroids were avoided because of his recent diagnosis of latent TB; hence he was started on Cinacalcet which was gradually increased to 60 mg twice a day with sustained Calcium normalization. Repeat labs showed improvement in [25(OH)D] to 292, and normalization of [1,25(OH)D] at 69.4. He was discharged on Cinacalcet 30 mg twice a day. Conclusion PTH-independent hypercalcemia is usually treated with hydration, anti-resorptive agents including bisphosphonates, denosumab and calcitonin, in addition to steroids in cases of increased 1 αλπηα-hydroxylase activity. Cinacalcet acts on the Calcium sensing receptor (CaSR) in parathyroid tissue, kidneys, bones and the intestine and was recently shown to improve hypercalcemia of malignancy in a report of 2 cases by Sheehan et al. Cinacalcet has helped our patient and might have a potential role for the prompt treatment of vitamin D toxicity, but more data is needed.

Vitamin D usage is becoming more and more common in the world with newer roles ascribed to it. The side effects of inadvertent overdose have been documented. Here, we present a case of Vitamin D toxicity who presented uniquely with quadriparesis.

Over the past two decades, vitamin D level measurements have become some of the most frequently ordered tests in the laboratory. This increase is due to a growing awareness of widespread vitamin D deficiency and scientific data suggesting the beneficial effects of vitamin D in various diseases. A literature search was carried out in PubMed for cases reporting vitamin D intoxication and overdose. Thirteen articles were included in this review. Intoxication was severe in the reported cases. Patients presented with serum vitamin D concentrations ranging between 150 and 1220 ng/mL and serum calcium concentrations between 11.1 and 23.1 mg/dL. Most of the reported patients showed symptoms of vitamin D toxicity such as vomiting, dehydration, pain, and loss of appetite. The underlying causes included manufacturing errors, overdosing by patients or prescribers, and combinations of these factors. Our literature search highlights the fact that even though vitamin D intoxication is rare, it does occur and therefore patients and prescribers should be more cognizant of the potential dangers of vitamin D overdose.

Background Interest in vitamin D has increased during the past 2 decades, with a corresponding increase in laboratory testing of 25-hydroxyvitamin D [25(OH)D]. The vast majority of specimens tested display normal or deficient levels of 25(OH)D; concentrations rarely fall in the potentially toxic range. Methods We performed a retrospective investigation of elevated 25(OH)D levels during a 16-year period at the University of Iowa Hospitals and Clinics (UIHC), a 734-bed tertiary-/quaternary-care academic medical center in the midwestern United States. Detailed medical-record review was performed for patients with serum/plasma 25(OH)D concentrations higher than 120 ng per mL. Results A total of 127,932 serum/plasma 25(OH)D measurements were performed on 73,779 unique patients. Of these patients, 780 (1.05%) had results that exceeded 80 ng per mL and 89 patients (0.12%) had results that exceeded 120 ng per mL. Only 4 patients showed symptoms of vitamin D toxicity. Three of these cases involved inadvertent misdosing of liquid formulations. Conclusions Symptomatic vitamin D toxicity is uncommon, and elevated levels of 25(OH)D do not strongly correlate with clinical symptoms or total serum/plasma calcium levels. Our study highlights the potential risks of the liquid formulation of vitamin D.

Vitamin D toxicity in infants is not uncommon, and has been reported as early as the 1930s, usually due to antirachitic treatment with very high doses of vitamin D. This usually involves administration of 600 000 IU vitamin D2 oral or intramuscularly (termed “stoss therapy”) resulting in vitamin D toxicity symptoms related to hypercalcemia.1-4 Most of these case reports occurred outside the United States. Recently, there are reports of vitamin D toxicity in very young breastfed infants, mostly in the United States, from inadvertent overdose with highly concentrated vitamin D formulation obtained over-the-counter or from free-standing stores (Table 1). Table 1. Case Reports of Breastfed Infants Who Had Vitamin D Toxicity.

In the case reported by Auguste and colleagues, [1][1] we believe that the patient experienced vitamin D intoxication because of an underlying pathologic condition that the authors failed to recognize. The authors incorrectly concluded that a dose of 8000–12 000 IU daily can result in vitamin D

Recommendation of vitamin D supplements is common although there is little information regarding the definition of the upper limit of safety. Kusunoki et al. now publish interesting data of a novel mechanism by which excess 25-hydroxyvitamin D exerts adverse effects on the kidney, using unilateral ureteral obstruction in the mouse as a model of kidney disease. Their report provides a new mechanism to be assessed as a surrogate measure of vitamin D toxicity that may be clinically relevant.

Osteoporosis is a skeletal disorder characterized by diminished bone strength, which results in an increased risk of fracture. Currently, osteoporosis is a public health priority due to the large number of individuals affected and the detrimental effect on quality of life. Primary osteoporosis, the most common form, usually results from age-related reduction in bone mineral strength. Over time, the individual's capacity to build bone is impaired, as the synthesis of vitamin D, the hormone responsible for calcium absorption, tends to decline. As serum calcium levels decrease, metabolic control serves to increase the removal of calcium from the skeleton to make up for the deficit. The synthesis of the 'hormone' vitamin D and its control therefore become central to intervention in involutional osteoporosis syndromes. In humans, plain vitamin D (cholecalciferol), also called parental or native vitamin D, is photosynthesized in the skin and then hydroxylated in the liver into the vitamin D analog calcidiol [25(OH)D3], which is hydroxylated again in the kidney into the vitamin D analog calcitriol [1,25(OH)2D3]. The advantage of administering vitamin D analogs is that the pro-drug calcidiol avoids the effect of declines in hepatic function, while calcitriol avoids the effect of declines in hepatic and kidney function. A strategy to enhance [25(OH)D3] levels to the optimal threshold of vitamin D is supplementation with the calcidiol metabolite itself. The goal of this paper is to review published studies on the efficacy of the calcidiol metabolite in increasing 25(OH)D3 serum levels and improving skeletal health parameters in humans.A library search of published papers in the area of use of calcidiol in humans from 1967 to 2013 was performed (key words: calcidiol, 25-hydroxy-vitamin D3, vitamin D supplementation, vitamin D metabolism, osteomalacia).The results of the survey made it possible to conclude that calcidiol is characterized by a number of features that make the compound ideal in conditions that require supplementation with a 25-hydroxylated metabolite.

Background: High prevalence of vitamin D deficiency (VDD) has been reported throughout the India for all age groups. Increased awareness about VDD among treating physicians has led to increased prescriptions of vitamin D preparations. Based on our experience of varied clinical and radiological response with different vitamin D formulations, we decided to assess cholecalciferol content of commonly available vitamin D formulations. Materials and Methods: We measured cholecalciferol content of 14 commercial preparations (two in the form of tablets and 12 as sachet) available in Indian market. Lab analysis was carried out in Shriram Institute for Industrial Research by high-performance liquid chromatography. Results: Of the total 14 samples analyzed only 4 (28.57%) were found to be within the acceptable ranges from −90 to +125% as defined by Indian Pharmacopia while 5 (35.7%) had higher and 5 (35.7%) had lower than the acceptable range. The percentage variation in cholecalciferol content as observed from the printed ranged widely from −91% to +65%. Conclusions: Our study shows a high degree of variability in cholecalciferol content of commercial preparations available in the Indian pharmaceutical market. This variation has many clinical implications as it may lead both, under treatment as well as vitamin D toxicity.

Inordinate administration of Vitamin D beyond required doses and duration occurs as a sporadic event among frequent empirical therapies of pharmacological Vitamin D. Such instances lead to Vitamin D intoxication. Systemic hypertension is an unsuspected after-effect of Vitamin D toxicity in a child unlike other toxicity effects such as hypercalcemia, neurological deterioration, etc., Here, we report a case of a 1-year-old child who developed acute hypertension and severe hypercalcemia due to Vitamin D toxicity which was masked by initial dehydration such as illness and brief review of literature about clinical entity.

Background: Vitamin D toxicity (VDT), a “not uncommon” cause of hypercalcemia, can be life-threatening and cause substantial morbidity, if not treated promptly. Aims: To describe presentation, management, and outcome in 32 patients with VDT diagnosed over 3 years. Materials and Methods: Patients presenting with VDT at a tertiary care centre in Srinagar Kashmir India were included. Evaluation included detailed history and biochemical tests including serum calcium, phosphate, creatinine, intact parathyroid hormone (iPTH), 25-hydroxy Vitamin D (25-OHD), and 24-hour urinary calcium. Results: The clinical manifestations of the 32 patients (median age 65; range 3–77 years) included gastrointestinal symptoms (constipation and vomiting), polyuria/polydipsia, altered sensorium, pancreatitis, acute kidney injury, and nephrocalcinosis. The median total serum calcium level was 13.95 (range 11.10-17.20) mg/dl and median 25-OHD level was 306 (range 105–2800) ng/ml. All patients had suppressed or low normal iPTH and hypercalciuria and 78% had azotemia. All patients had received multiple intramuscular injections of vitamin D3. The median cumulative dose was 4,200,000 (range, 1,800,000-30,000,000) IU. The median time to resolution of hypercalcemia was 7 months (range 4–18 months). Conclusion: We conclude that VDT is an increasingly common cause of symptomatic hypercalcemia. VDT needs prolonged follow up as it takes months to abate its toxicity. Enhancing awareness among general practitioners regarding the toxicity resulting from high doses of vitamin D is the key to prevent VDT. We suggest that VDT be considered in patients, especially the elderly, presenting with polyuria, polydispsia, vomiting, azotemia, or encephalopathy.

Summary Five cases of hypercalcaemia due to vitamin-D toxicity are described in horses. A brief survey of the literature on vitamin-D toxicity is given. Of the five horses, two were autopsied and had extensive mineralisation of the nonosseous tissues. Two other horses were treated and treatment was successful in one animal but not in the other. The fifth horse was destroyed by the owner. Zusammenfassung Hypercalzemie und Mineralisation der nicht-knochernen Gewebe bei Pferden infolge Vitamin-D-Vergiftung Funf Falle von Hyperkalzamie und Vitamin-D-Vergiftung bei Pferden sowie eine kurze Literaturubersicht uber Vitamin-D-Vergiftung werden beschrieben. Von den funf Pferden wurden zwei seziert und zeigten eine ausgedehnte Mineralisation der nichtknochernen Gewebe. Zwei Pferde wurden behandelt, das eine mit, das andere ohne Erfolg. Das funfte Pferd wurde durch den Besitzer getotet. Resume Hypercalcemie et mineralisation de tissus non osseux chez des chevaux a la suite d'une intoxication due a la vitamine D On decrit cinq cas d'hypercalcemie et d'intoxication a la vitamine D chez des chevaux et one donne un bref apercu de la litterature concernant l'empoisonnement a la vitamine D. Deux des cinq chevaux ont ete autopsies et ont montre une mineralisation etendue des tissus non osseux. On a traite deux chevaux, l'un avec succes, l'autre sans resultat. Le proprietaire a abattu le cinquieme cheval. Resumen Hipercalcemia y mineralizacion del tejido no oseo en caballos a consecuencia de intoxicacion por vitamina D Se describen cinco casos de hipercalcemia e intoxicacion vitaminica D en caballos, facilitandose tambien una revision bibliografica breve sobre la toxicidad de la vitamina D. De los cinco caballos se autopsiaron dos, los cuales mostraban una mineralizacion extensiva de los tejidos no oseos. Dos caballos fueron tratados, uno con, el otro sin exito. El quinto caballo fue matado por su propietario.

The serum 25-hydroxyvitamin D [25(OH)D] concentration that is the threshold for vitamin D toxicity has not been established. Hypercalcemia is the hazard criterion for vitamin D. Past policy of the Institute of Medicine has set the tolerable upper intake level (UL) for vitamin D at 50 mug (2000 IU)/d, defining this as "the highest level of daily nutrient intake that is likely to pose no risks of adverse health effects to almost all individuals in the general population." However, because sunshine can provide an adult with vitamin D in an amount equivalent to daily oral consumption of 250 mug (10,000 IU)/d, this is intuitively a safe dose. The incremental consumption of 1 mug (40 IU)/day of vitamin D(3) raises serum 25(OH)D by approximately 1 nM (0.4 ng/ml). Therefore, if sun-deprived adults are to maintain serum 25(OH)D concentrations >75 nM (30 ng/ml), they will require an intake of more than the UL for vitamin D. The mechanisms that limit vitamin D safety are the capacity of circulating vitamin D-binding protein and the ability to suppress 25(OH)D-1-alpha-hydroxylase. Vitamin D causes hypercalcemia when the "free" concentration of 1,25-dihydroxyvitamin D is inappropriately high. This displacement of 1,25(OH)(2)D becomes excessive as plasma 25(OH)D concentrations become higher than at least 600 nM (240 ng/ml). Plasma concentrations of unmetabolized vitamin D during the first days after an acute, large dose of vitamin D can reach the micromolar range and cause acute symptoms. The clinical trial evidence shows that a prolonged intake of 250 mug (10,000 IU)/d of vitamin D(3) is likely to pose no risk of adverse effects in almost all individuals in the general population; this meets the criteria for a tolerable upper intake level.

We report vitamin D toxicity in an infant following consecutive administration use of a large dose of vitamin D, causing symptomatic hypercalcemia, which was successfully managed with injectable calcitonin. However, the child developed bilateral medullary nephrocalcinosis which persisted 42 mon after the initial episode.

Recent interest in vitamin D has led to a substantial increase in the use of vitamin D supplements. Vitamin D intoxication may be a concern as hypervitaminosis D can result in irreversible calcification of soft tissues so that it is important to detect early markers of vitamin D intoxication. Our aim was to assess the simultaneous presence of biochemical markers of vitamin D toxicity (i.e. hypervitaminosis D, hypercalcemia) and determine the concentrations of 25-OH-vitamin D at which the risk of hypercalcemia, and thus toxicity, might begin.We evaluated retrospectively a 6-year period during which 25.567 samples were assessed for 25-OH-vitamin D status by UHPLC. Hypervitaminosis D was defined at serum 25-OH-vitamin D160 nmol/L. Serum and urine calcium, phosphorus and iPTH were also recorded, if available. Medical history revision was performed in subjects displaying simultaneously hypervitaminosis D and hypercalcemia.Overall, hypervitaminosis D was found in 475 samples (1.86%) of which 51 displayed hypercalcemia (11.1%). A total of 382 samples were identified as the first record of hypervitaminosis D and 39 presented hypercalcemia (10.2%), most of them at 25-OH-vitamin D levels between 161 and 375 nmol/L. Only in 15 subjects, hypercalcemia could be directly attributed to vitamin D and serum 25-OH-vitamin D ranged between 164 and 1139 nmol/l. In no case, serum calcium achieved concentrations considered as critical values (13 mg/dl).Hypercalcemia due to vitamin D represented4% of the total hypervitaminosis D detected and0.1% of the tests performed. However, a highly variable response was observed and most subjects presented hypercalcemia at serum concentrations of 25-OH-vitamin D 375 nmol/L.

In patients with tuberculosis, abnormal extrarenal production of 1,25-dihydroxyvitamin D3 by activated macrophages in granulomatous tissues may result in hypercalcaemia. More commonly reported in adults with active pulmonary tuberculosis, this complication may rarely occur in extrapulmonary tuberculosis, and children. The hypercalcaemia may be precipitated by usually recommended vitamin D and calcium supplementation in patients with tuberculosis. We report here an infant with tubercular meningitis who developed hypercalcaemia 12 days after starting routine vitamin D and calcium supplementation. This communication highlights the importance of close monitoring of calcium levels in patients with tuberculosis, especially if started on vitamin D and calcium replacement before anti-tubercular therapy.

Vitamin D toxicity also known as hypervitaminosis D was previously believed to be rare. But with an increase in vitamin D supplementation several cases have been reported in literature. Fat soluble vitamins like Vitamin D, due to their ability to accumulate in the body, have a higher potential for toxicity than water soluble vitamins. The main clinical consequence of vitamin D toxicity is hypercalcemia. In this report we describe an adult female patient who developed very high serum Vitamin D levels (746 ng/mL, RI: 20 to 50) as a result of medication error. Inspite of such high serum concentrations the patient was without any clinical symptoms and had normal serum calcium. We critically discuss the mechanism of toxicity and hypothesize the possible molecular/metabolic factors which might have been responsible for this nontoxic presentation. This case study highlights the fact that physicians need to consider the risk of medication errors while prescribing Vitamin D therapy. Clinical trials to study Vitamin D toxicity in humans is not possible ethically. Thus the evidence base regarding the safety profile of Vitamin D supplementation in humans has been build through case reports. This review of the paradoxical clinico-laboratory manifestation of hypervitaminosis D could possibly contribute to existing literature.

Vitamin D toxicity from unactivated vitamin D (calciferol) therapy is currently a rare cause of hypercalcaemia. However, the frequency of this event may increase as high-dose unactivated vitamin D preparations become available. Prolonged vitamin D toxicity can cause reversible hypercalcaemia and partially reversible renal impairment. Parathyroid hormone may not be suppressed with unactivated vitamin D toxicity, especially if renal disease coexists.

Vitamin D deficiency is widely prevalent across the globe. This has lead to widespread use of vitamin D supplements in populations. We present our experience of vitamin D toxicity in a subject resulting in hypercalcemia and CHB (Complete Heart Block). A 70-year-old female, known hypertensive for thirty five years and diabetic for seven years underwent total knee replacement (TKR) for osteoarthritis left knee in December 2010. For perioperative glycemic control, multiple subcutaneous injections of insulin were advised. Patient later presented with poor glycemic control, decreased appetite and constipation for last 1 month with history of episodes of transient loss of consciousness for 15 days and recurrent vomiting. Biochemical work-up showed hypercalcemia (Serum calcium 12.4 mg/dL). Sr. albumin, ALP, Sr. phosphorus and PTH levels were normal, thus suggesting PTH independent hypercalcemia. Strong suspicion led us to check vitamin D levels in dilution which were 2016 ng/mL, thus confirming vitamin D toxicity. Retrospective analysis of treatment history revealed patient receiving 4 injections of Architol (6 Lac units im) prior to presentation. Work-up for malignancy was negative, brain imaging and EEG were normal. Holter was suggestive of intermittent CHB. Patient was given hydration, injection calcitonin 100 I.U. subcutaneously, injection pamidronate 60 mg infusion, with serum calcium levels normalizing, with relief in constipation, vomiting and behavioral improvement. However, persistence of rhythm disturbances led to permanent pacemaker placement. The present case highlights the dangers of indiscriminate vitamin D usage, exposing patients to potentially life threatening complications.

Case series summary This case series describes two young sibling cats and an additional unrelated cat, from two separate households, that developed hypercalcaemia associated with hypervitaminosis D. Excessive vitamin D concentrations were identified in a natural complementary tinned kitten food that was fed to all three cats as part of their diet. In one of the cases, there was clinical evidence of soft tissue mineralisation. The hypercalcaemia and soft tissue mineralisation resolved following withdrawal of the affected food and medical management of the hypercalcaemia. Relevance and novel information This case series demonstrates the importance of obtaining a thorough dietary history in patients presenting with hypercalcaemia and the measurement of vitamin D metabolites when investigating such cases. Complementary foods may have the potential to induce nutritional toxicity even when fed with complete, nutritionally balanced diets.