RESUMO
Rickets results from impaired mineralization of growing bone due to alterations in calcium and phosphate homeostasis. Clinical signs of rickets are related to the age of the patient, the duration of the disease, and the underlying disorder. The most common signs of rickets are swelling of the wrists, knees or ankles, bowing of the legs (knock-knees, outward bowing, or both) and inability to walk. However, clinical features alone cannot differentiate between the various forms of rickets. Rickets includes a heterogeneous group of acquired and inherited diseases. Nutritional rickets is due to a deficiency of vitamin D, dietary calcium or phosphate. Mutations in genes responsible for vitamin D metabolism or function, the production or breakdown of fibroblast growth factor 23, renal phosphate regulation, or bone mineralization can lead to the hereditary form of rickets. This position paper reviews the relevant literature and presents the expertise of the Bone and Mineral Metabolism Group of the Italian Society of Pediatric Endocrinology and Diabetology (SIEDP). The aim of this document is to provide practical guidance to specialists and healthcare professionals on the main criteria for diagnosis, treatment, and management of patients with rickets. The various forms of rickets are discussed, and detailed references for the discussion of each form are provided. Algorithms to guide the diagnostic approach and recommendations to manage patients with rare forms of hereditary rickets are proposed.
Assuntos
Endocrinologia , Raquitismo , Humanos , Raquitismo/diagnóstico , Raquitismo/terapia , Raquitismo/metabolismo , Endocrinologia/métodos , Endocrinologia/normas , Itália , Vitamina D/metabolismo , Vitamina D/uso terapêutico , Criança , Sociedades Médicas/normas , Gerenciamento ClínicoRESUMO
Nutritional rickets, caused by vitamin D and/or calcium deficiency is by far the most common cause of rickets. In resource-limited settings, it is therefore not uncommon to treat rickets with vitamin D and calcium. If rickets fails to heal and/or if there is a family history of rickets, then refractory rickets should be considered as a differential diagnosis. Chronic low serum phosphate is the pathological hallmark of all forms of rickets as its low concentration in extracellular space leads to the failure of apoptosis of hypertrophic chondrocytes leading to defective mineralisation of the growth plate. Parathyroid hormone (PTH) and fibroblast growth factor 23 (FGF23) control serum phosphate concentration by facilitating the excretion of phosphate in the urine through their action on the proximal renal tubules. An increase in PTH, as seen in nutritional rickets and genetic disorders of vitamin D-dependent rickets (VDDRs), leads to chronic low serum phosphate, causing rickets. Genetic conditions leading to an increase in FGF23 concentration cause chronic low serum phosphate concentration and rickets. Genetic conditions and syndromes associated with proximal renal tubulopathies can also lead to chronic low serum phosphate concentration by excess phosphate leak in urine, causing rickets.In this review, authors discuss an approach to the differential diagnosis and management of refractory rickets.
Assuntos
Raquitismo Hipofosfatêmico Familiar , Raquitismo , Humanos , Cálcio , Fatores de Crescimento de Fibroblastos , Raquitismo/diagnóstico , Raquitismo/etiologia , Raquitismo/terapia , Vitamina D/uso terapêutico , Hormônio Paratireóideo , Vitaminas , Fosfatos , Raquitismo Hipofosfatêmico Familiar/diagnóstico , Raquitismo Hipofosfatêmico Familiar/terapiaRESUMO
Rickets is the disease of a growing skeleton and results from impaired apoptosis of hypertrophic chondrocytes and mineralization of the growth plate. Nutritionally induced rickets, secondary to vitamin D and/or calcium deficiency, remains a major global problem. In this review, we discuss pathogenesis, clinical signs, investigation and management of nutritional rickets.
Assuntos
Desnutrição , Raquitismo , Deficiência de Vitamina D , Humanos , Raquitismo/diagnóstico , Raquitismo/etiologia , Raquitismo/terapia , Vitamina D/uso terapêutico , Vitaminas , Deficiência de Vitamina D/complicações , CálcioRESUMO
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.
Assuntos
Raquitismo , Vitamina D , Animais , Cães , Humanos , Óleo de Fígado de Bacalhau/uso terapêutico , Raquitismo Hipofosfatêmico Familiar/genética , Raquitismo Hipofosfatêmico Familiar/história , Hormônio Paratireóideo , Raquitismo/genética , Raquitismo/história , Raquitismo/fisiopatologia , Raquitismo/terapia , Vitamina D/fisiologia , Vitamina D/uso terapêutico , VitaminasRESUMO
Rickets is one of the most prevalent non-communicable diseases in children in the developing world. It is often found in cultures in which children follow strict vegetarian diets and are not exposed to vitamin D-enhanced foods. While a rare occurrence, X-linked hypophosphatemic rickets may be the most frequent type of the disease seen outside the Third World today. However, there is not much credible information on the extent of the development of rickets. Therefore, pediatric nurses must be able to recognize children at risk and provide best practice care for the prevention and treatment of rickets. When caring for children in hospitals, communities or classrooms, nurses play a vital role in identifying children at risk for hypovitaminosis D and advising families to, if possible, follow safe diets and take supplements in order to avoid health complications associated with low levels of vitamin D. This study examines the prevalence and variables contributing to rickets, including hypovitaminosis vitamin D, the consequent orthopedic problems and the role of nurses in preventing and managing the pathogenesis of rickets and ultimately avoiding extreme deficits that result in bone deformities and the need for corrective surgery.
Assuntos
Raquitismo , Deficiência de Vitamina D , Criança , Suplementos Nutricionais , Humanos , Raquitismo/epidemiologia , Raquitismo/terapia , Vitamina D/uso terapêutico , Deficiência de Vitamina D/epidemiologia , VitaminasRESUMO
Kurt Huldschinsky (1883-1940) was a German pediatrician who was one of the international leaders in the field of rickets research between the two world wars. After his medical studies, he served at the Kaiserin-Auguste-Victoria-Haus in Berlin and at the University Children's Hospital in Vienna, among other places. After World War I, he worked with the famous orthopedist Konrad Biesalski at the Oskar-Helene-Heim for the healing and education of frail children in Berlin. Here he was the first to prove that exposure to ultraviolet (UV) radiation from mercury vapor lamps ("artificial sunlight") could cure rickets in young children, which is mostly caused by vitamin D deficiency. He published his discovery in this journal - the Deutsche Medizinische Wochenschrift [German Medical Weekly] - in 1919. For this groundbreaking scientific achievement and his further research into the prevention and treatment of rickets, Huldschinsky was awarded the Otto Heubner Prize of the German Association of Pediatrics in 1926. He was even nominated for the Nobel Prize in Medicine. As a Jew, however, he had to flee Germany from the National Socialists in 1933/34. Together with his wife and daughter, he emigrated to Egypt, where he died in Alexandria on October 31, 1940. As Huldschinsky was for many decades almost forgotten, this article recalls the life and work of a meritorious physician and scientist.
Assuntos
Pediatras/história , Raquitismo , Egito , Alemanha , História do Século XIX , História do Século XX , Humanos , Judaísmo , Masculino , Fototerapia , Raquitismo/história , Raquitismo/prevenção & controle , Raquitismo/terapia , II Guerra MundialRESUMO
AIM: To describe the demographic characteristics, risk factors, and presenting features of children with symptomatic nutritional rickets in France. METHODS: This is a retrospective study of 38 children diagnosed with nutritional rickets from 1998 to 2019. RESULTS: We observed a higher frequency of rickets in males (74 vs. 26%), in young children (median age at diagnosis: 23 months; 82% were younger than 5 years), and in children with a non-Caucasian ethnic background (89%). Most children were exclusively breastfed (78%) without adequate vitamin D supplementation (89%). The most common presentations were bowed legs (63%), hypocalcemic seizures (21%), and growth retardation (11%). Approximately half (62%) of the children were hypocalcemic. The children presenting with hypocalcemic seizures were significantly younger (0.8 vs. 2.2 years; p = 0.041) and had lower total serum calcium levels (1.44 vs. 2.17 mmol/L; p < 0.0001), higher phosphatemia (1.43 vs. 1.23 mmol/L; p = 0.020), and lower 25-hydroxy vitamin D levels (3 vs. 7 ng/mL; p = 0.020) but similar parathyroid hormone levels (357 vs. 289 ng/mL; p = 0.940) compared to rickets cases who did not experience hypocalcemic seizures. A dilated cardiomyopathy was detected in 14% of the children who had undergone echocardiography. CONCLUSION: Nutritional rickets remains endemic in the pediatric population and its most severe forms can have life-threatening sequelae. Health practitioners need to be cognizant of these facts to raise awareness and screen high-risk populations.
Assuntos
Raquitismo/epidemiologia , Adolescente , Conservadores da Densidade Óssea/uso terapêutico , Criança , Pré-Escolar , Feminino , França/epidemiologia , Humanos , Lactente , Masculino , Radiografia , Estudos Retrospectivos , Raquitismo/diagnóstico por imagem , Raquitismo/terapia , Fatores de Risco , Vitamina D/uso terapêuticoRESUMO
BACKGROUND: Nutritional rickets is a disease which affects children, especially in low- and middle-income countries. It causes problems such as skeletal deformities and impaired growth. The most common cause of nutritional rickets is vitamin D deficiency. Vitamin D administered with or without calcium is commonly regarded as the mainstay of treatment. In some sunny countries, however, where children are believed to have adequate vitamin D production from exposure to ultraviolet light, but who are deficient in calcium due to low dietary intake, calcium alone has also been used in the treatment of nutritional rickets. Therefore, it is important to compare the effects of vitamin D, calcium or a combination of vitamin D and calcium for the treatment of nutritional rickets in children living in different settings. OBJECTIVES: To assess the effects of vitamin D, calcium or a combination of vitamin D and calcium for the treatment of nutritional rickets in children. SEARCH METHODS: We searched CENTRAL, MEDLINE, LILACS, WHO ICTRP Search Portal and ClinicalTrials.gov. The date of the last search of all databases was 25 July 2019. We applied no language restrictions. SELECTION CRITERIA: We included randomised controlled trials (RCT) involving children aged 0 to 18 years with nutritional rickets which compared treatment with vitamin D, calcium or a combination of vitamin D and calcium. DATA COLLECTION AND ANALYSIS: Two review authors independently screened the title and abstracts of all studies, extracted data and assessed the risk of bias of included studies. We resolved any disagreements by consensus or recourse to a third review author. We conducted meta-analyses for the outcomes reported by study authors. For dichotomous outcomes, we calculated the risk ratio (RR) and 95% confidence interval (CI) and, for continuous outcomes, we calculated mean differences (MD) with 95% CIs. We assessed the certainty of the evidence of the included studies using GRADE. MAIN RESULTS: We identified 4562 studies; of these, we included four RCTs with 286 participants. The studies compared two or more of the following: vitamin D, calcium or vitamin D plus calcium. The number of participants randomised to receive vitamin D was 64, calcium was 102 and vitamin D plus calcium was 120. Two studies were conducted in India and two were conducted in Nigeria. None of the included studies had a low risk of bias in all domains. Three studies had a high risk of bias in at least one domain. The age of the participants ranged between six months and 14 years. The duration of follow-up ranged between 12 weeks and 24 weeks. Two studies compared vitamin D to calcium. There is low-certainty evidence that, at 24 weeks' follow-up, calcium alone improved the healing of rickets compared to vitamin D alone (RR 3.26, 95% CI 1.59 to 6.69; P = 0.001; 1 study, 71 participants). Comparing vitamin D to calcium showed no firm evidence of an advantage or disadvantage in reducing morbidity (fractures) (RR 0.27, 95% CI 0.03 to 2.32; P = 0.23; 1 study, 71 participants; very low-certainty evidence). Adverse events were not reported. Two studies compared vitamin D plus calcium to vitamin D at 12 or 24 weeks. Vitamin D plus calcium improved healing of rickets compared to vitamin D alone at 24 weeks' follow-up (RR 3.06, 95% CI 1.49 to 6.29; P = 0.002; 1 study, 75 participants; low-certainty evidence). There is no conclusive evidence in favour of either intervention for reducing morbidity (fractures) (RR 0.24, 95% CI 0.03 to 2.08; P = 0.20; 1 study, 71 participants; very low-certainty evidence) or adverse events (RR 4.76, 95% CI 0.24 to 93.19; P = 0.30; 1 study, 39 participants; very low-certainty evidence). All four included studies compared vitamin D plus calcium to calcium at different follow-up times. There is no conclusive evidence on whether vitamin D plus calcium in comparison to calcium alone improved healing of rickets at 24 weeks' follow-up (RR 1.17, 95% CI 0.72 to 1.90; P = 0.53; 2 studies, 140 participants; very low-certainty evidence). Evidence is also inconclusive for morbidity (fractures) (RR 0.89, 95% CI 0.06 to 13.76; P = 0.94; 1 study, 72 participants; very low-certainty evidence) and adverse events (RR 4.29, 0.22 to 83.57; P = 0.34; 1 study, 37 participants; very low-certainty evidence). Most of the evidence in the review is low or very low certainty due to risk of bias, imprecision or both. None of the included studies assessed all-cause mortality, health-related quality of life or socioeconomic effects. One study assessed growth pattern but this was not measured at the time-point stipulated in the protocol of our review (one or more years after commencement of therapy). AUTHORS' CONCLUSIONS: This review provides low-certainty evidence that vitamin D plus calcium or calcium alone improve healing in children with nutritional rickets compared to vitamin D alone. We are unable to make conclusions on the effects of the interventions on adverse events or morbidity (fractures).
Assuntos
Cálcio/uso terapêutico , Raquitismo/terapia , Vitamina D/uso terapêutico , Vitaminas/uso terapêutico , Adolescente , Criança , Pré-Escolar , Fraturas Ósseas/epidemiologia , Fraturas Ósseas/prevenção & controle , Humanos , Lactente , Ensaios Clínicos Controlados Aleatórios como Assunto , Raquitismo/etiologia , Deficiência de Vitamina D/complicações , Deficiência de Vitamina D/terapiaRESUMO
The review provides a historical perspective on the convergence of our understanding of the physiology and pathophysiology of bone, calcium, phosphorus, vitamin D, parathyroid hormone, and FGF-23 their impact on rickets.
Assuntos
Osso e Ossos/fisiopatologia , Raquitismo/etiologia , Animais , Osso e Ossos/metabolismo , Cálcio da Dieta/metabolismo , Modelos Animais de Doenças , Fator de Crescimento de Fibroblastos 23 , Fatores de Crescimento de Fibroblastos/metabolismo , História do Século XIX , História do Século XX , História do Século XXI , Humanos , Hormônio Paratireóideo/metabolismo , Fósforo/metabolismo , Raquitismo/história , Raquitismo/fisiopatologia , Raquitismo/terapia , Vitamina D/metabolismoAssuntos
Ictiose Lamelar/genética , Raquitismo/genética , Transglutaminases/genética , Adolescente , Cálcio/administração & dosagem , Códon sem Sentido , Suplementos Nutricionais , Efeito Fundador , Humanos , Ictiose Lamelar/complicações , Ictiose Lamelar/diagnóstico , Masculino , Raquitismo/diagnóstico , Raquitismo/terapia , Luz Solar , Tunísia , Vitamina D/administração & dosagemRESUMO
This study was designed to evaluate the effect of pulsed signal therapy (PST) on patellofemoral pain syndrome associated with patellar chondropathy. A prospective randomized double-blind placebo controlled trial included 25 patients (41 knees) between 20 and 50 years with pain due to isolated patellofemoral syndrome with chondropathy. PST group received nine 60-min daily sessions of PST treatment. Control group received the same protocol of blinded placebo treatment. The main outcome was change from baseline Kujala score at 3 months. After 3 months, patients in the control group received effective treatment (placebo post-treatment). All patients were then followed, for up to 12 months. Seventeen knees (5 males and 12 females, mean age 36.7 ± 7.9) received placebo and 24 knees (8 males and 16 females, mean age 35.5 ± 8.9) received PST. By the third month, PST group exhibited a mean change from baseline of 9.63 ± 7.5 Kujala points, compared to 0.53 ± 1.8 in the placebo group (P < 0.001). A significant progressive improvement was seen in the PST group between the 3rd and 6th and between the 6th and 12th month (P < 0.016). Patients initially allocated in the control group also improved at 3 months (P < 0.001) and 6 months (P = 0.005) post-effective treatment. In conclusion, PST in patellofemoral pain syndrome with chondropathy was effective compared to placebo at 3 months, showing an important improvement of Kujala score. The improvement was progressive and maintained up to 12 months. PST is safe and should be considered as a non-invasive option for management of this condition. Bioelectromagnetics. 40:83-90, 2019. © 2019 Bioelectromagnetics Society.
Assuntos
Magnetoterapia/métodos , Patela/lesões , Síndrome da Dor Patelofemoral/terapia , Raquitismo/terapia , Adulto , Método Duplo-Cego , Campos Eletromagnéticos , Feminino , Fêmur/patologia , Humanos , Artropatias/tratamento farmacológico , Joelho , Masculino , Pessoa de Meia-Idade , Medição da Dor , Síndrome da Dor Patelofemoral/complicações , Resultado do TratamentoRESUMO
PURPOSE: After Glisson's description of rickets, it took two centuries to realize that rickets was due to the absence of antirachitic nutrients in the diet or lack exposure of the skin to ultraviolet rays. This bone disease caused by vitamin D deficiency was one of the most common diseases of children 100 years ago. This paper explores how the definition, diagnosis, and treatment of rickets shifted in the first decades of the twentieth century. MATERIAL AND METHODS: Although benefits of cod liver oil as food were known as early as the seventh century, cod liver oil was only proposed as medicinal for rickets in Northern Europe at the end of the eighteenth century. The relationship between rickets and nutritional deficiency was suspected and demonstrated between 1880 and 1915, at the same time of the discovery of other vital substances (vitamins) needed to prevent beriberi, scurvy, and pellagra. Understanding that the lack of photosynthesized vitamin D or the lack of dietary vitamin D was a similar risk of rickets was an important turn in the comprehension of the disease. We look at the sequence and turn of events related to the discovery of vitamin D. RESULTS: Rickets has been recognized first as a disease of urban living people. Cod liver oil had been used since 1700 as a nonspecific treatment for a range of diseases. Generations of children in cities of the north of Europe had learned to hate the taste and smell of the black oily liquid and then grown up to be parents who, in turn, hated to force it down their children's throats. Occasional papers before 1900 pointed to its efficacy for rickets, and most textbooks of the early 1900s mentioned it only as a treatment option. The discovery in the early 1900s that artificial and natural ultraviolet rays had both antirachitic activity allowed to produce antirachitic foods just by food irradiation with artificial ultraviolet irradiation. Clinical guidelines were adopted to propose exposure to sunlight or to artificial ultraviolet radiation to prevent rickets in children. By the mid-1920s, rickets was promoted as universal, at times invisible to non-experts, but present to some degree in nearly every young child regardless of race or class. It was thus used to promote the young disciplines of preventive medicine, pediatrics, and public health. Innovative advances were made in the understanding of vitamin D synthesis from 1915 to 1935. A public health campaign of the 1930s was a success to eradicate rickets, using irradiated ergosterol from yeast to enrich milk and other foods with vitamin D, ensuring that the general population was consuming sufficient vitamin D. CONCLUSION: Rickets therefore provides an excellent window into the early politics of preventive health and the promotion of targeted interventions in the world. It is also a relevant historical counterpoint for current debates over the role of risk factors (absence of light or sun) for disease (today's so-called "lifestyle" diseases).
Assuntos
Óleo de Fígado de Bacalhau/história , Raquitismo/história , Terapia Ultravioleta/história , Deficiência de Vitamina D/história , Animais , Óleo de Fígado de Bacalhau/uso terapêutico , Europa (Continente) , História do Século XVII , História do Século XIX , História do Século XX , História Antiga , Humanos , Raquitismo/diagnóstico , Raquitismo/etiologia , Raquitismo/terapia , Raios Ultravioleta/história , Vitamina D/história , Vitamina D/uso terapêutico , Deficiência de Vitamina D/complicações , Deficiência de Vitamina D/diagnóstico , Deficiência de Vitamina D/terapiaRESUMO
Severe vitamin D deficiency can be defined as the dose of vitamin D or serum 25OHD concentrations needed to prevent nutritional rickets or osteomalacia. There is large international consensus that these diseases can be prevented by 400 IU of vitamin D/d and 25OHD above 30 nmol/l (12 ng/ml). Vitamin D deficiency can also accelerate the risk of fractures and probably also of falls in elderly subjects but there is no consensus on the required daily doses or minimal 25OHD threshold for these endpoints. The majority of experts consider 800 IU/d and serum 25OHD above 50 nmol/l (20 ng/ml) as sufficient, with a minority opinion aiming for 75 nmol/l or even higher. For other extra-skeletal endpoints, no hard evidence is available to define whether or not this is causally related to vitamin D status. Therefore, for these endpoints no minimal dosage or 25OHD threshold can be defined.
Assuntos
Deficiência de Vitamina D/diagnóstico , Deficiência de Vitamina D/terapia , Idoso , Idoso de 80 Anos ou mais , Fraturas Ósseas/epidemiologia , Fraturas Ósseas/prevenção & controle , Fraturas Ósseas/terapia , Humanos , Raquitismo/diagnóstico , Raquitismo/epidemiologia , Raquitismo/etiologia , Raquitismo/terapia , Vitamina D/sangue , Deficiência de Vitamina D/sangue , Deficiência de Vitamina D/epidemiologia , Vitaminas/sangueRESUMO
The vitamin D history started early in the evolution of life (billion years ago) as a photochemical reaction producing an inert molecule. During the early evolution of vertebrates, this molecule became essential for calcium and bone homeostasis of terrestrial animals and arrived to the status of hormone. Phytoplankton, zooplankton, and most plants and animals that are exposed to sunlight have the capacity to make vitamin D. Vitamin D is critically important for the development, growth, and maintenance of a healthy skeleton from birth until death. The major function of vitamin D is to maintain calcium homeostasis. It accomplishes this by increasing the efficiency of the intestine to absorb dietary calcium. When there is inadequate calcium in the diet to satisfy the body's calcium requirement, vitamin D communicates to the osteoblasts that signal osteoclast precursors to mature and dissolve the calcium stored in the bone. The typical "vitamin D-deficiency" disorder was observed for growing children in the west and south of England in the early 1600s. This disease was described by Glisson and named "rickets" (known also as "the English disease") and was observed with epidemic proportions in northern Europe and North America. The corrections of deformities of rickets were at the origin of the name "orthopedia" and of the technique of osteotomies.
Assuntos
Raquitismo/história , Vitamina D/história , Animais , Criança , História do Século XVII , História do Século XVIII , História do Século XIX , História do Século XX , Humanos , Plâncton , Raquitismo/terapia , Esqueleto/fisiologia , Vitamina D/fisiologiaRESUMO
The effects of rickets on children recovery from severe acute malnutrition (SAM) are unknown. Rickets may affect both growth and susceptibility to infectious diseases. We investigated the associations of clinically diagnosed rickets with life-threatening events and anthropometric recovery during 1 year following inpatient treatment for complicated SAM. This was a secondary analysis of clinical trial data among non-human immunodeficiency virus-infected Kenyan children with complicated SAM (2-59 months) followed for 1 year posthospital discharge (ClinicalTrials.gov ID NCT00934492). The outcomes were mortality, hospital readmissions, and growth during 12 months. The main exposure was clinically diagnosed rickets at baseline. Of 1,778 children recruited, 230 (12.9%, 95% CI [11.4, 14 .6]) had clinical signs of rickets at baseline. Enrolment at an urban site, height-for-age and head circumference-for-age z scores were associated with rickets. Rickets at study enrolment was associated with increased mortality (adjusted Hazard Ratio [aHR] 1.61, 95% CI [1.14, 2.27]), any readmission (aHR 1.37, 95% CI [1.09, 1.72]), readmission for severe pneumonia (aHR 1.37, 95% CI [1.05, 1.79]), but not readmission with diarrhoea (aHR 1.05, 95% CI [0.73, 1.51]). Rickets was associated with increased height gain (centimetres), adjusted regression coefficient 0.19 (95% CI [0.10, 0.28]), but not changes in head circumference, mid-upper arm circumference, or weight. Rickets was common among children with SAM at urban sites and associated with increased risks of severe pneumonia and death. Increased height gain may have resulted from vitamin D and calcium treatment. Future work should explore possibility of other concurrent micronutrient deficiencies and optimal treatment of rickets in this high-risk population.
Assuntos
Transtornos da Nutrição Infantil/epidemiologia , Transtornos do Crescimento/epidemiologia , Raquitismo/epidemiologia , Doença Aguda , Transtornos da Nutrição Infantil/dietoterapia , Pré-Escolar , Comorbidade , Método Duplo-Cego , Feminino , Humanos , Lactente , Quênia/epidemiologia , Masculino , Raquitismo/terapia , Índice de Gravidade de DoençaRESUMO
Although the intestine plays the major role in 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] action on calcium homeostasis, the mechanisms involved remain incompletely understood. The established model of 1,25(OH)2D3-regulated intestinal calcium absorption postulates a critical role for the duodenum. However, the distal intestine is where 70% to 80% of ingested calcium is absorbed. To test directly the role of 1,25(OH)2D3 and the vitamin D receptor (VDR) in the distal intestine, three independent knockout (KO)/transgenic (TG) lines expressing VDR exclusively in the ileum, cecum, and colon were generated by breeding VDR KO mice with TG mice expressing human VDR (hVDR) under the control of the 9.5-kb caudal type homeobox 2 promoter. Mice from one TG line (KO/TG3) showed low VDR expression in the distal intestine (<50% of the levels observed in KO/TG1, KO/TG2, and wild-type mice). In the KO/TG mice, hVDR was not expressed in the duodenum, jejunum, kidney, or other tissues. Growth arrest, elevated parathyroid hormone level, and hypocalcemia of the VDR KO mice were prevented in mice from KO/TG lines 1 and 2. Microcomputed tomography analysis revealed that the expression of hVDR in the distal intestine of KO/TG1 and KO/TG2 mice rescued the bone defects associated with systemic VDR deficiency, including growth plate abnormalities and altered trabecular and cortical parameters. KO/TG3 mice showed rickets, but less severely than VDR KO mice. These findings show that expression of VDR exclusively in the distal intestine can prevent abnormalities in calcium homeostasis and bone mineralization associated with systemic VDR deficiency.
Assuntos
Ceco/metabolismo , Colo/metabolismo , Terapia Genética , Íleo/metabolismo , Receptores de Calcitriol/genética , Raquitismo/genética , Raquitismo/terapia , Animais , Células CACO-2 , Calcificação Fisiológica/genética , Cálcio/metabolismo , Ceco/patologia , Colo/patologia , Feminino , Terapia Genética/métodos , Humanos , Íleo/patologia , Absorção Intestinal/genética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Receptores de Calcitriol/metabolismo , Raquitismo/metabolismo , Raquitismo/patologiaRESUMO
The European Society of Endocrinology has published this year a series of guidelines for hypoparathyroidism, the management of adrenal incidentalomas as well as for the long-term follow-up of patients operated on for a phaeochromocytoma/paraganglioma (PPGL). For hypoparathyroidism, guidelines insist on screening for chronic complications and monitoring treatment with calcium and vitamin D; the use of recombinant PTH may provide new opportunities for the future. Concerning adrenal incidentalomas, the panel of the guidelines primarily recommends non contrast CT for the evaluation of the risk of malignancy. Patients operated on for a PPGL, should be offered an individualized follow-up plan based on assessment of their risk of tumor recurrence.
Des nouvelles recommandations concernant l'hypoparathyroïdie, l'évaluation des incidentalomes surrénaliens ainsi que le suivi à long terme des patients opérés d'un phéochromocytome/paragangliome (PPGL), ont été publiées en 2016 par la Société européenne d'endocrinologie. Pour l'hypoparathyroïdie, l'accent est mis sur l'évaluation des complications chroniques et la titration du traitement par calcium et vitamine D; la supplémentation par PTH-recombinante (rhPTH) est un traitement prometteur. Concernant l'évaluation du risque de malignité des incidentalomes surrénaliens, les études montrent une supériorité de la densité spontanée (DS) de ces tumeurs au CT-scan non injecté, en tant que critère diagnostique. Enfin, un suivi personnalisé est indiqué pour les patients opérés d'un PPGL, après évaluation du risque de récidive à long terme.
Assuntos
Endocrinologia/tendências , Neoplasias das Glândulas Suprarrenais/terapia , Endocrinologia/métodos , Humanos , Hipoparatireoidismo/terapia , Monitorização Fisiológica , Paraganglioma/terapia , Feocromocitoma/terapia , Cuidados Pós-Operatórios/métodos , Raquitismo/terapiaRESUMO
BACKGROUND: A female infant was admitted to hospital due to failure to thrive. She presented hypercalcemia (4.09 mmol/L, normal range: 2.2-2.65 mmol/L), high 25-hydroxyvitamin D (283 nmol/L, normal range: 75-250 nmol/L), 1,25-dihydroxyvitamin D in the upper normal range, and low parathyroid hormone. Vitamin D intoxication was suspected. The patient had received routine rickets prophylaxis. METHODS: Williams-Beuren syndrome was genetically excluded. Sequencing of CYP24A1 showed 2 mutations: c.443T>C and c.1186C>T. RESULTS: The patient's clinical status improved after intravenous rehydration, cessation of supplementation, and on a low-calcium diet. 25-Hydroxyvitamin D concentrations normalized within days, while 1,25-dihydroxyvitamin D remained in the upper normal range. We also investigated our patient's bone health. CONCLUSION: The patient was hospitalized initially on suspicion of vitamin D intoxication but proved to be a case of compound heterozygosity. Data on the long-term clinical and biochemical evolution of patients with idiopathic infantile hypercalcemia are sparse. Our follow-up showed seasonal variations of vitamin D and calcium parameters, with no influence on kidney function or bone health for the investigated period.
Assuntos
Hipercalcemia/genética , Hipercalcemia/terapia , Mutação Puntual , Raquitismo/genética , Raquitismo/terapia , Vitamina D3 24-Hidroxilase/genética , Pré-Escolar , Feminino , Seguimentos , Humanos , Lactente , Vitamina D3 24-Hidroxilase/metabolismoRESUMO
Worldwide, nutritional rickets continues to be an evolving problem with several causes. This paper provides an updated literature review characterising the prevalence, aetiology, pathophysiology and treatment of nutritional rickets worldwide. A systematic review of articles on nutritional rickets from various geographical regions was undertaken. For each region, key information was extracted, including prevalence, cause of rickets specific to the region, methods of confirming the diagnosis and current treatment and preventive measures. Calcium deficiency continues to be a major cause of rickets in Africa and Asia. Vitamin D deficiency rickets is perhaps increasing in the Americas, Europe and parts of the Middle East. There continues to be a distinct presentation of calcium-predominant versus vitamin D predominant rickets, although there are overlapping features. More careful diagnosis of rickets and reporting of 25-OHD concentrations has improved accurate knowledge of rickets prevalence and better delineated the cause. Nutritional rickets continues to be an evolving and multi-factorial problem worldwide. It is on a spectrum, ranging from isolated vitamin D deficiency to isolated calcium deficiency. Specific areas which require emphasis include a consistent community approach to screening and diagnosis, vitamin D supplementation of infants and at-risk children, prevention of maternal vitamin D deficiency and the provision of calcium in areas with low calcium diets.