Alert for the high prevalence of vitamin D deficiency in adolescents in a large Brazilian sample

Abstract Objective: To estimate the prevalence of vitamin D deficiency and severe deficiency in children and adolescents, in a large Brazilian sample. Methodology: Results of 413,988 25(OH)D measurements in children and adolescents aged 0 to 18 years collected between 01/2014 and 10/2018 were obtained from the database of a Clinical Laboratory. In this population, 25 hydroxyvitamin D concentrations below 20 ng/mL are considered deficient, and below 12 ng/mL as severe deficiency. All measurements were performed by immunoassay and the results were distributed by gender, age group, seasonality, and latitude. Results: The mean of 25(OH)D levels was 29.2 ng/mL with a standard deviation of 9.2 ng/mL. Of the total samples, 0.8% had a concentration < 12 ng/mL, and 12.5% of the samples had a concentration < 20 ng/mL, with a higher prevalence in females. Children under 2 years of age had the lowest prevalence. The effects of latitude and seasonality were quite evident. In samples of female adolescents from the southern region in winter, 36% of vitamin D deficiency and 5% of severe deficiency were found. Conclusion: In this large number of measurements of 25(OH)D in children and adolescents, 12.5% had a deficiency and 0.8% had severe deficiency. A greater deficiency was observed among adolescents, especially females, which raises questions about the need for supplementation during this period of life.

Clinical spectrum of hypocalcaemia in children

Background: Hypocalcaemia is a biochemical abnormality commonly seen in paediatric population with a multi-factorial etiology having varied presentation ranging from acute emergency to chronic diagnostic dilemma. We studied the clinical profile of infants and children presenting with hypocalcaemia from 0 to 12 years of age. Methods: Clinical features, risk factors, precipitating factors, feeding/dietary practices of all children (0-12 years) visiting our tertiary care centre, from January 2019 to March 2020, diagnosed with hypocalcaemia were recorded and a correlation with serum calcium levels was studied. Results: Out of 92 patients having hypocalcaemia majority 57 (62%) were males. Majority of participants belonged to age group of 6 months-2 years i.e. 40 (43.48%). The commonest presentation was convulsions present in 39 (42.39%) participants affecting more children less than 2 years of age; whereas majority of children above 2 years of age presented with growth impairment. Risk factors identified were perinatal risk factors, faulty feeding practices in infants, inadequate dietary calcium intake in children, inadequate sun exposure. Amongst the biochemical factors precipitating hypocalcaemia, alkalosis showed significant association (p value 0.016) with degree of hypocalcaemia; most common etiology was vitamin D deficiency and nutritional rickets. Conclusions: Hypocalcemia plays vital role in infants and growing children because of its various implications on growth and development. Exposure to sunlight, vitamin D and calcium supplementation during pregnancy and lactation and infancy with good dietary calcium intake for children during their growth spurts can prevent complications. Health education and awareness of common risk factors for hypocalcaemia can prove helpful.

Evaluation of Burosumab in the treatment of X-linked hypophosphatemic rickets in children / 中华内分泌代谢杂志

Objective:To evaluate the efficacy and safety of Burosumab in patients with X-linked hypophosphatemic rickets.Methods:Clinical data of 9 children diagnosed with X-linked hypophosphatemic rickets and treated with Burosumab in the Department of Pediatric Nephrology, Anhui Children′s Hospital from November 2021 to September 2023 were retrospectively analyzed, including the general information, clinical manifestations, auxiliary examination, Burosumab treatment and follow-up.Results:Among the 9 cases, there were 5 males and 4 females, with a median age at diagonosis of 2 years. After traditional treatment, the fluctuation of serum phosphorus ranged from 0.7 to 0.9 mmol/L. The median age at the initiation of Burosumab treatment was 2.8 years, and the initial dosage was 0.8 mg/kg, administrated subcutaneously every 2 weeks. The laboratory and imaging indexes were improved after 6 months of Burosumab treatment, and the mean serum phosphorus level increased from(0.81±0.14) mmol/L to(1.02±0.10) mmol/L at 1 month( t=3.85, P=0.001) and(1.14±0.25) mmol/L at 6 months( t=3.58, P=0.002). The average alkaline phosphatase(ALP) level decreased from(509.89±110.10) U/L before treatment to(447.89±106.76) U/L after 1 month( t=1.21, P=0.243). After 6 months, the ALP level significantly decreased to(385.89±60.33) U/L ( t=2.96, P=0.009). The average height percentile increased from 18.42±10.09 before treatment to 26.56±16.59 after 6 months( t=1.26, P=0.227). Rachitis severity scores of both lower limbs ranged from 4.61±1.36 before treatment to 3.06±1.51 after 6 months( t=2.29, P=0.036). No serious adverse events occurred during treatment. Conclusion:Burosumab is safe and effective in treating X-linked hypophosphatemic rickets, exhibiting minimal side effects and significant clinical applicability value.

X-linked hypophosphatemic rickets treated with Burosumab in early childhood: A case study with 18-month follow up / 中华内分泌代谢杂志

Objective:To retrospectively analyze a pediatric case of X-linked hypophosphatemic rickets treated with Burosumab and improve clinicians′ awareness of the safety and effectiveness of the drug.Methods:Clinical data of the child were collected. Whole-exon genetic testing after parental consent confirmed X-linked hypophosphatemic rickets. During 18 months of Burosumab treatment, fasting blood phosphorus, alkaline phosphate, calcium, and calcium phosphate product were monitored every 11-14 days. Parathyroid hormone and 25 hydroxyvitamin D were checked every 2-6 weeks, while knee spacing, liver and kidney function, urinary calcium creatinine ratio, electrocardiogram were assessed every 3 months. Radiological imaging was performed every 6 months, with continuous follow-up of the child.Results:Whole-exon sequencing results showed a c. 1080_1081insCAATGTTA(p.T361Qfs*3) spontaneous heterozygous frameshift mutation in the PHEX gene in the child, which has not been reported previously. After the patient was treated with Burosumab for 18 months, the biochemical indexes were significantly improved, and the rickets score was reduced, without gingival abscess or other adverse events.Conclusion:The variant c. 1080_1081insCAATGTTA(p.T361Qfs*3) in the PHEX gene was identified as the cause of the patient′s condition. Burosumab, as a targeted therapeutic agent for X-linked hypophosphatemic rickets, showed significant treatment efficacy.

Refractory Rickets

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

A case report on anti-epileptic drugs associated cerebral palsy and rickets

Seizures are incredibly widespread all around the world, today. A seizure is often described as a transient alteration in the electrical activity of the brain. This required the treatment with antiepileptic drugs (AEDs). The majority of AEDs lower vitamin D levels. Vitamin D is found to be crucial for intestinal absorption of calcium, magnesium, and phosphate which helps to build and mineralize bones. Vitamin D deficiency has been seen to be a causative reason for cerebral palsy which is a neurological illness that affects movement and muscle coordination, permanently. It has been observed to manifest in infancy or early childhood due to vitamin D deficiency due to long term use of AEDs making it severe due to malnourishment. This case reports the use of antiepileptic drugs leading to cerebral palsy due to vitamin D deficiency. Therefore, by this case report we want to alert the readers and healthcare professionals about the possible adverse effects of AEDs and to be aware of them.

Primer reporte en Argentina de variante patógena en DMP1 asociada a raquitismo hipofosfatémico autosómico recesivo / First report in Argentina of a pathogenic DMP1 variant associated with autosomal recessive hypophosphatemic rickets

El raquitismo hipofosfatémico hereditario es una condición genética asociada con una mineralización ósea alterada causada por la deficiencia de fosfato. Produce deformidad esquelética y retraso del crecimiento en la infancia. Se describen diferentes patrones de herencia según el locus involucrado. Dado el solapamiento de los fenotipos y la dificultad en analizar genealogías reducidas, los estudios moleculares son importantes para establecer la causa genética y realizar el abordaje familiar. La forma recesiva del raquitismo hipofosfatémico (ARHR, OMIM #241520) es una condición extremadamente poco frecuente reportada en familias de origen europeo y de Oriente Medio. Las mutaciones con pérdida de función del gen DMP1 (dentin matrix acidic phosphoprotein 1) se asocian al raquitismo hipofosfatémico hereditario tipo 1. En este artículo presentamos el primer reporte de una familia argentina con raquitismo hipofosfatémico hereditario por mutación en DMP1

Hereditary hypophosphatemic rickets is a genetic condition associated with impaired bone mineralization caused by phosphate deficiency. It results in skeletal deformity and growth retardation in early childhood. Different inheritance patterns have been described according to the locus involved. Given the phenotypic overlapping and the difficulty in analyzing reduced genealogies, molecular studies are important to establish the genetic cause and implement a family-centered approach. The autosomal recessive form of hypophosphatemic rickets (ARHR, OMIM 241520) is an extremely rare condition reported in families of European and Middle Eastern descent. Loss-of-function mutations in the DMP1 (dentin matrix acidic phosphoprotein 1) gene are associated with hereditary hypophosphatemic rickets type 1. In this article, we describe the first report of an Argentine family with hereditary hypophosphatemic rickets due to a mutation in the DMP1 gene.

An unusual case of familial hypophosphatemic rickets

Rickets is the failure of mineralisation of osteoid and newly formed bones in a child skeleton. It is commonly associated with vitamin D deficiency; however, it can be because of a decrease in serum phosphate level leading to inadequate mineralization of cartilage and bone, consequent skeletal deformities and growth retardation. In hypophosphatemic rickets, there are both inherited and acquired forms, where X-linked hypophosphatemic rickets (XLH) is the most prevalent genetic form and caused by mutations in the phosphate-regulating endopeptidase (PHEX) gene. XLH is associated with growth retardation and bone deformities. This rare variety was diagnosed in a 2 year 4 month old child who had brought by parents with complaint of abnormal gait. In the present case, clinical and radiographic aspects of manifestation of familial hypophosphatemic rickets are discussed.

Prevalence and Correlates of Vitamin D Deficiency Among Children and Adolescents From a Nationally Representative Survey in India

Objective: To evaluate the prevalence of vitamin D deficiency (VDD) and its correlates among apparently healthy children and adolescents. Methods: We carried out a secondary analysis of data of Comprehensive National Nutrition Survey 2016-18 to analyze the pre-valence and predictors of VDD among Indian children and adolescents. Results: The over-all prevalence of VDD in preschool children (1-4 years), school age (5-9 years) children, and adolescents (10-19 years) was 13.7%, 18.2%, and 23.9%, respectively. Age, living in urban area, and winter season were significantly associated with VDD. Vegetarian diet and high-income households were the main risk factors observed in 5-19 years age category. Female sex and less than three hour of physical activity/week were independent risk factors among adolescents. Conclusion: The prevalence and determinants of VDD across different age-groups are reported, and these should be interpreted and addressed to decrease the burden of VDD in India.

Vitamin D dependent rickets type 2: a case-based review of patient with alopecia and rickets

Vitamin D dependent rickets (VDDR) type 2 is a very rare hereditary disease which has an autosomal recessive mode of inheritance. Patients with VDDR type 2 have a mutation in the gene encoding for vitamin D receptor on chromosome 12q12-q14, thus averting normal physiological action of 1,25 vitamin D. It's presents with the developmental delay in motor domain with features of rickets usually in the first year of life. Alopecia totalis has a frequent association with the disease. We are reporting a case of a 5-year-old boy who has a history of difficulty walking since 2 year of life, with a gradually progressive motor weakness course. Patients have a history of alopecia since 2 months of age, which progressed to alopecia totalis. On investigation, serum calcium was 7.2 mg/dl with a very high alkaline phosphate level of 1065 IU/ML with a normal vitamin D level was reported. The initial treatment started with IV calcium followed by 1000mg of oral calcium, along with a high dose of calcitriol. The patient was under periodic follow-up showing improvement in biochemical parameters. We reviewed literature of seven patient out of which 5 patients had alopecia and found 2 patients had enamel hypoplasia and all had features of rickets.

Raquitismo hipofosfatémico familiar ligado al cromosoma X: Reporte de Caso

El Fósforo es regulado por el riñón y el sistema óseo orquestado principalmente por la acción de la parathormona (PTH) y una molécula recientemente descrita como el factor de crecimiento fibroblástico 23 (FGF-23) . Presentamos los casos de dos pacientes madre-hijo con Raquitismo hipofosfatémico ligado al cromosoma X. Se realizó el estudio genético identificándose una mutación en el Gen PHEX: variante patogénica tipo splicing en hemicigosis: mutación previamente descrita como HGMD CS126536. El Raquitismo Hipofosfatémico forma parte de un grupo de tubulopatías caracterizadas hiperfosfaturia. La mutación del gen PHEX con pérdida de función conduce al aumento de FGF-23. PHEX degrada el FGF-23 en fragmentos inactivos, evitando la excreción excesiva de fosfatos y el desarrollo de hipofosfatemia. En un paciente con hipofosfatemia no dependiente de la hormona PTH o de la vitamina D y de presentación familiar debe considerarse el diagnóstico de Raquitismo hipofosfatémico ligado al cromosoma X.

Phosphate is regulated by the kidneys and the osseus system, mainly due to the action of parathyroid hormone (PTH) and a recently described molecule, fibroblast growth factor 23 (FGF-23). We present the cases of two patients, mother and son with X-chromosome linked hypophosphatemic rickets. The genetic study was performed, and a mutation in the PHEX gene was identified, a splicing type pathogenic variant in hemizygosis. This mutation was previously described as HGMD CS126536. Hypophosphatemic rickets belongs to a group of tubulopathies characterized by hyperphosphaturia. PHEX gene mutation with function loss leads to increased FGF-23 levels. PHEX degrades FGF-23 into inactive fragments, preventing excessive phosphate excretion and the development of hypophosphatemia. In patients with PTH or vitamin D non- dependent hypophosphatemia, a diagnosis of X-chromosome linked hypophosphatemic rickets should be considered.

Value of serum fibroblast growth factor 23 in diagnosis of hypophosphatemic rickets in children / 中国当代儿科杂志

OBJECTIVES@#To study the value of serum fibroblast growth factor 23 (FGF23) in the diagnosis of hypophosphatemic rickets in children.@*METHODS@#A total of 28 children who were diagnosed with hypophosphatemic rickets in Children's Hospital of Nanjing Medical University from January 2016 to June 2021 were included as the rickets group. Forty healthy children, matched for sex and age, who attended the Department of Child Healthcare of the hospital were included as the healthy control group. The serum level of FGF23 was compared between the two groups, and the correlations of the serum FGF23 level with clinical characteristics and laboratory test results were analyzed. The value of serum FGF23 in the diagnosis of hypophosphatemic rickets was assessed.@*RESULTS@#The rickets group had a significantly higher serum level of FGF23 than the healthy control group (P<0.05). In the rickets group, the serum FGF23 level was positively correlated with the serum alkaline phosphatase level (rs=0.38, P<0.05) and was negatively correlated with maximum renal tubular phosphorus uptake/glomerular filtration rate (rs=-0.64, P<0.05), while it was not correlated with age, height Z-score, sex, and parathyroid hormone (P>0.05). Serum FGF23 had a sensitivity of 0.821, a specificity of 0.925, an optimal cut-off value of 55.77 pg/mL, and an area under the curve of 0.874 in the diagnosis of hypophosphatemic rickets (P<0.05).@*CONCLUSIONS@#Serum FGF23 is of valuable in the diagnosis of hypophosphatemic rickets in children, which providing a theoretical basis for early diagnosis of this disease in clinical practice.

Advances in vitamin K and bone metabolism in children / 国际儿科学杂志

Vitamin K(VK)occurs naturally in two forms, including vitamin K 1(VK 1)and vitamin K 2(VK 2). The function of VK is related to the number of its side chains.In addition to the function of coagulation, VK is also gradually found to be involved in bone metabolism, which is closely related to the occurrence of adult osteoporosis.The rapid growth and development in childhood is a period of extremely vigorous bone metabolism.The role of VK in children′s bone metabolic diseases has been gradually recognized in recent years.However, there are still few clinical studies on the level of VK in children of different ages and how VK participates in children′s bone metabolic diseases.This article reviews the types and metabolism of VK, the mechanism of VK regulating bone metabolism, the level of VK and its role in bone metabolic diseases, so as to provide new understanding and ideas for the prevention and treatment of bone health in children.

A pedigree of X-linked dominant hypophosphatemic osteomalacia / 中华全科医师杂志

A 53-year woman and her 18-year daughter presenting with bone pain, bone fractures, bone deformities and short stature were admitted to Gansu Provincial People′s Hospital in March 2021. Laboratory tests showed low blood phosphorus, low renal phosphorus threshold, normal or low blood calcium, and normal or increased PTH. The high-throughput sequencing indicated heterozygous mutations of the PHEX gene (Phosphate-regulating gene with Homology to Endopeptidases on the X chromosome) in two patients, which was not detected in other family members; finally the diagnosis of X-linked dominant hypophosphatemic rickets/osteomalacia(XLH)was confirmed for these two patients. Treated with neutral phosphorus solution and Rocaltrol, bone pain was relieved completely in the younger patient, but not for her mother due to long disease course and severe complications. Because of the large heterogeneity of the disease there are high missed diagnosis and misdiagnosis rates for XLH. In this paper a pedigree of XLH is reported with literature review.

Sunlight Exposure vs Oral Vitamin D Supplementation for Prevention of Vitamin D Deficiency in Infancy: ARandomized Controlled Trial

Objective: To compare the efficacy of sunlight exposure and oral vitamin D3 supplementation to achieve vitamin D sufficiency in infants at 6 months of age. Design: Open-label randomized controlled trial. Setting: Public hospital in Northern India (28.7°N). Participant: Breastfed infants at 6-8 weeks of age. Intervention: Randomized to receive sunlight exposure (40% body surface area for a minimum of 30 minutes/week) or oral vitamin D3 supplementation (400 IU/day) till 6 months of age. Outcome: Primary - proportion of infants having vitamin D sufficiency (>20 ng/mL). Secondary - proportion of infants developing vitamin D deficiency (<12ng/mL) and rickets in both the groups at 6 months of age. Results: Eighty (40 in each group) infants with mean (SD) age 47.8 (4.5) days were enrolled. The proportion of infants with vitamin D sufficiency increased after intervention in the vitamin D group from 10.8% to 35.1% (P=0.01) but remained the same in sunlight group (13.9%) and was significant on comparison between both groups (P=0.037). The mean (SD) compliance rate was 72.9 (3.4)% and 59.7 (23.6)% in the vitamin D and sunlight group, respectively (P=0.01). The geometric mean (95% CI) serum 25(OH) D levels in the vitamin D and sunlight group were 16.23 (13.58-19.40) and 11.89 (9.93-14.23) ng/mL, respectively; (P=0.02), after adjusting baseline serum 25(OH)D with a geometric mean ratio of 1.36 (1.06-1.76). Two infants in sunlight group developed rickets. Conclusion: Oral vitamin D3 supplementation is more efficacious than sunlight in achieving vitamin D sufficiency in breastfed infants during the first 6 months of life due to better compliance.

New treatments for rare bone diseases: hypophosphatemic rickets/osteomalacia

Abstract Phosphorus is one of the most abundant minerals in the human body; it is required to maintain bone integrity and mineralization, in addition to other biological processes. Phosphorus is regulated by parathyroid hormone, 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], and fibroblast growth factor 23 (FGF-23) in a complex set of processes that occur in the gut, skeleton, and kidneys. Different molecular mechanisms - overproduction of FGF-23 by tumors responsible for oncogenic osteomalacia, generation of an FGF-23 mutant that is resistant to cleavage by enzymes, and impaired FGF-23 degradation due to a reduction in or loss of the PHEX gene - can lead to FGF-23-stimulating activity and the consequent waste of urinary phosphate and low levels of 1,25(OH)2D3. Conventional treatment consists of multiple daily doses of oral phosphate salts and vitamin D analogs, which may improve radiographic rickets but do not normalize growth. Complications of the conventional long-term treatment consist of hypercalcemia, hypercalciuria, nephrolithiasis, nephrocalcinosis, impaired renal function, and potentially chronic kidney disease. Recently, burosumab, an antibody against FGF-23, was approved as a novel therapy for children and adults with X-linked hypophosphatemia and patients with tumor-induced osteomalacia. Burosumab showed good performance in different trials in children and adults. It increased and sustained the serum phosphorus levels, decreased the rickets severity and pain scores, and improved mineralization. It offers a new perspective on the treatment of chronic and disabling diseases. Arch Endocrinol Metab. 2022;66(5):658-65

Dental and Endodontic Management in a Patient with Familial X-Linked Hypophosphatemic Rickets

ABSTRACT: The term rickets refers to insufficient or retarded mineralization of the osteoide matrix. X-linked hypophosphatemic (XLH) rickets is a rare genetic disorder characterized by biochemical changes in bone mineralization due to inactivation of the phosphate regulating gene and primary defect of the osteoblasts. The aim of this article was to report a clinical case of XLH, its oral manifestations, periapical changes and dental management. A 31-year old woman female patient was referred to the school of dentistry with pain and sensitivity in the teeth. She had a childhood history of rickets, hypophosphatemia and alteration in Vitamin D. In the oral exam, enamel hypoplasia, microdontia, fistula, caries and periapical lesions and periodontal disease were diagnosed. The radiographic and tomographic exams exhibited the presence of periapical lesions involving various teeth with radiolucent images, suggestive of granuloma or periapical cysts. The treatme nt prioritized the urgency of eliminating pain and removing the foci of infection. Endodontic treatment began in the teeth that had fistula or periapical lesions and in parallel, oral hygiene guidance was provided and periodontal treatment was performed. There was an improvement in the clinical condition with reduction in inflammation and mobility of the teeth. Dentists and health professionals must evaluate the patient as a whole, considering the relations between systemic and oral health. Knowledge of systemic diseases associated with rickets and their characteristics is essential for making a correct oral diagnosis and planning the dental treatment.

RESUMEN: El término raquitismo se refiere a la mineralización insuficiente o retardada de la matriz osteoide. El raquitismo hipofosfatémico ligado al cromosoma X (XLH) es un trastorno genético caracterizado por cambios bioquímicos en la mineralización ósea debido a la inactivación del gen regulador del fosfato y al defecto primario de los osteoblastos. El objetivo de este artículo fue reportar un caso clínico de XLH, sus manifestaciones orales, cambios periapicales y manejo dental. La paciente, una mujer de 31 años, acudió a la Clínica de Semiología de la UFPR con dolor y sensibilidad en varios dientes. Tenía antecedentes infantiles de raquitismo, hipofosfatemia y alteración de la vitamina D. En el examen oral se diagnosticó hipoplasia del esmalte, microdoontia, fístula, caries y lesiones periapicales y enfermedad periodontal. Los exámenes radiográficos y tomográficos mostraron la presencia de lesiones periapicales en varios dientes con imágenes radiolúcidas, sugestivas de granuloma o quistes periapicales. El tratamiento priorizó la urgencia de eliminar el dolor y remover los focos de infección. Se inició tratamiento de endodoncia en los dientes que presentaban fístula o lesiones periapicales y paralelamente se brindó orientación de higiene oral y se realizó tratamiento periodontal. Hubo una mejoría en la condición clínica con reducción de la inflamación y movilidad de los dientes. Los odontólogos y profesionales de la salud deben evaluar al paciente como un todo, teniendo en cuenta las relaciones entre salud sistémica y oral. El conocimiento de las enfermedades sistémicas asociadas al raquitismo y sus características es fundamental para realizar un correcto diagnóstico oral y planificar el tratamiento odontológico.

Guideline for the diagnosis and management of hypophosphatemic rickets/osteomalacia / 中华内分泌代谢杂志

Hypophosphatemic rickets/osteomalacia is a group of rare chronic metabolic bone diseases, which has detrimental impact on the growth, mobility, and life quality of the patients. Because of its rarity, the public awareness remains low, so does in general physician, which leads to delayed diagnosis and treatment. With a vision to standardize the diagnosis and treatment of hypophosphatemic rickets/osteomalacia, Chinese Society of Endocrinology and Chinese Society of Osteoporosis and Bone Mineral Research convened a national group of experts to compose this guideline based on current evidence, which covered the pathogenesis, diagnosis, treatment and management of hypophosphatemic rickets/osteomalacia. In summary, this work outlines recommendations for clinicians, aiming to improve the management of hypophosphatemic rickets/osteomalacia in China.

La accidentada historia del descubrimiento de la vitamina D, en su primer centenario / The checkered history of the discovery of vitamin D, in its first centenary

El año 2022 marca el primer centenario del descubrimiento de la vitamina D, hallazgo que recompensó la prolongada búsqueda de la causa del raquitismo, su prevención y tratamiento. Al mismo tiempo puso en marcha importantes investigaciones relaciona-das con su biotransformación y el mecanismo de su acción antirraquítica, además de estudios sobre diversos efectos biológicos sin relación directa con su papel en la salud ósea. Esta breve revisión se limitará a delinear la prehistoria de la vitamina D y los diversos estudios, básicos y clínicos, que condujeron a su descubrimiento y caracterización química. (AU)

The year 2022 marks the centenary of the discovery of vitamin D, a breakthrough that rewarded the long search for the cause of rickets, its prevention and treatment. At the same time, it launched important investigations related to its biotransformation and the mechanism of its antirachitic action, as well as studies on various biological effects without direct relation to its role in bone health. This brief review will be limited to an outline of the prehistory of vitamin D and the various basic and clinical studies that led to its discovery and chemical characterization. (AU)