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The Journal of Clinical Endocrinology... Feb 2016Vitamin D and calcium deficiencies are common worldwide, causing nutritional rickets and osteomalacia, which have a major impact on health, growth, and development of... (Review)
Review
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.
Topics: Calcium; Child; Child, Preschool; Consensus; Health Policy; Humans; Infant; Mothers; Osteomalacia; Recommended Dietary Allowances; Rickets; Risk Factors; Vitamin D; Vitamin D Deficiency; Vitamins
PubMed: 26745253
DOI: 10.1210/jc.2015-2175 -
Hormone Research in Paediatrics 2022Rickets was a major public health problem dating from Roman times, and medical descriptions of rickets date from the 17th century. Sniadecki first advocated treatment by... (Review)
Review
Rickets was a major public health problem dating from Roman times, and medical descriptions of rickets date from the 17th century. Sniadecki first advocated treatment by exposure to sunshine in 1822; contemporaneously, several British physicians advocated use of cod liver oil. Both approaches were successful. Work in 1924 showed that exposure to UV light endowed fats and other foods with antirachitic properties. Vitamins D2 and D3, the antirachitic agent in cod liver oil, were, respectively, produced by UV radiation of ergosterol and 7-dehydrocholesterol. Calcitriol (1,25[OH]2D3) was identified as the biologically active form of vitamin D in the early 1970s. The vitamin D 25-hydroxylase, 24-hydroxylase, and 1α-hydroxylase were cloned in the 1990s and their genetic defects were soon delineated. The vitamin D receptor was also cloned and its mutations identified in vitamin D-resistant rickets. Work with parathyroid hormone (PTH) began much later, as the parathyroids were not identified until the late 19th century. In 1925, James B. Collip (of insulin fame) identified PTH by its ability to correct tetany in parathyroidectomized dogs, but only in the 1970s was it clear that only a small fragment of PTH conveyed its activity. Congenital hypoparathyroidism with immune defects was described in 1968, eventually linked to microdeletions in chromosome 22q11.2. X-linked hypophosphatemic rickets was reported in 1957, and genetic linkage analysis identified the causative PHEX gene in 1997. Autosomal dominant hypophosphatemic rickets similarly led to the discovery of FGF23, a phosphate-wasting humoral factor made in bone, in 2000, revolutionizing our understanding of phosphorus metabolism.
Topics: Animals; Dogs; Humans; Cod Liver Oil; Familial Hypophosphatemic Rickets; Parathyroid Hormone; Rickets; Vitamin D; Vitamins
PubMed: 36446330
DOI: 10.1159/000527011 -
Nature Reviews. Endocrinology Feb 2022Vitamin D supplementation can prevent and cure nutritional rickets in infants and children. Preclinical and observational data suggest that the vitamin D endocrine... (Review)
Review
Vitamin D supplementation can prevent and cure nutritional rickets in infants and children. Preclinical and observational data suggest that the vitamin D endocrine system has a wide spectrum of skeletal and extra-skeletal activities. There is consensus that severe vitamin D deficiency (serum 25-hydroxyvitamin D (25OHD) concentration <30 nmol/l) should be corrected, whereas most guidelines recommend serum 25OHD concentrations of >50 nmol/l for optimal bone health in older adults. However, the causal link between vitamin D and many extra-skeletal outcomes remains unclear. The VITAL, ViDA and D2d randomized clinical trials (combined number of participants >30,000) indicated that vitamin D supplementation of vitamin D-replete adults (baseline serum 25OHD >50 nmol/l) does not prevent cancer, cardiovascular events, falls or progression to type 2 diabetes mellitus. Post hoc analysis has suggested some extra-skeletal benefits for individuals with vitamin D deficiency. Over 60 Mendelian randomization studies, designed to minimize bias from confounding, have evaluated the consequences of lifelong genetically lowered serum 25OHD concentrations on various outcomes and most studies have found null effects. Four Mendelian randomization studies found an increased risk of multiple sclerosis in individuals with genetically lowered serum 25OHD concentrations. In conclusion, supplementation of vitamin D-replete individuals does not provide demonstrable health benefits. This conclusion does not contradict older guidelines that severe vitamin D deficiency should be prevented or corrected.
Topics: Aged; Child; Diabetes Mellitus, Type 2; Dietary Supplements; Humans; Infant; Rickets; Vitamin D; Vitamin D Deficiency
PubMed: 34815552
DOI: 10.1038/s41574-021-00593-z -
Endocrine Reviews Aug 2019The 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... (Review)
Review
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.
Topics: Animals; Bone and Bones; Calcium; Female; Humans; Male; Osteomalacia; Rickets; Signal Transduction; Vitamin D; Vitamin D Deficiency
PubMed: 30321335
DOI: 10.1210/er.2018-00126 -
Indian Pediatrics Feb 2022The emerging literature on prevalence of vitamin D deficiency in India, prevention and treatment strategies of rickets, and extra-skeletal benefits of vitamin D suggest...
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.
Topics: Adolescent; Child; Cholecalciferol; Dietary Supplements; Humans; Pediatrics; Rickets; Vitamin D; Vitamin D Deficiency; Vitamins
PubMed: 34969941
DOI: No ID Found -
Annals of Nutrition & Metabolism 2020Vitamin D is necessary for the active (transcellular) absorption of calcium and for skeletal health. Inadequate vitamin D in infants leads to increased risks of poor... (Review)
Review
Vitamin D is necessary for the active (transcellular) absorption of calcium and for skeletal health. Inadequate vitamin D in infants leads to increased risks of poor bone mineralization and ultimately rickets. Rickets is uncommon in full-term infants with a much higher risk in very premature infants. However, the primary cause of rickets in premature infants is a deficiency of calcium and phosphorus, not vitamin D. Available research, as well as most guidelines, recommend an intake of 400 IU daily of vitamin D as adequate for bone health in preterm and full-term infants. Higher doses have not been consistently shown to have specific clinical benefits for healthy infants. There are no strong data to support either routine testing of serum 25-hydroxyvitamin D or targeting high serum 25-hydroxyvitamin D levels (e.g., 30 ng/mL) in healthy preterm or full-term infants. Vitamin D is commonly provided to infants via drops for breastfed babies or via infant formula, although alternative dosing approaches exist for breastfed infants, which some families may prefer. These include the use of drops placed on the mother's breast, dissolvable doses, and high maternal doses (approximately 6,400 IU daily). Infant formula contains vitamin D, and most infants will reach an intake from formula of about 400 IU daily within the first 2 months of life if they are consuming routine cow milk-based formula. Although vitamin D toxicity is very uncommon, caution should be used to avoid extremely concentrated high doses found in some commercially available drops. Infants with liver or kidney disease may need special attention to vitamin D intake and status. Further research is needed to define the role of vitamin D in non-bone health outcomes of infants and to identify methods to enhance compliance with current recommendations for vitamin D intake in infants.
Topics: Female; Humans; Infant Nutritional Physiological Phenomena; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Male; Rickets; Term Birth; Vitamin D; Vitamin D Deficiency
PubMed: 33232955
DOI: 10.1159/000508421 -
The American Journal of Clinical... Apr 2008Vitamin D deficiency is now recognized as a pandemic. The major cause of vitamin D deficiency is the lack of appreciation that sun exposure in moderation is the major... (Review)
Review
Vitamin D deficiency is now recognized as a pandemic. The major cause of vitamin D deficiency is the lack of appreciation that sun exposure in moderation is the major source of vitamin D for most humans. Very few foods naturally contain vitamin D, and foods that are fortified with vitamin D are often inadequate to satisfy either a child's or an adult's vitamin D requirement. Vitamin D deficiency causes rickets in children and will precipitate and exacerbate osteopenia, osteoporosis, and fractures in adults. Vitamin D deficiency has been associated with increased risk of common cancers, autoimmune diseases, hypertension, and infectious diseases. A circulating level of 25-hydroxyvitamin D of >75 nmol/L, or 30 ng/mL, is required to maximize vitamin D's beneficial effects for health. In the absence of adequate sun exposure, at least 800-1000 IU vitamin D3/d may be needed to achieve this in children and adults. Vitamin D2 may be equally effective for maintaining circulating concentrations of 25-hydroxyvitamin D when given in physiologic concentrations.
Topics: Autoimmune Diseases; Bone Density; Bone Density Conservation Agents; Bone and Bones; Cardiovascular Diseases; Food, Fortified; Global Health; Humans; Neoplasms; Nutritional Requirements; Rickets; Sunlight; Vitamin D; Vitamin D Deficiency
PubMed: 18400738
DOI: 10.1093/ajcn/87.4.1080S -
The Journal of Clinical Endocrinology... Dec 2022Hypophosphatemic rickets typically presents in infancy or early childhood with skeletal deformities and growth plate abnormalities. The most common causes are genetic...
Hypophosphatemic rickets typically presents in infancy or early childhood with skeletal deformities and growth plate abnormalities. The most common causes are genetic (such as X-linked hypophosphatemia), and these typically will result in lifelong hypophosphatemia and osteomalacia. Knowledge of phosphate metabolism, including the effects of fibroblast growth factor 23 (FGF23) (an osteocyte produced hormone that downregulates renal phosphate reabsorption and 1,25-dihydroxyvitamin-D (1,25(OH)2D) production), is critical to determining the underlying genetic or acquired causes of hypophosphatemia and to facilitate appropriate treatment. Serum phosphorus should be measured in any child or adult with musculoskeletal complaints suggesting rickets or osteomalacia. Clinical evaluation incudes thorough history, physical examination, laboratory investigations, genetic analysis (especially in the absence of a guiding family history), and imaging to establish etiology and to monitor severity and treatment course. The treatment depends on the underlying cause, but often includes active forms of vitamin D combined with phosphate salts, or anti-FGF23 antibody treatment (burosumab) for X-linked hypophosphatemia. The purpose of this article is to explore the approach to evaluating hypophosphatemic rickets and its treatment options.
Topics: Adult; Child; Child, Preschool; Humans; Familial Hypophosphatemic Rickets; Osteomalacia; Fibroblast Growth Factors; Rickets, Hypophosphatemic; Hypophosphatemia; Phosphates
PubMed: 35981346
DOI: 10.1210/clinem/dgac488 -
Pediatric Nephrology (Berlin, Germany) Sep 2022Rickets is a disease of the growing child arising from alterations in calcium and phosphate homeostasis resulting in impaired apoptosis of hypertrophic chondrocytes in... (Review)
Review
Rickets is a disease of the growing child arising from alterations in calcium and phosphate homeostasis resulting in impaired apoptosis of hypertrophic chondrocytes in the growth plate. Its symptoms depend on the patients' age, duration of disease, and underlying disorder. Common features include thickened wrists and ankles due to widened metaphyses, growth failure, bone pain, muscle weakness, waddling gait, and leg bowing. Affected infants often show delayed closure of the fontanelles, frontal bossing, and craniotabes. The diagnosis of rickets is based on the presence of these typical clinical symptoms and radiological findings on X-rays of the wrist or knee, showing metaphyseal fraying and widening of growth plates, in conjunction with elevated serum levels of alkaline phosphatase. Nutritional rickets due to vitamin D deficiency and/or dietary calcium deficiency is the most common cause of rickets. Currently, more than 20 acquired or hereditary causes of rickets are known. The latter are due to mutations in genes involved in vitamin D metabolism or action, renal phosphate reabsorption, or synthesis, or degradation of the phosphaturic hormone fibroblast growth factor 23 (FGF23). There is a substantial overlap in the clinical features between the various entities, requiring a thorough workup using biochemical analyses and, if necessary, genetic tests. Part I of this review focuses on the etiology, pathophysiology and clinical findings of rickets followed by the presentation of a diagnostic approach for correct diagnosis. Part II focuses on the management of rickets, including new therapeutic approaches based on recent clinical practice guidelines.
Topics: Alkaline Phosphatase; Child; Fibroblast Growth Factors; Humans; Infant; Phosphates; Rickets; Vitamin D Deficiency
PubMed: 34910242
DOI: 10.1007/s00467-021-05328-w -
The Indian Journal of Medical Research Oct 2020Defective mineralization of the growth plate and preformed osteoid result in rickets and osteomalacia, respectively. The leading cause of rickets worldwide is solar... (Review)
Review
Defective mineralization of the growth plate and preformed osteoid result in rickets and osteomalacia, respectively. The leading cause of rickets worldwide is solar vitamin D deficiency and/or dietary calcium deficiency collectively termed as nutritional rickets. Vitamin D deficiency predominates in high-latitude countries in at-risk groups (dark skin, reduced sun exposure, infants and pregnant and lactating women) but is emerging in some tropical countries due to sun avoidance behaviour. Calcium deficiency predominates in tropical countries, especially in the malnourished population. Nutritional rickets can have devastating health consequences beyond bony deformities (swollen wrist and ankle joints, rachitic rosary, soft skull, stunting and bowing) and include life-threatening hypocalcaemic complications of seizures and, in infancy, heart failure due to dilated cardiomyopathy. In children, diagnosis of rickets (always associated with osteomalacia) is confirmed on radiographs (cupping and flaring of metaphyses) and should be suspected in high risk individuals with the above clinical manifestations in the presence of abnormal blood biochemistry (high alkaline phosphatase and parathyroid hormone, low 25-hydroxyvitamin D and calcium and/or low phosphate). In adults or adolescents with closed growth plates, osteomalacia presents with non-specific symptoms (fatigue, malaise and muscle weakness) and abnormal blood biochemistry, but only in extreme cases, it is associated with radiographic findings of Looser's zone fractures. Bone biopsies could confirm osteomalacia at earlier disease stages, for definitive diagnosis. Treatment includes high-dose cholecalciferol or ergocalciferol daily for a minimum of 12 wk or stoss therapy in exceptional circumstances, each followed by lifelong maintenance supplementation. In addition, adequate calcium intake through diet or supplementation should be ensured. Preventative approaches should be tailored to the population needs and incorporate multiple strategies including targeted vitamin D supplementation of at-risk groups and food fortification with vitamin D and/or calcium. Economically, food fortification is certainly the most cost-effective way forward.
Topics: Adolescent; Calcium; Child; Female; Humans; Infant; Lactation; Osteomalacia; Pregnancy; Rickets; Vitamin D; Vitamin D Deficiency; Vitamins
PubMed: 33380700
DOI: 10.4103/ijmr.IJMR_1961_19