Development Of Rickets Research Articles

Impaired Growth Plate Maturation in XLH Is due to Both Excess FGF23 and Decreased 1,25-Dihydroxyvitamin D Signaling.

X-linked hypophosphatemia (XLH) is the most common form of hereditary hypophosphatemic rickets. The genetic basis for XLH is loss of function mutations in the phosphate-regulating endopeptidase X-linked (PHEX), which leads to increased circulating fibroblast growth factor 23 (FGF23). This increase in FGF23 impairs activation of vitamin D and attenuates renal phosphate reabsorption, leading to rickets. Previous studies have demonstrated that ablating FGF23 in the Hyp mouse model of XLH leads to hyperphosphatemia, high levels of 1,25-dihydroxyvitamin D, and is not associated with the development of rickets. Studies were undertaken to define a role for the increase in 1,25-dihydroxyvitamin D levels in the prevention of rickets in Hyp mice lacking FGF23. These mice were mated to mice lacking Cyp27b1, the enzyme responsible for activating vitamin D metabolites, to generate Hyp mice lacking both FGF23 and 1,25-dihydroxyvitamin D (FCH mice). Mice were fed a special diet to maintain normal mineral ion homeostasis. Despite normal mineral ions, Hyp mice lacking both FGF23 and Cyp27b1 developed rickets, characterized by an interrupted, expanded hypertrophic chondrocyte layer and impaired hypertrophic chondrocyte apoptosis. This phenotype was prevented when mice were treated with 1,25-dihydroxyvitamin D from day 2 until sacrifice on day 30. Interestingly, mice lacking FGF23 and Cyp27b1 without the PHEX mutation did not exhibit rickets. These findings define an essential PHEX-dependent, FGF23-independent role for 1,25-dihydroxyvitamin D in XLH and have important therapeutic implications for the treatment of this genetic disorder.

The genetic and epigenetic contributions to the development of nutritional rickets.

Nutritional rickets is an important disease in global health. Although nutritional rickets commonly manifests as bony deformities, there is an increased risk of life-threatening seizures secondary to hypocalcaemia. Dietary vitamin D deficiency is associated with the development of nutritional rickets among children and infants. This is especially true in populations of darker skinned individuals in high-latitude environments due to decreased ultraviolet light exposure, and in populations in tropical and subtropical climates due to cultural practices. A growing body of evidence has demonstrated that genetic factors might influence the likelihood of developing nutritional rickets by influencing an individual's susceptibility to develop deficiencies in vitamin D and/or calcium. This evidence has been drawn from a variety of different techniques ranging from traditional twin studies to next generation sequencing techniques. Additionally, the role of the epigenome in the development of rickets, although poorly understood, may be related to the effects of DNA methylation and non-coding RNAs on genes involved in bone metabolism. This review aims to provide an overview of the current evidence that investigates the genetic and epigenetic determinants of nutritional rickets.

50 Years Ago in TheJournalofPediatrics: Rickets and Antiepileptic Drugs: What Have We Learned?

Borgstedt AD, Bryson MF, Young LW, Forbes GB. Long-term administration of antiepileptic drugs and the development of rickets. J Pediatr 1972;81:9-15. In 1972, Borgstedt et al reported 2 neurologically impaired children who developed rickets after years of antiepileptic drug therapy. The diagnosis was based on physical findings, radiographs, and serum calcium, phosphate, and alkaline phosphatase levels. Rickets resolved with daily doses of calcium and large amounts of vitamin D, despite continuance of the antiepileptic drugs. Missing were measures of vitamin D metabolites, presumably owing to a lack of available clinical assays at that time. Our knowledge of vitamin D metabolism has progressed far beyond the already established metabolic pathways of hepatic 25-hydroxylation and renal 1-hydroxylation of that era. As the authors suspected, antiepileptic drugs, and other drugs, cause rickets by increased hepatic vitamin D catabolism. Induction of catabolic enzymes leaves less vitamin D for eventual renal conversion to the active metabolite 1,25 dihydroxyvitamin D (1,25-D). With inadequate 1,25-D, calcium absorption is impaired, contributing to inadequate bone mineralization. As extracellular calcium decreases, parathyroid hormone responds, but this response causes phosphaturia, further under mineralizing bone. In vitamin D disorders, bone chondrocyte function is also altered, leading to metaphyseal abnormalities explaining many hallmark features of vitamin D rickets, such as widened wrists and rachitic rosary. Other bone health issues in children with epileptic disorders, not related to vitamin D deficiency, include seizure-associated trauma, nonambulatory status, and nutritional deficiencies. The measurement of the main circulating metabolite, 25-hydroxyvitamin D (25-D), is widely available. Problems remain, including assay variability and an inconsistent relationship of level to clinical impact; for example, a 25-D level of 12 ng/mL may cause rickets in 1 individual and no notable signs in another. The 25-D levels are, at best, a surrogate for potential 1,25-D production. Another issue is that 25-D is measured in nanograms per milliliter, with acceptable levels in children generally considered to be more than 20 ng/mL. However, 1,25-D is measured in picograms per milliliter, or a 1000-fold less concentration. Why is a 25-D level of 10 000 pg/mL (=10 ng/mL) not enough substrate to provide adequate 1,25-D production to the 20-80 pg/mL reference range? From their inference of vitamin D deficiency, Borgstedt et al helped to identify an important preventable complication of antiepileptic drug use in children. Incorporating these findings into clinical guidelines remains to be completed.

Лечение и профилактика недостаточности и дефицита витамина D у детей и подростков

В статье приведены данные о метаболизме витамина D. Рассматриваются причины и клиническая картина его дефицита, роль последнего в развитии рахита, остеопороза, ряда заболеваний детского возраста. Приведены данные методических рекомендаций по лечению и профилактике дефицита витамина D у населения стран Центральной Европы относительно рекомендованных доз препаратов витамина D.

Ovarian effects of vitamin D: a systematic review

The history of the discovery of vitamin D (VD) has crossed 100 years. Initially, VD deficiency was limitedly associated with the development of rickets in children. Later, on the basis of a number of studies, it was found that VD deficiency is a risk factor for osteoporosis in men and women. However, the traditional concept of VD as the main regulator of calcium-phosphorus metabolism has undergone dramatic changes over the past two decades. A prerequisite for revising the role of VD and the spectrum of its biological properties was the identification of the distribution of its specific receptors in the body. VD receptors are expressed in the intestine, thyroid and parathyroid glands, kidneys, ovaries, uterus, placenta, hypothalamus, pituitary gland and play a vital function not only in calcium homeostasis. Accordingly, the list of target organs for VD action has been modified. VD deficiency, calculated on a pandemic scale, is a factor that increases the risk of developing not only osteoporosis, but also a number of other diseases. Observational and epidemiological studies have shown that reproductive system disorders are very often combined with VD insufficiency / deficiency. Subsequent scientific research aimed at establishing the role of VD in the formation of a particular pathology of the reproductive system has shown very ambiguous results. VD is recognized as an essential component of maintaining a woman’s reproductive health. Of course, the presence of an established association is not evidence of a causal relationship. There is a need for additional testing. This review focuses on the effect of VD on ovarian function and the formation of various dysfunctional conditions.

Rickets of our time: modern diagnosis and treatment

Rickets is a disease that has been known to mankind for several decades. Overcoming this public health problem was a triumph of science and public policy in the 20th century, but over the course of several decades rickets sharply returned as a result of cultural, environmental and political factors. Vitamin D plays a fundamental role in the regulation of calcium and phosphorus homeostasis, and, consequently, in the development of rickets. In addition to these classic skeletal effects, recent studies have shown that vitamin D has other significant extracellular effects that can complicate the course of the disease and have long-term effects on children’s health. Vitamin D sufficiency in children has been defined as serum 25(OH) D levels of over 30 ng/ml, insufficiency as 21-30 ng/ml, deficiency as less than 20 ng/ml. The upper limit of the reference range is 100 nmol/L, as levels above may be associated with vitamin D toxicity in children. Serum 1.25(OH)2D should not be used for the assessment of vitamin D status. Natural sources of vitamin D are very limited, therefore, its use in the form of nutritional supplements is the primary mean of preventing and treating rickets. The recommended drug for the prevention and treatment of vitamin D deficiency is cholecalciferol (D3). Colecalciferol is recommended to be given at a dose of 1000 IU/day to all children aged 1 to 6 months regardless of the type of feeding or the season of the year to prevent vitamin D deficiency. This article presents modern ways of preventing, diagnosing and treating rickets.

Exploring the burden of X-linked hypophosphatemia: a European multi-country qualitative study

IntroductionX-linked hypophosphatemia (XLH) is a rare, lifelong, progressive disease characterised by renal phosphate wasting and abnormal bone mineralisation. Symptoms begin in early childhood, with the development of rickets and related skeletal deformities and reduced growth, progressing to long-term complications, including pseudofractures and fractures, as well as pain, stiffness and fatigue. The present study was designed to explore the patient experience of pain, stiffness and fatigue and the psychosocial impact of XLH in detail.MethodsA cross-sectional qualitative study was conducted in the United Kingdom (18), Finland (6), France (4), Germany (1) and Luxembourg (1) with XLH patients aged 26 and over. Interview discussion guides were developed in consultation with clinical experts and patient associations. Data were analysed thematically.ResultsParticipants (N = 30) described pain, stiffness and fatigue as frequently experienced symptoms with a significant impact on physical functioning and activities of daily living (ADLs). Some also described the symptoms as impacting their mood/mental health, relationships, social life and leisure activities. Participants described how common symptoms could interact or aggravate other symptoms. Symptoms had often worsened over time, and for many, were associated with concern about the future. Most participants were worried or felt guilty about having children with XLH. The findings confirmed and extended the existing model of the burden of XLH.ConclusionThe present study is the first to provide an in-depth analysis of pain, stiffness and fatigue, their impact and the interrelatedness of these symptoms among adults with XLH. The study also described the psychosocial impact of XLH as a hereditary, lifelong progressive disease.

Rickets in a Crab-eating Fox (Cerdocyon thous)

Background : Calcium is essential for the healthy development of animals, especially regarding bone formation. Diverse factors influence calcium metabolism, and failure in any of these points may result in metabolic bone diseases. Rickets is an uncommon disease of growing bones occurring exclusively in young animals, it is a characterized by the failure of osteoid to calcify and can be a result of lack of vitamin D, imbalance of calcium and phosphorus or hereditary conditions. Nutritional origin is more frequent in veterinary medicine, but it has become rarer after the availability of balanced commercial rations. This report describes the diagnosis and treatment of rickets in a crab-eating fox puppy. Case : A 3-month-old male crab-eating fox was presented with ataxia and angular deviation of the tibia and radius/ulna with suspected osteometabolic disease. It was part of a group of three orphan siblings hand-raised. The other two siblings did not present any clinical signs. All three animals presented pale mucous membranes and were infected by ancylostoma, coccidia, toxocara, and sarcocystis. Radiographic findings of the affected animal showed generalized osteopenia of the entire skeleton associated with widening radiolucent distal physeal plates and cupping of the metaphysis, changes classical of rickets. The other two siblings presented no skeletal alterations and complete blood count and biochemistry of all three animals were taken for comparison, including serum vitamin D and PTH. All three animals presented lymphopenia (5.4-9.3 x 10³/uL, reference range 10.3-16.5 x 10³/uL), hypoproteinemia (5.1-5.3 g/dL, reference range 5.9-8.2 g/dL), low levels of creatinine (0.4-0.6 mg/dL, reference range 0.7-1.2 mg/dL), increased ALP (181-285 U/L, reference range 209.7-267 U/L) and CK (421-500 U/L, reference range for domestic dogs 16-140 U/L). The affected fox presented ionized calcium (10.9 mg/dL, reference range for domestic dogs 9.3-11.5 mg/dL) and vitamin D (26.4 ng/mL, reference range for domestic dogs 9.5-129 ng/mL) close to the inferior limits associated with elevated phosphorus (8.8 mg/dL, reference range for domestic dogs 2.5-5.6 mg/dL) and PTH (4.3 pg/mL, reference range for domestic dogs < 2.82 pg/dL). Besides that, the affected animal presented the quickest development (weight gain) among the offspring. Discussion : Recent reports of rickets in veterinary medicine are not common. The advent of balanced commercial rations and improvement in animal husbandry reduced the frequency of this condition. Wild species are more frequently reported to present metabolic bone disease due to inadequate nutrition management of the different species. Bone formation and growth are result of the deposition of hydroxyapatite crystals and it depends on calcium intake or absorption, adequate serum vitamin D levels and proper calcium and phosphorus balance. All these three situations were breached in this case report, resulting in a multifactorial scenario for development of rickets in this crab-eating-fox. Radiographic exam, complete blood count, biochemistry, and clinical response to dietary correction confirmed the diagnosis of rickets with nutritional origin. Hereditary rickets had been described in people and a domestic dog, but not in wildlife species. The animal responded well to clinical and nutritional management, presenting clinical response within a couple of weeks. This is the first report of rickets in this species as well as dosage of serum vitamin D and PTH in crab-eating foxes.

Acute Phosphate Restriction Impairs Bone Formation and Increases Marrow Adipose Tissue in Growing Mice.

Phosphate plays a critical role in chondrocyte maturation and skeletal mineralization. Studies examining the consequences of dietary phosphate restriction in growing mice demonstrated not only the development of rickets, but also a dramatic decrease in bone accompanied by increased marrow adipose tissue (MAT). Thus studies were undertaken to determine the effects of dietary phosphate restriction on bone formation and bone marrow stromal cell (BMSC) differentiation. Acute phosphate restriction of 28-day-old mice profoundly inhibited bone formation within 48 hours. It also resulted in increased mRNA expression of the early osteolineage markers Sox9 and Runt-related transcription factor 2 (Runx2), accompanied by decreased expression of the late osteolineage markers Osterix and Osteocalcin in BMSCs and osteoblasts, suggesting that phosphate restriction arrests osteoblast differentiation between Runx2 and Osterix. Increased expression of PPARγ and CEBPα, key regulators of adipogenic differentiation, was observed within 1 week of dietary phosphate restriction and was followed by a 13-fold increase in MAT at 3 weeks of phosphate restriction. In vitro phosphate restriction did not alter BMSC osteogenic or adipogenic colony formation, implicating aberrant paracrine or endocrine signaling in the in vivo phenotype. Because BMP signaling regulates the transition between Runx2 and Osterix, this pathway was interrogated. A dramatic decrease in pSmad1/5/9 immunoreactivity was observed in the osteoblasts of phosphate-restricted mice on day 31 (d31) and d35. This was accompanied by attenuated expression of the BMP target genes Id1, KLF10, and Foxc2, the latter of which promotes osteogenic and angiogenic differentiation while impairing adipogenesis. A decrease in expression of the Notch target gene Hey1, a BMP-regulated gene that governs angiogenesis, was also observed in phosphate-restricted mice, in association with decreased metaphyseal marrow vasculature. Whereas circulating phosphate levels are known to control growth plate maturation and skeletal mineralization, these studies reveal novel consequences of phosphate restriction in the regulation of bone formation and osteoblast differentiation. © 2016 American Society for Bone and Mineral Research.

Toxicity of aflatoxin B1 towards the vitamin D receptor (VDR)

This research describes an unexpected toxicity of the aflatoxin B1 towards the vitamin D receptors. Rickets is a childhood disease, and calcium deficiency is the aetiological cause in Africa, being primarily associated with nutritional problems; in this research the contribution of aflatoxin B1 exposure during the early months of life is an interesting factor to deepen in order to prevent liver damages or the development of rickets. The results show that the expression of vitamin D receptor in osteosarcoma cell line SAOS-2 is significantly down-modulated by exposure to aflatoxin B1. This seems to suggest that Aflatoxin B1, toxic towards the vitamin D receptor, interferes with the actions of the vitamin D on calcium binding gene expression in the kidney and intestine. Experimental data indicate a 58% and 86% decrease if the cells are exposed to 5 ng/mL and 50 ng/mL of aflatoxin B1, respectively. These results seem to indicate that natural occurrence of the aflatoxin B1 and allelic variant of vitamin D receptor on (F allele) increase the risk of developing rickets of African children.

Ghrelin Levels in Patients with Rickets

Rickets is a common metabolic bone disease in infants. The predominant cause of rickets is vitamin D deficiency. Vitamin D is required for bone formation. The role of ghrelin in bone metabolism is unclear, but it may have an indirect effect. There are also reports in the literature suggesting that ghrelin acts directly on osteoblasts as a positive regulator. To evaluate the relationship between ghrelin levels and the development of rickets. We evaluated the relationship between serum/ saliva ghrelin levels and rickets in a cohort of 10 patients aged 6-24 months with nutritional rickets and completely healthy 14 children. Plasma ghrelin levels were measured using a commercial radioimmunoassay kit. The saliva ghrelin measurements were performed using a Human-ghrelin- radioimmunoassay-sensitive kit. Ghrelin levels in blood and saliva were found significantly lower in the rickets group compared to the healthy subjects in this study. Findings of this study shows that there is a relationship between ghrelin and the development of rickets. Decreased ghrelin levels may have caused to poor infant appetite and impaired nutritional status. Furthermore the absence of ghrelin\'s calciotropic effects may have contributed to the development of rickets. Detailed studies with larger series are warranted to support these findings.

Role of Calcium Deficiency in Development of Nutritional Rickets in Indian Children: A Case Control Study

Nutritional rickets is usually attributed to vitamin D deficiency. Studies from some tropical countries have postulated low dietary intake of calcium as the cause of nutritional rickets. Both vitamin D and dietary calcium deficiency are highly prevalent in India. Information on their relative contribution in the development of rickets in Indian children is limited. The aim was to study the role of calcium and vitamin D deficiency in causation of nutritional rickets in young Indian children. In a case-control study, 67 children with nutritional rickets and 68 age- and sex-matched healthy controls were compared for demographic factors, nutritional status, sun exposure (UV score), dietary calcium and phytate intake (for subjects not breast-fed at presentation), and biochemical parameters [serum calcium, inorganic phosphate, alkaline phosphatase, 25-hydroxyvitamin D (25OHD), and PTH]. Mean intake of calcium (204±129 vs. 453±234 mg/d; P<0.001) and proportion of calcium from dairy sources (41.7 vs. 88.6%; P<0.001) were significantly lower in cases vs. controls. The dietary intake of phytate was also significantly higher in cases (P=0.01). Median serum 25OHD level (interquartile range) in both cases and controls was in the range of deficiency [13.7 (10; 17.9) and 19.4 (12.3; 24.6) ng/ml, respectively]. There was no significant difference in the serum 25OHD level (P=0.08) or sun exposure as measured by UV score (P=0.39) among the cases and controls. In cases with rickets, significant negative correlations were seen between dietary calcium intake and radiological score (r=-0.28; P=0.03) and PTH (r=-0.26; P=0.02). No correlation was found between serum 25OHD level and radiological score or biochemical parameters of rickets. Rickets develops when low dietary calcium intake coexists with a low or borderline vitamin D nutrition status.

Linear and Skull Growth in Extremely Low Birth Weight Babies with Rickets of Prematurity

Preterm birth results in poor accretion of bone minerals and development of rickets of prematurity. Poor skeletal growth is one of the long term morbidities of this condition, which is said to have a lesser effect on the skull growth. The present study was a retrospective observational study to compare the effect of rickets of prematurity on the linear and skull growth in the first year of life. In this retrospective analysis, 1 y follow-up records of extremely low birth weight (ELBW) babies born in five consecutive years and their anthropometric data were evaluated. ELBW babies with confirmed rickets of prematurity were taken as the study group and those without were taken as the control group and anthropometric values (head size and length) at various ages in the first year of life were compared using relevant statistical software. Both the lengths and head sizes of the babies in the two groups were found to be comparable until the age of 12 mo.

Tipos de Raquitismo, Aspectos Dentários e Histológicos: Revisão de Literatura

Introduction: A disease that occurs during childhood, rickets is the failure of growing bone to mineralize. Many skeletal and radiographic changes can ocur because of the lack of calcified osteoid and the buildup of unossified cartilage. Proper bone formation requires a complex interplay of several organs and chemicals, and vitamin D deserves special mention because any disturbance in its production, absorption, or metabolism is paramount in the development of rickets. The pathophysiology of the disease is thought to be impaired phosphate transport, especially decreased phosphate resorption in the renal proximal tubule, as well as in the intestine. In most cases, the diagnosis is established with a thorough history and physical examination and confirmed by laboratory evaluation. Early diagnosis is essential because morbidity can be minimized if children are treated before eight months of age. Objective: The aim of this literature review is to present various types of rickets with clinical features and the dental findings, preventive measurements and treatments. Conclusion: The dentist as well as the pediatrician should be made aware of the features of this disorder so that early intervention can prevent subsequent serious and more invasive dental procedures.

Sunlight exposure and development of rickets in Indian toddlers

To study the role of sunlight exposure in determining the vitamin D status of underprivileged toddlers. Height and weight were measured, clinical examination was performed, Food Frequency Questionnaire was administered and history of sunlight exposure was obtained in all (61) toddlers attending daytime crèche (Group B). Ionised calcium (iCa), inorganic Phosphorous (iP), alkaline phosphatase activity (ALP), serum parathyroid hormone (PTH) and 25 Hydroxy vitamin D (25OHD) were measured. Data were compared with results of a survey measuring similar parameters in 51 (of 251 eligible) toddlers from the same slum (Group A). 111 children (mean age 2.6 yr (0.7), boys 56) were studied. Prevalence of hypovitaminosis D was 77% in group B toddlers (46 of 60) and 16.4% (10 of 61) had rickets, while none of the group A toddlers had 25OHD levels below 30 nmol/L. Four children (7.8%) from Group A as against 24 (42.9%) from Group B, had sunshine exposure of < 30 minutes per day. Underprivileged toddlers who were deprived of sunlight had a much greater incidence of hypovitaminosis D and frank rickets. The study has important public health implications and underscores the necessity for sunlight exposure in young children.

Sun safety: what are the health messages?

Solar ultraviolet radiation (UVR) is a human carcinogen. The UK and the worldwide incidence of cutaneous (skin) melanoma are rising. It is now the second most common cancer in 15-34 year-olds in the UK, increasing by 49% in 1991-2000. The UK government prioritized skin cancer in 1992 in their public health strategy The Health of the Nation, and set the target for reducing the yearly rise in skin cancer incidence by 2005. In 1998 in the Saving Lives: Our Healthier Nation strategy, targets were set to reduce the death rate from cancer, including skin cancer, by 20% by 2010. As a consequence of these targets, since the mid-1990s public health campaigns to reduce sun exposure and skin cancer incidence in the UK have used specific interventions for at-risk groups and the mass media to reach the general population. Evidence indicates a shift in knowledge, with further work required to increase change in behaviour and attitudes. An associate health problem is vitamin D deficiency, which is prevalent across certain UK population groups. The main childhood health problem associated with vitamin D deficiency is the development of rickets, with evidence indicating those at high risk are exclusively breastfed dark-skinned infants, the elderly, those with dark skin pigmentation, and certain cultural groups that cover their bodies in clothing. Adolescents are the group with the highest incidence of low vitamin D status in the UK, with children of Asian descent at higher risk than Caucasian children. Increasing the outdoor activity levels of children in winter and during the cooler hours in summer is one way of increasing safe sun exposure. It is imperative to educate the general public on the risk of vitamin D deficiency, and offer advice on safe sun exposure, dietary sources of vitamin D, and dietary supplements. More research is required on recommendations for daily vitamin D supplements to determine optimal vitamin D levels in different population groups. There also needs to be reliable and accessible evidence on the links between vitamin D deficiency and lack of sun exposure, with sun safe messages adjusted accordingly.

Maternal vitamin D deficiency associated with neonatal hypocalcaemic convulsions

Maternal vitamin D insufficiency is not uncommon. Infants born to mothers who are deficient in vitamin D and or calcium, usually due to cultural modifications in their diets or clothing habits, and in addition are breastfed, are at risk of developing vitamin D deficiency and hypocalcaemia. We present a case of neonatal hypocalcaemic seizures secondary to vitamin D deficiency.Rickets in children resulting from vitamin D deficiency is well documented. It is also becoming clear that there is a positive correlation between maternal vitamin D status during pregnancy and lactation and the development of rickets both in infancy and childhood. The correlation between maternal vitamin D, neonatal vitamin D and hypocalcaemia is not well documented.

25‐OH‐D3, calcium, phosphorus, and alkaline phosphatase content in sera from captive polar bear (Ursus maritimus) cubs at the Denver Zoological Foundation

After the development of rickets in two hand-reared polar bear (Ursus maritimus) cubs at the Denver Zoological Foundation we initiated a project opportunistically evaluating sera 25-OH-D(3), calcium, phosphorus, and alkaline phosphatase levels in seven mother-reared polar bear cubs. From one to three serum samples were obtained while the cub was still in the den with no access to natural sunlight and one after the cub exited the den. The sera 25-OH-D(3) increased as the cubs grew (108+/-37 nmol/L [n=7] while in den, 184.6+/-48.3 nmol/L [n=7] out of the den) but were substantially lower then captive adults (348+/-215 nmol/L [n=36]) or free-ranging adults (360+/-135 nmol/L [n=56]). We found that age was correlated significantly with 25-OH-D(3) levels but den status (in or out) was not significant. Sera calcium and phosphorus values were highest in denned cubs (calcium, 2.9+/-0.4 mmol/L [n=13]; phosphorus, 3.1+/-0.5 mmol/L [n=13]) and then declined as the cubs matured and left the den (calcium, 2.5+/-0.1 mmol/L [n=7]; phosphorus, 2.4+/-0.4 mmol/L [n=7]). The enzyme alkaline phosphatase (presumably the bone isoenzyme) was high in denned growing cubs (831+/-426 IU/L [n=13]) and then declined gradually as the cubs aged and exited the den (96+/-83 IU/L [n=7]). Zoo Biol 0:1-7, 2007. (c) 2007 Wiley-Liss, Inc.

Vitamin D Receptor Polymorphism among Rickets Children in Mongolia

BACKGROUNDIt was reported that 32% of children under five years old in Mongolia had symptoms of rickets. Vitamin D receptor (VDR) gene polymorphism has received attention in relation to bone metabolism. We therefore investigated whether VDR polymorphism is related to high prevalence of rickets in Mongolia and to bone properties in childhood.METHODSWe conducted a case-control study in Ulaanbaatar involving 80 children aged 7-10 years with a history of rickets (cases) and 72 children with no history of rickets (controls). VDR polymorphism was assessed using BsmI, ApaI, and TaqI, and bone properties were determined by measuring age-standardized midtibial cortical speed of sound (TCSOS).FINDINGSEach allelic frequency was verified to satisfy the Hardy-Weinberg equilibrium in cases, controls, and the total sample. The VDR polymorphisms among cases (BB 3%, Bb 18%, bb 80%; AA 15%, Aa 38%, aa 47%; and TT 81 %, Tt 17%, tt 3%) did not differ significantly from those among controls (BB 1%, Bb 13%, bb 86%; AA 16%, Aa 46%, aa 38%; and TT 86%, Tt 13%, tt 1%). There were no significant differences in TCSOS according to the VDR genotype among either cases or controls.CONCLUSIONSThe VDR polymorphism does not play a major role in the development of rickets in Mongolia and has no effect on TCSOS in childhood.

Nutritional rickets: nature or nurture?

Rickets is a mineralization disorder of the growing bone. Nutritional rickets is still prevalent in many parts of the world. Although vitamin D deficiency plays a central role in the pathogenesis of this disease, calcium deficiency and genetic factors may also cause or contribute to the development of rickets. This review will focus on the classical form of nutritional rickets: vitamin D deficiency rickets. Epidemiology, ethiopathogenesis, risk factors, the current clinical picture, diagnosis, treatment and prevention of nutritional rickets will be reviewed.