Vitamin D Deficiency Rickets in a Sunny Country: Pathogenesis, Clinical Picture and Management
1987; King Faisal Specialist Hospital and Research Centre; Volume: 7; Issue: 2 Linguagem: Inglês
10.5144/0256-4947.1987.119
ISSN0975-4466
Autores Tópico(s)Climate Change and Health Impacts
ResumoOriginal ArticlesVitamin D Deficiency Rickets in a Sunny Country: Pathogenesis, Clinical Picture and Management Abdelwahab T. H. ElidrissyFRCP(E), DCH Abdelwahab T. H. Elidrissy Associate Professor and Consultant Pediatrician, College of Medicine and, King Khalid University Hospital, P. O. Box 2925, Riyadh 11461, Saudi Arabia Search for more papers by this author Published Online:1 Apr 1987https://doi.org/10.5144/0256-4947.1987.119SectionsPDF ToolsAdd to favoritesDownload citationTrack citations ShareShare onFacebookTwitterLinked InRedditEmail AboutABSTRACTABSTRACTVitamin D deficiency rickets occurs in sunny countries, mainly due to man-made environmental factors associated with avoidance of sunshine. This situation can be prevented by more health education regarding exposure to sunshine. Designs of houses in urban areas need to be changed to allow for such exposure while still maintaining privacy. Fortification of foods with vitamin D is not without hazards and need not be advocated, but the risk groups can be given vitamin D supplementation in physiological doses. The tragic effects of vitamin D intoxication must be always borne in mind when prescribed as prophylaxis in massive doses. Finally, vitamin D deficiency diseases can be eradicated by more exposure to the sun.INTRODUCTIONRickets is a disease of growing bones characterized by failure of calcification of cartilage and osteoid tissue in bone, leading to their accumulation in an abnormal form. It is classified as vitamin D deficiency, or vitamin D resistant rickets. Vitamin D deficiency is caused either by lack of sunshine or insufficient vitamin D content of the diet. Deficiency rickets used to be a disease of temperate countries with its prevalence stated to be equivalent to a map of lack of sunshine.1Fortification of infant foods with vitamin D led to eradication of the disease in temperate countries,2 but it has emerged among Asian immigrants due to low dietary vitamin D and lack of sunshine.3,4 Recently, it was shown that there is no genetically determined characteristic causing vitamin D deficiency among immigrant Asians and it is the change of environment that plays the major role.5 The effect of skin pigmentation is still controversial.In sunny countries rickets is also seen in such a magnitude as to be considered a community health problem.6–14 This communication reviews the factors associated with development of rickets in a country where there is abundance of sunshine.DISCUSSIONVitamin D Metabolism and FunctionsVitamin D is a sterol which is naturally present in two forms: (1) cholecalciferol, or vitamin D3, which is obtained through the action of ultraviolet rays on provitamin 7-dehydrocholesterol in the skin, and (2) ergocalciferol, or vitamin D2, which is of plant origin. The natural and main source of vitamin D, even in temperate countries, is still through exposure to sunshine.15–17Vitamin D from either source is hydroxylated first in the liver to form 25-hydroxyvitamin D (25- OHD)18 then in the kidneys to form the active metabolite 1,25-dihydroxyvitamin D [1,25-(OH)2D].19 This hormone regulates calcium and phosphorous homeostasis by promoting absorption of calcium and phosphate in the intestine and enhancing renal tubular reabsorption of calcium. In bone, both 1,25(OH)2D and parathormone are required in physiologic concentrations to mobilize calcium (Figure 1). Measurement of the level of 25-OHD in the blood is used as an index of vitamin D status and stores, whereas the level of l,25(OH)2D is used as an index of its activity.Figure 1. Metabolic pathways of vitamin D.Download FigureEffects of Vitamin D DeficiencyThe initial outcome of vitamin D deficiency is hypocalcemia, followed by hypophosphatemia and a rise of alkaline phosphatase. These findings are termed biochemical rickets or osteomalacia. The hypophosphatemia, although an invariable finding in vitamin D deficiency rickets, might not be as striking as is the hypocalcemia in the early stage of the disease.20 The hypocalcemia stimulates the parathormone which, in turn, leads to resorption of calcium from bone in an attempt to maintain normal serum calcium, thereby leaving a demineralized bone.21In growing bones the bone matrix continues to be produced, causing impairment of the epiphyseal ends of bones. This is manifested clinically in areas of fast bone growth (e.g., wrist, costochondral junction); however, in the weight-bearing long bones, decalcification makes them bend.Pathogenesis of Rickets in a Sunny AreaThe level of ultraviolet rays available in the atmosphere in Riyadh is consistent with what is expected at such an altitude,22 and those rays that reach the usually exposed human skin are sufficient to maintain adequate circulating levels of 25- OHD.23 Then why do we see rickets in such a place? In trying to answer this question, I will first discuss the interrelations of vitamin D status between mother and infant.Maternal Vitamin D Deficiency Causing Rickets in InfantsIn Riyadh, rickets commonly occurs in the first year of life, with a mean age of ten months.6, 24 Although cases of congenital rickets have been reported,25,26 the youngest infant seen with clinical rickets in our series was two months old, and this presented with hypocalcemic convulsions associated with minimal bony changes.24 The mothers of rachitic infants were found to be vitamin-D deficient,27 and paired maternal and cord blood vitamin D status proved to be low.28,29 In spite of this low 25-OHD, calcium levels in cord blood were maintained within normal limits and were even higher than the corresponding maternal levels.30,31 These findings conform to the active transplacental transport of calcium,32,33 which could be explained by the high levels of l,25(OH)2D during pregnancy,34,35 especially since the placenta36 and the fetus37 can act as additional sites for the metabolism of l,25(OH)2D. We have demonstrated normal or high levels of l,25(OH)2D in pregnancy in spite of the low levels of 25-OHD,38 and lack of correlation between the two metabolites was shown.39 In our series, even in extremely low 25-OHD levels among pregnant women, no infant was reported as born with clinical evidence of rickets31 but there was a high incidence of neonatal hypocalcemia.30 High parity was not found to be a factor in the low maternal vitamin D status.30,39 The active transplacental calcium transfer in spite of poor vitamin D status of the mother was found to maintain adequate fetal bone mineralization and prevent congenital rickets except in states of severe maternal osteomalacia.40The maternal vitamin-D-deficiency state during pregnancy leads to delivery of infants with poor vitamin D stores. After birth these infants are unable to maintain normal calcium levels due to the loss of the active transplacental calcium pump and lack of vitamin D reserves. This manifests as neonatal hypocalcemia in some.30,41 The others might present later, depending on vitamin D content of the milk and environmental exposure to the sun.42 If these infants are breast-fed and not exposed to sunshine, development of rickets becomes inevitable, particularly in light of the mothers’ belief that the sun will hurt their infants.42 Infants born with adequate vitamin D stores do not need vitamin D supplements to breast-feeding for the first six months of life.43 The vitamin D content of breast milk is discussed later.The evidence available supports the hypothesis that maternal vitamin D deficiency contributes to rickets in infants6 and this is demonstrated in Figure 2. Infantile rickets in Libya was attributed to similar low maternal and cord blood 25-OHD levels.44 As the mother and infant are affected by vitamin D deficiency, we assume that environmental factors add up to form a sort of umbrella which deprives them of sunshine.Figure 2. Flow chart of the development of rickets.Download FigureEnvironmental Factors Leading to Vitamin D DeficiencyHousing. Most of the rachitic infants were living in either flats or traditional mud houses.6,24 The traditional mud house is high walled with small, high windows. Neither of these types of dwellings offer direct access to sunshine, in contrast to rural houses that have courtyards where mothers and their children can have privacy and still be exposed to sunlight. The lowest levels of vitamin D among pregnant mothers were found in those women who lived in traditional houses and flats.29Location. The location of dwellings may also contribute to vitamin D deficiency. This is supported by the finding that almost all of the rachitic infants come from crowded parts of the city.27 In these areas, the mothers together with their infants, remain indoors with no chance of being exposed to sunshine. Historically, this simulates what used to be seen in Europe following the industrial revolution when rickets was endemic in the slums of big cities.2 In contrast to the European cities, there is no problem with lack of ultraviolet rays in Riyadh,21,22 but there is lack of exposure to the rays.The urbanization umbrella. Sunlight is abundant in Riyadh but an environmental ‘umbrella’ is formed, depriving the infants and their mothers of access to sunshine.45 Urbanization forms the main centerpost on which this umbrella is pivoted, as illustrated in Figure 3. Urbanization is associated with living in flats that are devoid of sunshine. Ultraviolet light does not penetrate glass. Rickets is seen because of man-made factors preventing access to the available ultraviolet rays needed for synthesis of vitamin D. The statement by Park, before the discovery of vitamin D, that rickets is a disease of artificial ways of living and never associated with natural life46 still holds true in sunny countries whose inhabitants used to be immune to the disease.Figure 3. The urbanization umbrella that reduces exposure to sunlight.Download FigureCustomsWomen's clothing. Since purdah by some of the immigrants in Europe was considered as a major factor in the prevalence of rickets and osteomalacia, we studied the pattern of dressing and its relation to the occurrence of rickets. The traditional attire of females in Riyadh did not contribute to vitamin D deficiency as it was found that 25-OHD levels of female students were similar to those of male students.47 Also, school girls aged 6-19 years did not show a drop in levels of 25-OHD coinciding with their change at puberty to traditional dress.48 In rural areas where women wear similar traditional dress, rickets is not a problem.6,49 This could be explained by the fact that houses have courtyards where exposure to sunshine can be achieved while carrying out home duties. From the available evidence, it can be stated that the women's style of dress perse is not a reason for their vitamin D deficiency.Wrapping infants. Covering of infants for about four months after birth is common, caused by the belief that sunlight will hurt newborns.42 We reported this custom as a factor in causation of rickets in a previous communication,6 but subsequent evidence does not support our earlier conclusion.Breast-feeding and Vitamin D ContentA high percentage of infants in our series were breast-fed, and the few who were bottle-fed were on brands of milk which were not fortified with vitamin D. The majority of rachitic infants had normal protein calorie nutritional status, indicating that it was not part of generalized malnutrition.24 This proves that breast-feeding can maintain an adequate nutritional status for the first six to nine months of life,50 but it does not supply infants with enough vitamin D to meet the needs of bone growth.51,52 It has been proven beyond doubt that there is no water-soluble vitamin D sulphate in breast milk.52,53Recent reports showed normal vitamin D status and bone mineralization up to the age of one year in breast-fed infants fed by vitamin-D-sufficient mothers,54,55 and conclude that although the concentration of vitamin D in human milk appears to be low, there is enough of it to prevent bone demineralization. A further report has demonstrated low vitamin D status in unsupplemented breast-fed infants,56 but this does not necessarily mean decalcification. From the available data, it can be stated that it is the maternal vitamin D status during pregnancy, and not vitamin D content of breast milk, that determines bone mineralization of the infant in the first six months of life.EpidemiologyRickets is seen in Riyadh at a mean age of ten months. The usual presentation is by symptoms not directly related to the disease, and the diagnosis can be missed. Accordingly, the true incidence is difficult to elicit.6 The diagnosed cases formed 0.7% of the admissions to Riyadh Children's Hospital.57 Since the majority of the rachitic infants have normal protein calorie nutritional status,24 it is difficult to elicit the physical signs of rickets, such as swollen wrists and costochondral beading. The true incidence of rickets still awaits an epidemiological survey.Clinical PictureClassical rickets in toddlers and older children presents with typical bow legs and waddling gait, but in infants it presents with respiratory and gastrointestinal symptoms and signs of rickets may pass unnoticed. Craniotabes is detected in the occiput only in early life, and during the first six months of life hypocalcemic convulsions can occur. At this stage, it is subclinical; radiology of the bones of the forearm will reveal either minor changes or no changes at all. The hypocalcemic convulsions may be precipitated by fever, and after the age of six months may be passed as simple febrile convulsions. In the second year of life, delayed walking and eruption of teeth usually warrant seeking medical advice. It is only when the child is walking that bowing of the legs and waddling gait become obvious causes for concern. Excessive sweating is noted in some children.The signs commonly encountered are swollen wrist, rachitic rosary, bossing of the forehead, delayed dentition, hypotonia and craniotabes.DiagnosisDiagnosis of rickets in infants depends mainly on suspecting the condition and looking for its signs among children presenting with common pediatric ailments, including chest infection and gastroenteritis. The signs to be looked for are widening of the distal end of the forearm, bossing of the forehead and rachitic rosary at the costochondral junctions, though these are better felt than seen. Confirmation of the diagnosis is established by radiological evidence of rickets at the wrist. In early stages of the disease diagnosis can be made by the presence of very high alkaline phosphatase, with or without hypocalcemia in the absence of other causes of high alkaline phosphatase. In a toddler, diagnosis of rickets is easy since the child presents with bowed legs and waddling gait, but, of course, not all bowed legs are due to rickets.PreventionIn sunny countries, exposure to the sun is the most natural and best method of preventing rickets. Houses should be designed in ways that allow exposure to the sun, especially for mothers, while still maintaining privacy. The period of exposure does not necessarily have to be long. A weekend in the desert is a Saudi custom which, if carried out regularly, would be satisfactory for all members of the family.For the high-risk groups of the community - namely, the very old who might develop fracture of the neck of the femur58 and the very young, in addition to women during pregnancy and lactation - when exposure to the sun is impractical, vitamin D supplementation in the form of medication is essential. A daily dose of 400IU is enough to prevent rickets at any age.59,60 Improvement of maternal vitamin D status will prevent neonatal hypocalcemia44 and will render unnecessary further supplementation for a breast-fed infant, and maintain bone mineralization for at least the first six months of life.43,55 Because of the prevailing environmental factors, it is recommended that women during pregnancy and lactation receive vitamin D supplements of 400-800 IU daily to prevent infantile rickets.There is no place for massive doses of vitamin D for prophylaxis. These can cause serious vitamin D toxicity in infants, manifested by hypercalcemia and renal failure.61,62 There may be more serious effects during pregnancy, resulting in a baby having congenital hypercalcemia and elfin facies.63TreatmentVitamin D3 in doses of 1,000 IU orally each day for three to four weeks will heal all grades of simple deficiency rickets at any age.15 When compliance is not assured, single-dose vitamin D3 orally in a dose of 150,000 to 600,000 IU (depending on age) is adequate and need not be repeated.ARTICLE REFERENCES:1. Hess A. "The history of rickets" . Rickets, including osteomalacia and tetany. Philadelphia: Lea and Febiger, 1929:22–37. Google Scholar2. Harrison HE, Harrison HC. "Rickets and osteomalacia" . Harrison HE, Harrison HC, eds. Disorders of calcium and phosphate metabolism in childhood and adolescence. Philadelphia: WB Saunders, 1979:146–50. Google Scholar3. Arneil GC, Crosbie JC. "Infantile rickets returns to Glasgow" . Lancet. 1963; 2:423–5. 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"Vitamin D intoxication: a case report and review of literature" . Ann Saudi Med. 1987; 7(2);157–60. Google Scholar63. Forfar JO, Balf CL, Maxwell GM, Tompsett SL. "Idiopathic hypercalcaemia of infancy: clinical and metabolic studies with special reference to the aetiological role of vitamin D" . Lancet. 1956; 1:981. Google Scholar Previous article Next article FiguresReferencesRelatedDetailsCited byBahakim H, Bamgboye E, Mahdi A, Al-Mugeiren M and Familusi J (2019) Pediatric Inpatients at the King Khalid University Hospital Riyadh, Saudi Arabia, 1985-1989, Annals of Saudi Medicine , 13:1, (8-13), Online publication date: 1-Jan-1993.Nabi G (2019) Vitamin D Deficiency Rickets in Riyadh, Annals of Saudi Medicine , 12:1, (108-109), Online publication date: 1-Jan-1992. Volume 7, Issue 2April 1987 Metrics History Accepted13 August 1986Published online1 April 1987 KeywordsRickets - Saudi ArabiaVitamin D deficiencyInformationCopyright © 1987, Annals of Saudi MedicinePDF download
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