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Rickets
Kinds of Rickets Selected AbstractsRickets and osteomalacia in northeast Iran: report of 797 casesINTERNATIONAL JOURNAL OF RHEUMATIC DISEASES, Issue 2 2008Mohammadhassan JOKAR ABSTRACT Aim:, To study the clinical, biochemical and radiographic features of rickets and osteomalacia in north-east of Iran. Methods:, We retrospectively reviewed the medical records of all patients with diagnosis of rickets and osteomalacia during the past 20 years (1986,2006) in the rheumatology outpatient clinic of Imam Reza Hospital, Mashhad, Iran. Results:, There were 797 patients (795 female, 2 male). Their ages were between 8,74 years. Most cases were in their second decade of life. The most common clinical findings were: bone pain 96.4%, muscle weakness 81%, abnormal gait 43%, and bone deformity 19.6%. The most common laboratory finding was high serum alkaline phosphatase (92%) followed by hypophosphatemia 54.6%, and hypocalcemia (21%). Radiographic findings were: epiphyseal growth plate alterations 74.4%, osteopenia 63%, ground glass appearance 28.6%, and Looser's zones 26.5%. All except four patients were cured with vitamin D and calcium. Conclusion:, Rickets and osteomalacia are common disorders in our region. Females especially in the growing years are often involved. The most common cause of rickets and osteomalacia in our region is vitamin D deficiency probably due to inadequate sun exposure. [source] Compound Heterozygous Mutations in the Vitamin D Receptor in a Patient With Hereditary 1,25-Dihydroxyvitamin D-Resistant Rickets With Alopecia,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 4 2009Yulin Zhou Abstract Hereditary vitamin D-resistant rickets (HVDRR) is a rare recessive genetic disorder caused by mutations in the vitamin D receptor (VDR). In this study, we examined the VDR in a young girl with clinical features of HVDRR including rickets, hypophosphatemia, and elevated serum 1,25(OH)2D. The girl also had total alopecia. Two mutations were found in the VDR gene: a nonsense mutation (R30X) in the DNA-binding domain and a unique 3-bp in-frame deletion in exon 6 that deleted the codon for lysine at amino acid 246 (,K246). The child and her mother were both heterozygous for the 3-bp deletion, whereas the child and her father were both heterozygous for the R30X mutation. Fibroblasts from the patient were unresponsive to 1,25(OH)2D3 as shown by their failure to induce CYP24A1 gene expression, a marker of 1,25(OH)2D3 responsiveness. [3H]1,25(OH)2D3 binding and immunoblot analysis showed that the patient's cells expressed the VDR,K246 mutant protein; however, the amount of VDR,K246 mutant protein was significantly reduced compared with wildtype controls. In transactivation assays, the recreated VDR,K246 mutant was unresponsive to 1,25(OH)2D3. The ,K246 mutation abolished heterodimerization of the mutant VDR with RXR, and binding to the coactivators DRIP205 and SRC-1. However, the ,K246 mutation did not affect the interaction of the mutant VDR with the corepressor Hairless (HR). In summary, we describe a patient with compound heterozygous mutations in the VDR that results in HVDRR with alopecia. The R30X mutation truncates the VDR, whereas the ,K246 mutation prevents heterodimerization with RXR and disrupts coactivator interactions. [source] Rickets in the 17th Century,,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 10 2006Jeffrey LH O'Riordan Abstract Rickets was first documented as a cause of death in the Bills of Mortality for The City of London in 1634, but detailed descriptions were only published between 1645 and 1668. It was thought at the time that this was a new disease in England, but there was no indication as to the cause of the condition. However, air pollution from smoke produced by burning coal caused serious problems at that time, and so it can be suggested that vitamin D deficiency was responsible. [source] Nutritional Rickets: An Old Disease ReturnsNUTRITION REVIEWS, Issue 4 2002Steven A. Abrams M.D. Nutritional rickets, an ancient disease that was thought to have been cured in the early part of the 20th century, has made an unexpected comeback in recent years throughout the world. Although the frequency of its occurrence is poorly documented, increasing case reports of rickets are apparently related to low dietary intake of vitamin D and calcium and decreased sunshine exposure. Greater awareness of this problem is needed, as are further data regarding vitamin D status and incidence of rickets among infants and toddlers. Routine provision of supplemental vitamin D to all breastfed infants remains controversial, but may become more widely recommended. [source] Epidermal Nevus Syndrome Associated with Adnexal Tumors, Spitz Nevus, and Hypophosphatemic Vitamin D-Resistant RicketsPEDIATRIC DERMATOLOGY, Issue 1 2005Érica Sanae Kishida M.D. We present a patient with epidermal nevus syndrome associated with hypophosphatemic vitamin D-resistant rickets and multiple adnexal and spindle cell tumors. [source] Endodontic Management Of A Patient With X-linked Hypophosphataemic RicketsAUSTRALIAN ENDODONTIC JOURNAL, Issue 2 2001ADEC, Drs S. Alexander BDS First page of article [source] Fibroblast growth factor 23 reduces expression of type IIa Na+/Pi co-transporter by signaling through a receptor functionally distinct from the known FGFRs in opossum kidney cellsGENES TO CELLS, Issue 5 2005Xiaomei Yan Fibroblast growth factor (FGF) 23 is an important phosphaturic factor that inhibits inorganic phosphate (Pi) reabsorption from the renal proximal tubule. Its overproduction and proteolysis-resistant mutation such as R179Q cause tumor-induced osteomalacia and autosomal dominant hypophosphatemic rickets, respectively. To clarify the signaling mechanisms of FGF23 that mediate the reduction of Pi reabsorption, we inhibited the function of the known FGFRs in opossum kidney (OK-E) cells by expressing a dominant-negative (DN) form of FGFR. OK-E cells, which represent the renal proximal tubular cells, expressed all four known FGFRs. FGF23(R179Q) bound to and activated FGFR2, a prominent FGFR expressed in OK-E cells. The activated receptor transmitted a signal to increase the expression of type IIa Na+/Pi co-transporter and the Pi uptake. Expression of FGFR2(DN), which suppresses the major FGFR-mediated signal through the FRS2,-ERK pathway, reversed the function of FGF23(R179Q). When FGF23(R179Q) was applied to the basolateral side of polarized OK-E cells, regardless of the FGFR2(DN) expression, the apical Pi uptake decreased significantly. The apical application of FGF23(R179Q) in the polarized cells did not show such decrease but increase. The exogenously expressed FGFR2 was detectable only at the apical membrane. These results suggest that an FGF23 receptor, which is functionally distinct from the known FGFRs, is expressed at the basolateral membrane of OK-E cells. [source] Residual rickets or osteomalacia: a case dating from the 16,18th centuries from Krosno Odrza,skie, PolandINTERNATIONAL JOURNAL OF OSTEOARCHAEOLOGY, Issue 5 2009E. Haduch Abstract A skeleton from a 16,18th century burial site in Krosno Odrza,skie, Poland, was examined using classical morphological, metric and macroscopic palaeopathological observations, as well as radiography and tomography of the skull and long bones. A wide variety of the observed bone deformations probably occurred as a consequence of past rickets and/or osteomalacia, whose primary cause may also have been chronic renal failure. Preservation of the bones enables a discussion of the cause of such pathological changes. The subject under study appears to be a very interesting example of an individual whose skeleton shows advanced pathological alterations associated with the subject's vitamin D deficiency, overall health conditions and relatively long lifespan. Copyright © 2008 John Wiley & Sons, Ltd. [source] Rickets and osteomalacia in northeast Iran: report of 797 casesINTERNATIONAL JOURNAL OF RHEUMATIC DISEASES, Issue 2 2008Mohammadhassan JOKAR ABSTRACT Aim:, To study the clinical, biochemical and radiographic features of rickets and osteomalacia in north-east of Iran. Methods:, We retrospectively reviewed the medical records of all patients with diagnosis of rickets and osteomalacia during the past 20 years (1986,2006) in the rheumatology outpatient clinic of Imam Reza Hospital, Mashhad, Iran. Results:, There were 797 patients (795 female, 2 male). Their ages were between 8,74 years. Most cases were in their second decade of life. The most common clinical findings were: bone pain 96.4%, muscle weakness 81%, abnormal gait 43%, and bone deformity 19.6%. The most common laboratory finding was high serum alkaline phosphatase (92%) followed by hypophosphatemia 54.6%, and hypocalcemia (21%). Radiographic findings were: epiphyseal growth plate alterations 74.4%, osteopenia 63%, ground glass appearance 28.6%, and Looser's zones 26.5%. All except four patients were cured with vitamin D and calcium. Conclusion:, Rickets and osteomalacia are common disorders in our region. Females especially in the growing years are often involved. The most common cause of rickets and osteomalacia in our region is vitamin D deficiency probably due to inadequate sun exposure. [source] Therapeutic Effects of Anti-FGF23 Antibodies in Hypophosphatemic Rickets/Osteomalacia,,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 11 2009Yukiko Aono Abstract X-linked hypophosphatemia (XLH), characterized by renal phosphate wasting, is the most common cause of vitamin D-resistant rickets. It has been postulated that some phosphaturic factor plays a causative role in XLH and its murine homolog, the Hyp mouse. Fibroblast growth factor 23 (FGF23) is a physiological phosphaturic factor; its circulatory level is known to be high in most patients with XLH and Hyp mice, suggesting its pathophysiological role in this disease. To test this hypothesis, we treated Hyp mice with anti-FGF23 antibodies to inhibit endogenous FGF23 action. A single injection of the antibodies corrected the hypophosphatemia and inappropriately normal serum 1,25-dihydroxyvitamin D. These effects were accompanied by increased expressions of type IIa sodium-phosphate cotransporter and 25-hydroxyvitamin-D-1,-hydroxylase and a suppressed expression of 24-hydroxylase in the kidney. Repeated injections during the growth period ameliorated the rachitic bone phenotypes typically observed in Hyp mice, such as impaired longitudinal elongation, defective mineralization, and abnormal cartilage development. Thus, these results indicate that excess actions of FGF23 underlie hypophosphatemic rickets in Hyp mice and suggest a novel therapeutic potential of the FGF23 antibodies for XLH. [source] Compound Heterozygous Mutations in the Vitamin D Receptor in a Patient With Hereditary 1,25-Dihydroxyvitamin D-Resistant Rickets With Alopecia,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 4 2009Yulin Zhou Abstract Hereditary vitamin D-resistant rickets (HVDRR) is a rare recessive genetic disorder caused by mutations in the vitamin D receptor (VDR). In this study, we examined the VDR in a young girl with clinical features of HVDRR including rickets, hypophosphatemia, and elevated serum 1,25(OH)2D. The girl also had total alopecia. Two mutations were found in the VDR gene: a nonsense mutation (R30X) in the DNA-binding domain and a unique 3-bp in-frame deletion in exon 6 that deleted the codon for lysine at amino acid 246 (,K246). The child and her mother were both heterozygous for the 3-bp deletion, whereas the child and her father were both heterozygous for the R30X mutation. Fibroblasts from the patient were unresponsive to 1,25(OH)2D3 as shown by their failure to induce CYP24A1 gene expression, a marker of 1,25(OH)2D3 responsiveness. [3H]1,25(OH)2D3 binding and immunoblot analysis showed that the patient's cells expressed the VDR,K246 mutant protein; however, the amount of VDR,K246 mutant protein was significantly reduced compared with wildtype controls. In transactivation assays, the recreated VDR,K246 mutant was unresponsive to 1,25(OH)2D3. The ,K246 mutation abolished heterodimerization of the mutant VDR with RXR, and binding to the coactivators DRIP205 and SRC-1. However, the ,K246 mutation did not affect the interaction of the mutant VDR with the corepressor Hairless (HR). In summary, we describe a patient with compound heterozygous mutations in the VDR that results in HVDRR with alopecia. The R30X mutation truncates the VDR, whereas the ,K246 mutation prevents heterodimerization with RXR and disrupts coactivator interactions. [source] Enzyme Replacement Therapy for Murine Hypophosphatasia,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 6 2008José Luis Millán PhD Abstract Introduction: Hypophosphatasia (HPP) is the inborn error of metabolism that features rickets or osteomalacia caused by loss-of-function mutation(s) within the gene that encodes the tissue-nonspecific isozyme of alkaline phosphatase (TNALP). Consequently, natural substrates for this ectoenzyme accumulate extracellulary including inorganic pyrophosphate (PPi), an inhibitor of mineralization, and pyridoxal 5,-phosphate (PLP), a co-factor form of vitamin B6. Babies with the infantile form of HPP often die with severe rickets and sometimes hypercalcemia and vitamin B6 -dependent seizures. There is no established medical treatment. Materials and Methods: Human TNALP was bioengineered with the C terminus extended by the Fc region of human IgG for one-step purification and a deca-aspartate sequence (D10) for targeting to mineralizing tissue (sALP-FcD10). TNALP-null mice (Akp2,/,), an excellent model for infantile HPP, were treated from birth using sALP-FcD10. Short-term and long-term efficacy studies consisted of once daily subcutaneous injections of 1, 2, or 8.2 mg/kg sALP-FcD10 for 15, 19, and 15 or 52 days, respectively. We assessed survival and growth rates, circulating levels of sALP-FcD10 activity, calcium, PPi, and pyridoxal, as well as skeletal and dental manifestations using radiography, ,CT, and histomorphometry. Results:Akp2,/, mice receiving high-dose sALP-FcD10 grew normally and appeared well without skeletal or dental disease or epilepsy. Plasma calcium, PPi, and pyridoxal concentrations remained in their normal ranges. We found no evidence of significant skeletal or dental disease. Conclusions: Enzyme replacement using a bone-targeted, recombinant form of human TNALP prevents infantile HPP in Akp2,/, mice. [source] FGF-23 Is a Potent Regulator of Vitamin D Metabolism and Phosphate Homeostasis,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 3 2004Takashi Shimada Abstract We analyzed the effects of an FGF-23 injection in vivo. FGF-23 caused a reduction in serum 1,25-dihydroxyvitamin D by altering the expressions of key enzymes for the vitamin D metabolism followed by hypophosphatemia. This study indicates that FGF-23 is a potent regulator of the vitamin D and phosphate metabolism. Introduction: The pathophysiological contribution of FGF-23 in hypophosphatemic diseases was supported by animal studies in which the long-term administration of recombinant fibroblast growth factor-23 reproduced hypophosphatemic rickets with a low serum 1,25-dihydroxyvitamin D [1,25(OH)2D] level. However, there is no clear understanding of how FGF-23 causes these changes. Materials and Methods: To elucidate the molecular mechanisms of the FGF-23 function, we investigated the short-term effects of a single administration of recombinant FGF-23 in normal and parathyroidectmized animals. Results: An injection of recombinant FGF-23 caused a reduction in serum phosphate and 1,25(OH)2D levels. A decrease in serum phosphate was first observed 9 h after the injection and was accompanied with a reduction in renal mRNA and protein levels for the type IIa sodium-phosphate cotransporter (NaPi-2a). There was no increase in the parathyroid hormone (PTH) level throughout the experiment, and hypophosphatemia was reproduced by FGF-23 in parathyroidectomized rats. Before this hypophosphatemic effect, the serum 1,25(OH)2D level had already descended at 3 h and reached the nadir 9 h after the administration. FGF-23 reduced renal mRNA for 25-hydroxyvitamin D-1,-hydroxylase and increased that for 25-hydroxyvitamin D-24-hydroxylase starting at 1 h. In addition, an injection of calcitriol into normal mice increased the serum FGF-23 level within 4 h. Conclusions: FGF-23 regulates NaPi-2a independently of PTH and the serum 1,25(OH)2D level by controlling renal expressions of key enzymes of the vitamin D metabolism. In conclusion, FGF-23 is a potent regulator of phosphate and vitamin D homeostasis. [source] Tryptophan Missense Mutation in the Ligand-Binding Domain of the Vitamin D Receptor Causes Severe Resistance to 1,25-Dihydroxyvitamin D,,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 9 2002T. M. Nguyen Ph.D. Abstract In this study, two related young children, brother and sister, exhibited severe vitamin D-resistant rickets without alopecia. Sequence analysis of the total vitamin D receptor (VDR) cDNA from skin fibroblasts revealed a substitution of the unique tryptophan of the VDR by arginine at amino acid 286 (W286R). Cultured skin fibroblasts of the two patients expressed normal-size VDR protein (immunocytochemistry and Western blotting) and normal length VDR mRNA (Northern blotting). But, these fibroblasts, as well as COS-7 cells transfected with the W286R mutant, failed to bind 3H 1,25-dihydroxyvitamin D3 [1,25(OH)2D3]. The tryptophan substitution did not affect VDR trafficking toward the nucleus but abolished the 24-hydroxylase gene response to 1,25(OH)2D3, even at 10,6 M concentrations. In conclusion, this case report of a new family with hereditary vitamin D- resistant rickets (HVDRR) emphasizes the crucial role of the VDR tryptophan for ligand binding and for transactivation of 1,25(OH)2D3 target genes. It clearly shows the clinical significance of this VDR amino acid for calcium homeostasis and bone mineralization. This observation suggests further that the presence of a stable VDR-bound ligand may not be obligatory for normal hair follicle development. [source] Craniofacial morphology in patients with hypophosphataemic vitamin-D-resistant rickets: a cephalometric studyJOURNAL OF ORAL REHABILITATION, Issue 7 2009S. H. AL-JUNDI Summary, Hypophosphataemic vitamin-D-resistant rickets (HVDRR) is a hereditary disease mainly transmitted as an X-linked dominant trait and characterized by certain general clinical signs (Filho HM, de Castro LC, Damiani D. Arq Bras Endocrinol Metab. 2006;50:802). In literature, only one study had been published in 1965 on the cephalometric findings in patients with HVDRR (Marks SC, Lindahl RL, Bawden JW. J Dent Child. 1965;32:259). This is the first detailed study on craniofacial characteristics of patients with HVDRR in the dental literature. The aim of this study was to determine the effect of HVDRR on the parameters of the craniofacial skeleton of young Jordanian patients using cephalometric analysis. Lateral cephalometric radiographs were made for 22 Jordanian children (aged 2,16 years) diagnosed with HVDRR. The cephalometeric parameters of HVDRR group were compared with those of normal control group matched for gender and chronological age using paired t -test. The HVDRR group had a significant increase in the SNBa angle (P < 0·01); as well as reduced anterior cranial base length (P = 0·01), reduced maxillary length, corpus mandibular length and mandibular height (P = 0·01, 0·04 and 0·008 respectively). The cranial base and gonial angles were significantly increased in diseased individual, but the SNA and ANB angles were significantly reduced (P = 0·018 and 0·000 respectively). The angulation of the lower incisor to mandibular plane was also significantly reduced in the diseased group compared with Jordanian norm (P = 0·004). Patients with HVDRR have deficiency in the anterior cranial base length, ramus height and cranial base angle. Patients with HVDRR also have class III skeletal relationship. [source] Modern India and the vitamin D dilemma: Evidence for the need of a national food fortification programMOLECULAR NUTRITION & FOOD RESEARCH (FORMERLY NAHRUNG/FOOD), Issue 8 2010Uma S. Babu Abstract India is located between 8.4 and 37.6°N latitude with the majority of its population living in regions experiencing ample sunlight throughout the year. Historically, Indians obtained most of their vitamin D through adequate sun exposure; however, darker skin pigmentation and the changes which have accompanied India's modernization, including increased hours spent working indoors and pollution, limit sun exposure for many. Inadequate sun exposure results in reduced vitamin D synthesis and ultimately poor vitamin D status if not compensated by dietary intake. Dietary vitamin D intake is very low in India because of low consumption of vitamin D rich foods, absence of fortification and low use of supplements. All these factors contribute to poor vitamin D status as measured by low circulating levels of 25-hydroxy vitamin D. Our review searches the published literature specific to India for evidence that would confirm the need to fortify food staples with vitamin D or stimulate public health policies for vitamin D supplementation and dietary guidelines tailored to the Indian diet. This review documents findings of widespread vitamin D deficiency in Indian populations in higher and lower socioeconomic strata, in all age groups, in both genders and people in various professions. Moreover, poor vitamin D status in India is accompanied by increased bone disorders including osteoporosis, osteomalacia in adults and rickets and other bone deformities in children. Without a concerted national effort to screen for vitamin D status, to implement policies or guidelines for vitamin D fortification and/or supplementation and to re-assess recommended dietary intake guidelines, dramatic increase in the number of bone disorders and other diseases may lie ahead. [source] Hereditary hypophosphatemias: New genes in the bone,kidney axis (Review Article)NEPHROLOGY, Issue 4 2007ARMANDO L NEGRI SUMMARY: Hypophosphatemia due to isolated renal phosphate wasting is a genetically heterogeneous disease. Two new genes linked to two different forms of hereditary hypophosphatemias have recently been described. Autosomal recessive form of hypophosphatemic rickets was mapped to chromosome 4q21 and identified homozygous mutations in dentin matrix protein 1 (DMP1) gene, which encodes a non-collagenous bone matrix protein. Intact plasma levels of the phosphaturic protein FGF23 (fibroblast growth factor 23) were clearly elevated in some of the affected individuals, providing a possible explanation for the phosphaturia and inappropriately normal 1,25(OH)2D levels, and suggesting that DMP1 may regulate FGF23 expression. Hereditary hypophosphatemic rickets with hypercalciuria is another rare disorder of autosomal recessive inheritance. Affected individuals present with hypercalciuria due to increased serum 1,25-dihydroxyvitamin D levels and increased intestinal calcium absorption. The disease was mapped to a 1.6 Mbp region on chromosome 9q34, which contains SLC34A3, the gene encoding the renal sodium-phosphate cotransporter NaPi-IIc. This was the first demonstration that NaPi-IIc has a key role in the regulation of phosphate homeostasis. Thus, DMP1 and NaPi-IIc add two new members to the bone,kidney axis proposed since it was discovered that the first phosphatonin, FGF23, was of osteoblastic/osteocyte origin. This provides a mechanism for the skeleton to communicate with the kidney to coordinate the mineralization of extracelular matrix and the renal handling of phosphate. [source] Vitamin D requirement and setting recommendation levels: long-term perspectivesNUTRITION REVIEWS, Issue 2008Leif Mosekilde Target intakes of vitamin D to prevent rickets and osteomalacia are difficult to estimate because of the dual sources of vitamin D with dermal production and absorption from the intestine. However, vitamin D deficiency is associated with other diseases, e.g., myopathy, falls, fractures, autoimmune disorders, cardiovascular diseases, and malignancies, which underlines the necessity of redefining recommendations. A plasma level of 25-hydroxyvitamin D (25OHD) <50 nmol/L increases the risk of secondary hyperparathyroidism, whereas levels between 75 and 100 nmol/L appear optimal for maintaining general health. In adults, a minimum dietary intake of 17.5,25 µg/day is necessary to achieve these levels. Perspectives of future research are outlined here. [source] Nutritional Rickets: An Old Disease ReturnsNUTRITION REVIEWS, Issue 4 2002Steven A. Abrams M.D. Nutritional rickets, an ancient disease that was thought to have been cured in the early part of the 20th century, has made an unexpected comeback in recent years throughout the world. Although the frequency of its occurrence is poorly documented, increasing case reports of rickets are apparently related to low dietary intake of vitamin D and calcium and decreased sunshine exposure. Greater awareness of this problem is needed, as are further data regarding vitamin D status and incidence of rickets among infants and toddlers. Routine provision of supplemental vitamin D to all breastfed infants remains controversial, but may become more widely recommended. [source] The vitamin D slant on allergyPEDIATRIC ALLERGY AND IMMUNOLOGY, Issue 7 2006Matthias Wjst Oral vitamin D supplementation has been introduced into modern medicine to prevent rickets without the knowledge that this may have profound immunological consequences. The main vitamin D metabolite calcitriol suppresses dendritic cell maturation and consecutive Th1 cell development, which has independently described as a key mechanism of allergy development. Animal studies and epidemiological surveys now provide a first link of early vitamin D supplementation and later allergy where several vitamin D regulated genes seem to be involved. A randomized clinical trial of vitamin D supplementation could be a further step to follow up the vitamin hypothesis. [source] Epidermal Nevus Syndrome Associated with Adnexal Tumors, Spitz Nevus, and Hypophosphatemic Vitamin D-Resistant RicketsPEDIATRIC DERMATOLOGY, Issue 1 2005Érica Sanae Kishida M.D. We present a patient with epidermal nevus syndrome associated with hypophosphatemic vitamin D-resistant rickets and multiple adnexal and spindle cell tumors. [source] Hepatic osteodystrophy in chronic cholestasis: Evidence for a multifactorial etiologyPEDIATRIC TRANSPLANTATION, Issue 2 2002Gordon L. Klein Abstract: Children with cholestatic liver disease have been thought to develop hepatic osteodystrophy resulting from vitamin D and calcium malabsorption, resulting in secondary hyperparathyroidism and osteomalacia or rickets. However, treatment with vitamin D has not always proven successful in improving the bone disturbance. The aim of our study was to determine the role of vitamin D deficiency in the pathogenesis of hepatic osteodystrophy. We studied five patients, three female and two male, ages 0.9,19 yr, with biopsy-proven chronic cholestatic liver disease and previously low serum levels of vitamin D despite oral intake of vitamin D preparations. Patients were admitted to the Clinical Research Center for 8 days for sunlight deprivation and ultraviolet light substitution and for determinations of serum 25-hyroxyvitamin D(25(OH)) D2 and -D3, osteocalcin, and type I collagen telopeptide (ICTP), the last two being markers of bone formation and resorption, respectively. Samples were taken on admission, at discharge, and 1 month later. Results demonstrated low serum levels of osteocalcin and normal circulating levels of ICTP. Admission serum 25(OH)D2 levels were uniformly low or undetectable and remained so. Admission levels of circulating 25(OH)D3 were normal or low and did not rise during ultraviolet light therapy or subsequent resumption of oral vitamin D therapy and remained low 1 month later. These results indicate that in the face of low,normal to low total 25(OH)D levels, the low osteocalcin and normal ICTP levels suggest that decreased bone formation and not increased bone resorption is the main determinant of bone loss in a subset of children with chronic cholestatic liver disease. [source] Prevalence and risk factors of vitamin D deficiency rickets in Hokkaido, JapanPEDIATRICS INTERNATIONAL, Issue 4 2009Kumihiro Matsuo Abstract Background:, Resurgence of vitamin D deficiency rickets has been recognized worldwide. While many cases of this disease have been reported in Hokkaido, the northern island of Japan, no prevalence data is available. Here, we investigated the prevalence and risk factors of vitamin D deficiency rickets in Hokkaido. Methods:, A specially designed questionnaire was sent to 84 major pediatric departments of hospitals in Hokkaido to collect information of the confirmed cases between July 1999 and June 2004. Results:, Sixty-seven hospitals responded to the questionnaire. Of these, 20 hospitals reported 31 confirmed cases. All the patients were infants and toddlers, less than 4 years of age. The prevalence of cases in a recent year was estimated to be nine in 100 000 children under four years of age. Most of the 31 cases in our study were breast-fed. Eleven cases showed signs of malnutrition due to unbalanced diet or dietary restriction. Furthermore, the prevalence of cases was higher in the northeastern region than in the southwestern region. The number of cases increased gradually from the end of winter to spring. Conclusions:, This is the first report ascertaining the prevalence of vitamin D deficiency rickets in Hokkaido, Japan. Limited exposure to sunlight and inadequate diet in early childhood are key risk factors of this disease. Thus, it is crucial to introduce active recommendations for vitamin D supplementation based on age, residential area, and to advocate public awareness for preventing this disease. [source] Nutritional rickets and z scores for height in the United Arab Emirates: To D or not to D?PEDIATRICS INTERNATIONAL, Issue 4 2008Jaishen Rajah Abstract Background: Vitamin D deficiency is still prevalent worldwide, including the Middle East. A cohort of patients with nutritional rickets was treated with vitamin D2 (ergocalciferol) alone. After this intervention, patients were followed to document changes in z scores for height after treatment. The secondary aim was to determine the proportion of affected children who had vitamin D deficiency or calcium deficiency. Methods: Z score for height was calculated as the difference between the observed value and the median value, divided by the SD of the population. Z scores were compared in patients before and after treatment. Results: The improvement in z score after treatment was 0.86 ± 0.95. The 95% confidence interval for the mean difference was 1.32,0.40 (t = 3.95, P < 0.001). With a diagnostic cut-off for 25 hydroxyvitamin D3 (25D) deficiency of <25 nmol/L, only half were diagnosed with severe vitamin D deficiency. The remaining patients had presumable calcium deficiency. The alkaline phosphatase (ALP) was negatively correlated to z scores, implying that higher ALP concentrations predicted severe bone disease (lower z scores). The variables 25D and age were moderately and positively correlated (Pearson's r = 0.59, 95%CI: 0.15,0.84; P = 0.01), indicating that younger infants had the lowest 25D levels. Conclusion: Vitamin D alone was efficient in resolving radiological and biochemical disturbances as well as improving z scores for height in a cohort of children with nutritional rickets, which included patients with 25D deficiency as well as calcium deficiency. The results support the hypothesis of the interplay and continuum of 25D deficiency and calcium deficiency in the pathogenesis of rickets. [source] Ligand-independent Regulation of the hairless Promoter by Vitamin D Receptor,PHOTOCHEMISTRY & PHOTOBIOLOGY, Issue 2 2008Andrew Engelhard The characteristic alopecia associated with mutations in the hairless (hr) and vitamin D receptor (VDR) genes defines the resulting genetic disorders, known as atrichia and VDRRIIa rickets, as phenocopies. In both cases, the separation of the dermal papilla from the regressing hair follicle at the onset of the first catagen phase of the hair cycle and the development of dermal cysts and utricules subsequent to mutation of either gene suggests that their activities affect the same regulatory pathways. VDR functions as a hormonally activated transcription factor, and a role in transcription has been postulated for Hr due in part to its nuclear localization and homology with the GATA-1 zinc-finger domain. Therefore, we examined the hypothesis that VDR and Hr have a direct regulatory effect on each other via a transcriptional mechanism. Ectopic expression of the VDR repressed hr promoter activity in HaCaT cells and primary human keratinocytes (PHKs). While this repression occurs in the absence of 1,25 dihydroxyvitamin D3 (D3), the addition of ligand greatly augments the effect. However, we also demonstrate the rare phenomenon of ligand-independent promoter transactivation by VDR. We show that the full-length promoter is transactivated by VDR in a ligand-independent and cell type-specific manner, suggesting that direct transcriptional regulation of hr by the VDR accounts in part for the phenotypic overlap between atrichia and VDRRIIa rickets. [source] Life and death in a civitas capital: Metabolic disease and trauma in the children from late Roman Dorchester, DorsetAMERICAN JOURNAL OF PHYSICAL ANTHROPOLOGY, Issue 3 2010Mary E. Lewis Abstract The impact that "Romanization" and the development of urban centers had on the health of the Romano-British population is little understood. A re-examination of the skeletal remains of 364 nonadults from the civitas capital at Roman Dorchester (Durnovaria) in Dorset was carried out to measure the health of the children living in this small urban area. The cemetery population was divided into two groups; the first buried their dead organized within an east,west alignment with possible Christian-style graves, and the second with more varied "pagan" graves, aligned north,south. A higher prevalence of malnutrition and trauma was evident in the children from Dorchester than in any other published Romano-British group, with levels similar to those seen in postmedieval industrial communities. Cribra orbitalia was present in 38.5% of the children, with rickets and/or scurvy at 11.2%. Twelve children displayed fractures of the ribs, with 50% of cases associated with rickets and/or scurvy, suggesting that rib fractures should be considered during the diagnosis of these conditions. The high prevalence of anemia, rickets, and scurvy in the Poundbury children, and especially the infants, indicates that this community may have adopted child-rearing practices that involved fasting the newborn, a poor quality weaning diet, and swaddling, leading to general malnutrition and inadequate exposure to sunlight. The Pagan group showed no evidence of scurvy or rib fractures, indicating difference in religious and child-rearing practices but that both burial groups were equally susceptible to rickets and anemia suggests a shared poor standard of living in this urban environment. Am J Phys Anthropol, 2010. © 2009 Wiley-Liss, Inc. [source] Diagnosis and management of unusual dental abscesses in childrenAUSTRALIAN DENTAL JOURNAL, Issue 3 2003WK Seow Abstract Although the majority of dental abscesses in children originate from dental caries or trauma, a few are associated with unusual conditions which challenge diagnosis and management. Recent research findings have shed light on these unusual entities and greatly improved understanding of their clinical implications. These conditions include developmental abnormalities such as dens invaginatus in which there is an invagination of dental tissues into the pulp chamber and dens evaginatus in which a tubercle containing pulp is found on the external surface of a tooth crown. In addition, inherited conditions which show abnormal dentine such as dentine dysplasia, dentinogenesis imperfecta, and osteogenesis imperfecta predispose the dentition to abscess formation. Furthermore, ,spontaneous' dental abscesses are frequently encountered in familial hypophosphataemia, also known as vitamin D-resistant rickets, in which there is hypomineralization of dentine and enlargement of the pulp. In addition to developmental conditions, there are also acquired conditions which may cause unusual dental abscesses. These include pre-eruptive intracoronal resorption which was previously known as ,pre-eruptive caries' or the ,fluoride bomb'. In addition, some undiagnosed infections associated with developing teeth are now thought to be the mandibular infected buccal cysts which originate from infection of the developing dental follicles. In the present paper, these relatively unknown entities which cause unusual abscesses in children are reviewed with the aim of updating the general practitioner in their diagnosis and management. [source] Vitamin D discovery outpaces FDA decision makingBIOESSAYS, Issue 2 2008Trevor G. Marshall The US FDA currently encourages the addition of vitamin D to milk and cereals, with the aim of reducing rickets in children and osteoporosis in adults. However, vitamin D not only regulates the expression of genes associated with calcium homeostasis, but also genes associated with cancers, autoimmune disease, and infection. It does this by controlling the activation of the vitamin D receptor (VDR), a type 1 nuclear receptor and DNA transcription factor. Molecular biology is rapidly coming to an understanding of the multiplicity of roles played by the VDR, but clinical medicine is having difficulty keeping up with the pace of change. For example, the FDA recently proposed a rule change that will encourage high levels of vitamin D to be added to even more foods, so that the manufacturers can claim those foods "reduce the risk of osteoporosis". The FDA docket does not review one single paper detailing the transcriptional activity of vitamin D, even though, on average, one new paper a day is being published on that topic. Nor do they review whether widespread supplementation with vitamin D, an immunomodulatory secosteroid, might predispose the population to immune dysfunction. This BioEssay explores how lifelong supplementation of the food chain with vitamin D might well be contributing to the current epidemics of obesity and chronic disease. BioEssays 30:173,182, 2008. © 2008 Wiley Periodicals, Inc. [source] A novel mutation in the VDR gene in hereditary vitamin D-resistant ricketsBRITISH JOURNAL OF DERMATOLOGY, Issue 1 2008K. Arita First page of article [source] Photocaged Agonist for an Analogue-Specific form of the Vitamin D ReceptorCHEMBIOCHEM, Issue 7 2007John B. Biggins Dr. Abstract Nuclear hormone receptors (NHRs) represent a diverse class of ligand-dependent transcriptional regulators. NHRs that have been rendered functionally inactive due to mutations that abrogate proper ligand binding can often be rescued by appropriately designed hormone analogues. The analogue-specific receptor,ligand pairs provide an ideal platform from which to develop new chemogenomic tools for the spatial and temporal control of gene expression. Here, we describe the synthesis and in vitro assessment of a photocaged VDR agonist specific to a mutant NHR that is associated with vitamin D-resistant rickets. The results provide insight into the utility of the agonist as a potential tool for photoinduced gene patterning. [source] | ||||||||||||||||||||||||||||