25-Hydroxycholecalciferol. A COMPARATIVE STUDY IN DEFICIENCY RICKETS AND DIFFERENT TYPES OF RESISTANT RICKETS

The effects of 25-hydroxycholecalciferol were studied in 4 children with deficiency rickets and 22 children with D-resistant rickets, including patients with hereditary hypophosphatemic D-resistant rickets, "pseudo-deficiency" rickets, and rickets secondary to cystinosis or to tyrosinosis. Three protocols were used. (a) 8 days after a single oral dose of 16,000 IU of 25-hydroxycholecalciferol, normalization of all biological parameters was observed in all cases of deficiency rickets. A complete lack of response was observed in the different types of resistant rickets. (b) Under prolonged administration of 2,640 IU/day for 2 months, clinical-biological symptoms and X-ray lesions disappeared, and a catch-up growth pattern was observed in deficiency rickets; no relapse of rickets occurred up to 5 months after therapy was stopped. The same dose had no significant effect in 10 patients with hereditary hypophosphatemic D-resistant rickets. A bone biopsy performed in one case showed the persistence of characteristic lesions. (c) With increasing doses of 25-hydroxycholecalciferol varying from 6,000 to 30,000 IU/day and a follow-up of 6 months up to 2 yr duration, clinical-biological-radiologic recovery and catch-up growht was obtained in all cases of "pseudo-deficiency" rickets. In hypophosphatemic hereditary D-resistant rickets, 5 out of 13 patients' serum concentration of phosphorus reached at least 30 mg/liter, but a catch-up growth pattern was not observed. These results indicate that (a) 25-hydroxycholecalciferol is highly active in deficiency rickets; (b) a defect in the conversion of vitamin D(3) to its active 25-hydroxy metabolite is probably not the metabolic defect in any of the different types of vitamin D-resistant rickets studied.     

The importance of limited exposure to ultraviolet radiation and dietary factors in the aetiology of Asian rickets: a risk-factor model

Regional variation in the prevalence of Asian rickets was examined in Coventry, Bradford and Glasgow. Records of 152 weeks of daylight outdoor exposure were obtained from 104 Glasgow Asian children, 53 of whom had been treated for rickets. Records of seven-day weighed dietary intake were obtained from 84 Asian children, 43 of whom had been treated for rickets. There was a marked north-south gradient in the prevalence of Asian rickets. In all cases of severe rickets with deformity the child was vegetarian. Severe rickets was associated with lower intake of meat, higher intake of chapati and lower daylight outdoor exposure values than in normal children. Multivariate analysis employing a combination of these variables provided good separation between rachitic and normal groups. A risk-factor model is proposed which suggests that regional variation in the prevalence of rickets among Asian communities in Britain is mainly determined by the effects of latitude and the nature of the urban environment on available ultraviolet radiation. Where UV radiation is restricted, individual propensity to rickets within a given Asian community is mainly determined by dietary factors.     

Rickets: not a disease of the past

Rickets develops when growing bones fail to mineralize. In most cases, the diagnosis is established with a thorough history and physical examination and confirmed by laboratory evaluation. Nutritional rickets can be caused by inadequate intake of nutrients (vitamin D in particular); however, it is not uncommon in dark-skinned children who have limited sun exposure and in infants who are breastfed exclusively. Vitamin D-dependent rickets, type I results from abnormalities in the gene coding for 25(OH)D3-1-alpha-hydroxylase, and type II results from defective vitamin D receptors. The vitamin D-resistant types are familial hypophosphatemic rickets and hereditary hypophosphatemic rickets with hypercalciuria. Other causes of rickets include renal disease, medications, and malabsorption syndromes. Nutritional rickets is treated by replacing the deficient nutrient. Mothers who breastfeed exclusively need to be informed of the recommendation to give their infants vitamin D supplements beginning in the first two months of life to prevent nutritional rickets. Vitamin D-dependent rickets, type I is treated with vitamin D; management of type II is more challenging. Familial hypophosphatemic rickets is treated with phosphorus and vitamin D, whereas hereditary hypophosphatemic rickets with hypercalciuria is treated with phosphorus alone. Families with inherited rickets may seek genetic counseling. The aim of early diagnosis and treatment is to resolve biochemical derangements and prevent complications such as severe deformities that may require surgical intervention.     

The Importance of Limited Exposure to Ultraviolet Radiation and Dietary Factors in the Aetiology of Asian Rickets: A Risk-factor Model

Regional variation in the prevalence of Asian rickets was examinedin Coventry, Bradford and Glasgow. Records of 152 weeks of daylightoutdoor exposure were obtained from 104 Glasgow Asian children,53 of whom had been treated for rickets. Records of seven-dayweighed dietary intake were obtained from 84 Asian children,43 of whom had been treated for rickets. There was a marked north-south gradient in the prevalence ofAsian rickets. In all cases of severe rickets with deformitythe child was vegetarian. Severe rickets was associated withlower intake of meat, higher intake of chapati and lower daylightoutdoor exposure values than in normal children. Multivariateanalysis employing a combination of these variables providedgood separation between rachitic and normal groups. A risk-factor model is proposed which suggests that regionalvariation in the prevalence of rickets among Asian communitiesin Britain is mainly determined by the effects of latitude andthe nature of the urban environment on available ultravioletradiation. Where UV radiation is restricted, individual propensityto rickets within a given Asian community is mainly determinedby dietary factors.     

Metabolism of Vitamin D3-3H in Vitamin D-Resistant Rickets and Familial Hypophosphatemia

The fate of an intravenous dose of tritiated vitamin D(3) was studied in seven normal subjects, four children with vitamin D-resistant rickets, and four adults with a familial history of vitamin D-resistant rickets and persistent hypophosphatemia. An abnormal metabolism of vitamin D in vitamin D-resistant rickets was defined and characterized by a decrease in the plasma fractional turnover rate, a marked increase in plasma water-soluble metabolites, and a relative decrease in the conversion of vitamin D to a polar, biologically active metabolite. Alterations in vitamin D metabolism in the adults with persistent hypophosphatemia were similar but less severe than those of affected children with vitamin D-resistant rickets. It is tentatively concluded that the abnormalities in vitamin D metabolism documented in patients with vitamin D-resistant rickets and familial hypophosphatemia may account for the observed osseous and biochemical changes.     

EXPERIMENTAL RICKETS IN RATS : I. A DIET PRODUCING RICKETS IN WHITE RATS,AND ITS PREVENTION BY THE ADDITION OF AN INORGANIC SALT.

1. A simple diet is presented which regularly induced rickets in young rats. 2. The substitution of 0.4 per cent secondary potassium phosphate for a small part of calcium lactate in this diet completely inhibited the development of rickets. 3. Quantitative determinations of calcium in the bodies of parallel rats showed a marked increase of calcium content in the rats receiving the added phosphate over those which developed rickets. 4. While it is thus shown by x-rays and by histological examinations and by quantitative chemical analysis that added potassium phosphate increased the assimilation and normal deposition of calcium, it may be the quantitative relationship between the inorganic ions rather than actual deficiency of any one of them which was here the determining factor in the cause or prevention of rickets. Our experiments and conclusions do not exclude the possibility of other causes of rickets than those here discussed.     

Therapeutic use of vitamin D and its analogues for rickets and osteomalacia]

Recently, It has become clear that the mutant gene in X-linked hypophosphatemic rickets, vitamin D dependent rickets type I, and vitamin D dependent rickets type II were identified and they were caused by the disorder in the activation of vitamin D and the intracellular defect in vitamin D receptor. In this paper, the pathophysiology in various type of rickets or osteomalacia and the treatment by vitamin D agents were reported. So far, 1, alpha-(OH) D3 and 1, 25-(OH)2D3 have been effectively used as the treatment of these disease. However, vitamin D poisoning caused by these agents is still a serious issue for the treatment. In the near future, more effective treatment using genetic engineering is expected to treat the disorder of phosphate metabolism in X-linked hypophosphatemic rickets.     

儿童热性惊厥、佝偻病及缺铁性贫血的相关性研究

目的：探讨儿童热性惊厥、佝偻病与缺铁性贫血的关系。方法：将我院自2011年1月-2012年12月期间收治188例患儿分为热性惊厥组、发热组、佝偻病组、无佝偻病组各47例,比较各组相关指标。结果：热性惊厥组佝偻病的发病率高于发热组（P〈0．01）,佝偻病组的热性惊厥高于无佝偻病组（P〈0．05）;血红蛋白与25一OH—D3、惊厥次数的简单相关系数为0．7477和0．6544,P均〈0．05,25-OH—D3与惊厥次数的简单相关系数为0．8754。P〈0．01。结论：小儿热性惊厥及佝偻病均与缺铁性贫血存在一定的相关性。     

NITROGEN,POTASSIUM, SODIUM,AND CHLORINE METABOLISM IN RICKETS,WITH SPECIAL REFERENCE TO BILIARY FISTULA RICKETS IN PUPPIES

1. Rickets developed in three puppies deprived of vitamin D and sunlight since birth, in which, at the age of 6 to 7 weeks gall bladder fistula was established. The results of studies of their bones and of the calcium and phosphate metabolism have previously been published (2). Studies on the nitrogen, potassium, sodium, and chlorine metabolism, here presented, reveal that the metabolism was greatly interfered with as compared with that in three controls without gall bladder fistula rickets. This interference, together with an inhibited gain in weight, demonstrates that the pathogenesis of biliary, fistula rickets in puppies has to be considered distinctly different from infantile rickets as well as from rickets produced in rats. 2. The nitrogen, potassium, sodium, and chlorine metabolism was also studied in three rachitic and four healthy infants, and in eleven rachitic and six control rats. The balance of these substances, as well as their distribution in stool and urine, proved to be the same whether or not rickets was present. 3. The pathogenesis of biliary fistula rickets is discussed on the basis of these studies. The assumption has been made that deficiency in other vitamins than vitamin D might have a bearing upon the development of this disease. Further study with a view to possible elimination of these unspecific factors might lead to the experimental production by gall bladder fistula of a purely rachitic state. 4. The normal balance and distribution of nitrogen, potassium, sodium, and chlorine in the stool and urine of rachitic infants and rats are considered further evidence of the hypothetical nature of the so called absorption theory in infantile rickets.     

Increasing Incidence of Nutritional Rickets: A Population-Based Study in Olmsted County,Minnesota

ObjectiveTo determine temporal trends in incidence and risk factors of nutritional rickets in a community-based population.Patients and MethodsRochester Epidemiology Project data were used to identify all children (aged <18 years) residing in Olmsted County, Minnesota, between January 1, 1970, and December 31, 2009, with diagnostic codes corresponding to rickets, vitamin D deficiency, hypovitaminosis D, rachitis, osteomalacia, genu varum, genu valgum, craniotabes, hypocalcemia, hypocalcemic seizure, and tetany. Record abstraction was performed to select individuals with radiographic confirmation of rickets. Age- and sex-matched controls were identified for the evaluation of risk factors. The main outcome measure was radiographic evidence of rickets without identifiable inherited, genetic, or nonnutritional causes. Incidence rates were calculated using Rochester Epidemiology Project census data.ResultsOf 768 children with eligible diagnostic codes, 23 had radiographic evidence of rickets; of these, 17 children had nutritional rickets. All 17 children were younger than 3 years, and 13 (76%) were of nonwhite race/ethnicity. Clinical presentation included poor growth (n=12), leg deformity (n=8), motor delay (n=5), leg pain (n=3), weakness (n=3), and hypocalcemia or tetany (n=2). The incidence of nutritional rickets in children younger than 3 years was 0, 2.2, 3.7, and 24.1 per 100,000 for the decades beginning in 1970, 1980, 1990, and 2000, respectively (P=.003 for incidence trend). Nutritional rickets was associated with black race, breast-feeding, low birth weight, and stunted growth (P<.05 for all). Four of 13 patients (31%) who underwent 25-hydroxyvitamin D testing had values less than 10 ng/mL.ConclusionNutritional rickets remains rare, but its incidence has dramatically increased since 2000. Not all cases of rickets can be attributed to vitamin D deficiency.     

Incidental radiological diagnosis of rickets

Rickets fortunately remains rare in the United Kingdom, although its actual incidence is currently undetermined.1 Many still consider it to be a disease of poverty prevalent during the Victorian era. However, a number of recent articles have highlighted concern among British health professionals about the number of cases still being diagnosed in this country. These cases have nearly all involved non-Caucasian children who are considered to be at high risk due to skin colour, prolonged breast feeding, and low maternal vitamin D levels. Their presentations are variable ranging from failure to thrive, bone deformities, seizures, and even stridor. The diagnosis is usually made in babies and toddlers.We present a series of patients attending our accident and emergency (A&E) department, over a five month period, where the diagnosis of rickets was primarily a radiological diagnosis.     

热性惊厥患儿体内佝偻病相关指标的临床研究

目的:探讨热性惊厥与佝偻病的相关性.方法:选取2009年1月~2011年12月我院门诊/住院3月~3岁儿童120名作为研究对象,其中热性惊厥组、发热组和正常对照组各40例,检测和比较三组佝偻病患病率及其体内血钙、25-(OH)-D3、碱性磷酸酶及骨密度指标.结果:热性惊厥组佝偻病发病率显著高于较对照组及发热组,P均<0.01,且处于活动期佝偻病患儿数目也较其他两组多;热性惊厥组血钙、25-(OH)-D3、碱性磷酸酶及骨密度显著低于对照组及发热组,P均<0.05,而血清碱性磷酸酶浓度则显著高于对照组及发热组,P <0.01和P <0.05.结论:热性惊厥患儿佝偻病患病率及佝偻病相关指标异常程度增高,热性惊厥与佝偻病存在一定相关性.     

Hypocalcaemic fit in an adolescent boy with undiagnosed rickets

Rickets in early childhood has been well documented in the literature. We present a case report on a teenage Somalian boy who had a generalised tonic clonic fit (an unusual presentation of rickets in late childhood) and was diagnosed with vitamin D deficient rickets.     

Rickets

Nutritional (vitamin D deficiency) rickets is now a rarity in the industrial world because of food fortification. Most cases result from hereditary inborn errors of vitamin D metabolism or end-organ unresponsiveness as is exemplified in this case of hypophosphatemic rickets.     

维生素D受体基因多态性与婴幼儿佝偻病易感性的研究

目的 研究维生素D受体基因多态性与婴幼儿佝偻病易感性的相关性,为临床探索新的诊治途径提供理论依据.方法 采用病例对照研究,选择兰州大学第一医院儿内科确诊的佝倭病患儿56例(佝偻病组)和正常婴幼儿76例(正常对照组)作为研究对象.应用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)分析检测VDR基因BsmI位点的多态性,比较2组之间的VDR基因型和等位基因频率.结果 佝偻病组和正常对照组VDR基因BsmI位点基因型分布频率分别为BB 3.6%(2/56)、Bb 21.4%(12/56)、bb 75.0%(42/56)和BB 1.3%(1/76)、Bb 18.4%(14/76)、bb 80.3%(61/76),2组之间的差异无统计学意义(χ20.521,P>0.05);佝偻病组和正常对照组的VDR基因BsmI位点等位基因分布频率分别为B 14.3%(16/112)、b 85.7%(96/112)和B 10.5%(16/152)、b 89.5%(134/152),2组之间差异无统计学意义(χ20.783,P>0.05);多项分类Logistic回归分析结果 显示在调整了其他危险因素后,BsmI位点多态性未进入婴幼儿佝偻病发病因素的回归方程.方法 VDR基因BsmI位点的多态性可能与婴幼儿佝偻病遗传易感性无关.     

骨源性碱性磷酸酶检测对维生素D缺乏性佝偻病的诊疗意义

目的 探讨骨源性碱性磷酸酶的测定对维生素D缺乏性佝偻病的诊疗意义。方法 采用全血干化学免疫浓缩法对246例拟诊为维生素D缺乏性佝偻病患者进行骨源性碱性磷酸酶测定，根据检测结果采用适当的治疗方法。结果 全部病例症状消失，体征减轻，最终全部治愈。结论 骨源性碱性磷酸酶检测简便、快速、特异、结果可靠，对临床诊断维生素D缺乏性佝偻病极具指导价值。     

超声骨密度检测早期儿童佝偻病的临床应用价值分析

【】目的：研究探讨超声骨密度检测法对诊断早期儿童佝偻病的临床应用价值,以期为早期儿童佝偻病的诊断提供新的方法。方法：选择2015年1月~2016年12月来本院就诊的160例儿童佝偻病患者和在本院进行体检的健康儿童100例为研究对象。分别编入观察组(n=160)和对照组(n=100),对两组儿童行超声骨密度检测。统计比较骨密度对早期儿童的佝偻病的诊断正确率;其次,对观察组和对照组儿童骨密度值进行比较分析;再者,对两组儿童的血钙、碱性磷酸酶浓度进行比较。结果：(1) 通过与佝偻病诊断金标准骨骼X射线检查法相比,超声骨密度检查法有着较高的诊断正确率,且表现为年龄越小诊断准确率越高;(2) 在各个年龄段观察组患者骨密度Z值均显著低于对照组儿童(P<0.05),且年龄越低与对照组间差异越大,观察组患者不同性别间骨密度Z值无显著性差异(P>0.05);(3) 观察组患者的血钙浓度低于对照组,碱性磷酸酶浓度则高于对照组,在观察组内血钙浓度随着骨密度的增加而增加,碱性磷酸酶浓度随着骨密度增加而降低。结论：通过超声骨密度的检查能够及早的对儿童佝偻病进行确诊,且有着很高的诊断准确率,是一种有效的临床诊断儿童佝偻病的新方法,并加以推广应用。     

First place winner. Recurrent febrile seizures: an unusual presentation of nutritional rickets

Nutritional rickets is a serious disease that is infrequently encountered in the United States today because of the fortification of infant formulas and dairy products with vitamin D. We report a case of undiagnosed nutritional rickets presenting with recurrent febrile seizures. Febrile seizures, a common and usually benign presenting complaint, are not among the symptoms generally known to be associated with rickets. Therefore, the disease was uncovered only after a careful history and physical examination prompted a more thorough investigation into an underlying cause for recurrent seizures. The diagnosis was subsequently confirmed by quantitative laboratory testing. We review the historical and cultural factors, symptoms, and physical findings suggestive of this potentially serious yet easily treatable disease.     

Pruning the ricket thicket

Overexpression of FGF23 results in hypophosphatemic rickets, which is characterized by renal phosphate wasting, inappropriately low circulating levels of the active form of vitamin D, and skeletal abnormalities. The precise mechanisms of how excess FGF23 leads to hypophosphatemic rickets are not clear. In this issue of the JCI, Bai and colleagues demonstrate that deletion or inhibition of CYP24A1, which initiates degradation of the active form of vitamin D, ameliorates skeletal abnormalities in two mouse models of hypophosphatemic rickets. While this work supports an important role for excess CYP24A1 activity in the pathogenesis of FGF23-mediated hypophosphatemic rickets, more work will need to be done before CYP24A1 inhibition can be integrated into the management of patients living with these diseases.     

EXPERIMENTAL RICKETS IN RATS : V. THE EFFECT OF VARYING THE ORGANIC CONSTITUENTS OF A RICKETS-PRODUCING DIET.

1. Casein phosphorus does not completely prevent the development of rickets when substituted in Diet 84 in amount equivalent to a protective dose of basic potassium phosphate. 2. The protection given by lecithin is equivalent to its phosphorus content. 3. The protection given by yeast is at least proportional to its phosphorus content. An amount carrying sufficient vitamine B to promote growth, but insufficient to provide adequate phosphorus, does not prevent rickets. 4. Vitamine A, in the form of butter or butter fat to the amount of 10 per cent of the diet, neither prevents nor cures rickets. 5. The substitution of 10 per cent of egg albumin in Diet 84 improves the nutrition, but does not prevent rickets. 6. The addition of meat to Diet 84, thereby supplying an abundance of phosphorus, promotes normal growth and normal bone formation. A diet consisting solely of meat and flour is inadequate for proper growth, and leads to changes in the bones comparable with those observed on a diet low in calcium, but rich in phosphorus. 7. A diet has been found which contains the necessary food elements for approximately normal growth, and in which the only known deficiency is phosphorus. This leads regularly to the production of rickets.