The first aim was to examine the effects of genes, stage of development, and environment on rickets, and to relate these influences to clinical and public-health concerns. Literature searches of PubMed were done with the keywords “rickets” or “vitamin D” alone and then with “genes, or genetics”, specified ages, “sun”, “treatment”, “prevention”, and specific countries, with subsearches as necessary (eg, “weaning + calcium + phytate”). The choice of papers to quote was related to their
SeminarRickets
Section snippets
What is rickets?
Endochondral ossification is the process by which cartilage is transformed into bone. The cartilage matrix produced by hypertrophic chondrocytes is calcified before being reabsorbed and replaced with woven bone, which in turn is removed and replaced with mature lamellar bone. During these processes, there is extensive deposition of new unmineralised bone tissue, known as osteoid. Rickets is the failure to mineralise this newly formed osteoid. Bones grow longer during childhood, and they must
Genetics and molecular biology
There is little evidence of any specific genetic predisposition to nutritional rickets. Polymorphisms of the vitamin D receptor (VDR) have been studied extensively in adults, but less so in children. Fischer and colleagues reported an increased frequency of the VDR FF genotype in Nigerian children with rickets.42 Paradoxically, the FF genotype is thought to encode a “better functioning” receptor. However, Nigerian children are at risk of calcium-deficiency rickets rather than that caused by
Vitamin D metabolism
Failure to convert calcidiol to calcitriol causes rickets. Such failure is caused by a defect in the gene encoding vitamin D 1α-hydroxylase, which is expressed in the mitochondria of proximal tubular and, to a lesser extent, collecting-duct cells of the kidney. This enzyme is regulated by calcium, phosphate, parathyroid hormone, calcitonin, calcitriol, and intracellular vitamin-D-binding protein 1.45 The clinical picture with this gene defect is one of severe rickets with hypocalcaemia commonly
Phosphate
Studies of three different disorders of phosphate metabolism have advanced the concept of a circulating factor (or factors) that might have a role in regulating phosphate homoeostasis.38 The commonest inherited form of rickets is X-linked hypophosphataemic rickets, which is caused by mutations in PHEX (Phosphate-regulating gene with Homologies to Endopeptidases, on the X chromosome). PHEX is predominantly expressed in osteoblasts. Individuals with this disorder have higher than normal urinary
Stages of development
Three components of development are relevant to rickets: growth, body composition, and biological events. Figure 3 explains why simple rickets is most common in infancy and at puberty and emphasises the importance of later fetal life and infancy for events affecting bones and teeth subsequently.51, 52, 53, 54, 55, 56
Growth is rapid in late fetal life (slowing somewhat during the last 2–3 weeks) and early infancy. The rate falls in the toddler years then rises for the prepubertal growth spurt
Sunlight
The contribution of the sun to vitamin D synthesis depends on latitude, season, exposure to direct sunlight, and skin colour (panel 6). Ultraviolet B radiation of wavelength 290–310 nm leads to the conversion (photolysis) of 7-dihydrocholesterol in the skin to precholecalciferol, which then undergoes thermally induced rearrangement of its double bonds to form cholecalciferol (vitamin D3).
There may be wider evolutionary concepts. The clinical gradation of skin colour could be related to levels
Prevention
Methods of prevention are the same as for any other nutrient deficiency, plus the need to promote exposure to sunlight. The parts played by the methods listed in panel 7 will vary according to country depending on the physical environment, cultural factors, diet (including national policies on food fortification), and socioeconomic factors (access to health services including policies for and provision of supplements).
Search strategy
References (138)
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Lancet
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The effect of vitamin D on linear growth in infancy
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(1936) Why is rickets resurgent in the USA?
Lancet
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(2001) Does ‘imprinting’ with low prenatal vitamin D contribute to the risk of various adult disorders?
Med Hypotheses
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Neonatal factors predicting childhood height in preterm infants: evidence for a persisting effect of early metabolic bone disease?
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High turnover osteopenia in preterm babies
Bone
(1994)
Risk factors for vitamin D deficiency in breast-fed newborns and their mothers
Nutrition
Perinatal metabolism of vitamin D
Am J Clin Nutr
Bone mineral content is not reduced despite low vitamin D status in breast milk-fed infants versus cow's milk based formula-fed infants
J Pediatr
Nutritional rickets in African American breast-fed infants
J Pediatr
Effect of iron on serum 25-hydroxy vitamin D and 24,25-dihydroxy vitamin D concentrations
Am J Clin Nutr
Serum 25-hydroxyvitamin D status of adolescents and adults in two seasonal subpopulations from NHANES 111
Bone
Case control study of the role of nutritional rickets in the risk of developing pneumonia in Ethiopian children
Lancet
Rickets in children of rural origin in South Africa: is low dietary calcium a factor?
J Pediatr
Healing of rickets after calcium supplementation
Lancet
An experimental investigation of rickets
Lancet
Die Behandlung der Rachitis durch Ultraviolet-bestrahlung
Z Orthop Chir
Vitamin D: metabolism and mechanism of action
World Rev Nutr Diet
Infantile hypercalcaemia
Cod-liver oil, vitamin D and the fight against rickets
Can Med Assoc J
Characteristics of children with florid vitamin D deficient rickets in the Auckland region in 1998
N Z Med J
Vitamin D deficiency in UK Asian families: activating a new concern
Arch Dis Child
Vitamin D deficiency in mothers of infants with rickets
Med J Aust
Vitamin D deficiency rickets in developing countries
Ann Trop Paediatr
Vitamin D and the pathogenesis of rickets and osteomalacia
Is craniotabes a pathognomonic sign of rickets in 3-month-old infants?
S Afr Med J
Nervous system in rhachitis. Cited by DeJong AR, Callahan CA, Weiss J. Pseudotumor cerebri and nutritional rickets
Eur J Pediatr
Benign intracranial hypertension in vitamin D deficiency rickets associated with malnutrition
J Trop Pediatr
The usefulness of clinical features to identify active rickets
Ann Trop Paediatr
Brown tumour as a complication of secondary hyperparathyroidism in severe long-lasting vitamin D deficiency rickets
Eur J Pediatr
Vitamin deficiency in a toddler reluctant to use her arm
Eur J Emerg Med
Radiographic scoring method for the assessment of the severity of nutritional rickets
J Trop Pediatr
Prematurity and rickets
Pediatrics
Cause and clinical characteristics of rib fractures in infants
Pediatrics
Cardiac functions in children with vitamin D deficiency rickets
Pediatr Cardiol
Rickets related myelofibrosis
Eur J Pediatr
An ecologic study of dietary and solar ultraviolet-B links to breast carcinoma mortality rates
Cancer
Regional variation in multiple sclerosis prevalence in Australia and its association with ambient ultraviolet radiation
Neuroepidemiology
Intrauterine vitamin D nutrition and postnatal growth in Asian infants
BMJ
Clinical biochemistry and the sick child, 2nd edn
How much vitamin D supplementation do adults require to ensure a serum 25(OH)D optimal for suppression of PTH?
J Bone Miner Res
Issues of standardization and assay-specific clinical decision limits for the measurement of 25-hydroxyvitamin D
Am Soc Clin Nutr
Serum osteocalcin has limited usefulness as a diagnostic marker for rickets
Eur J Pediatr
Rickets as an unusual initial presentation of abetalipoproteinemia and hypobetalipoproteinemia
J Pediatr Endocrinol
The role of 1,25-dihydroxyvitamin D in the mechanism of acquired vitamin D deficiency
Clin Endocrinol
Hepatic osteodystrophy in chronic cholestasis: evidence for a multifactorial etiology
Pediatr Trans
Cited by (319)
Nutritional rickets masquerading as spinal muscular atrophy type III
2023, Neuromuscular DisordersProbable micronutrient deficiency diseases in a rural community. The nonadults of Mary's Nativity church, 16th century, Trentino Alto-Adige, Italy
2023, Journal of Archaeological Science: ReportsCitation Excerpt :Among micronutrient deficiency, rickets and scurvy have received much attention from scholars. They are caused, respectively, by the lack of vitamin D and C (Carpenter, 1988; Wharton and Bishop, 2003). The typical bone evidence of these pathologies can be present at the same time on the same subject, in what is defined as a co-occurrence disease, which occurs, as reported by Buikstra (2019) “where multiple (patological) conditions occur simultaneously” (see also Schattmann et al., 2016; Brickley et al., 2018; Brickley et al., 2020).
Vitamin D in dentoalveolar and oral health
2023, Feldman and Pike's Vitamin D: Volume One: Biochemistry, Physiology and DiagnosticsVitamin D deficiency and nutritional rickets in infants and children
2023, Feldman and Pike's Vitamin D: Volume Two: Disease and TherapeuticsTime out: Should vitamin D dosing be based on patient's body mass index (BMI): A prospective controlled study
2021, Journal of Nutritional Science