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. Objective sample Methodology 413988 413 988 413,98 25OHD OHD OH 1 012014 01 2014 01/201 102018 10 2018 10/201 Laboratory population ngmL ng mL deficient gender group 292 29 29. 92 9 9. 08 8 0.8 125 5 12.5 females evident winter 36 found Conclusion life 41398 41 98 413,9 01201 201 01/20 10201 10/20 0. 12. 3 4139 4 413, 0120 01/2 1020 10/2 012 01/ 102 10/

Objective: To investigating the relationship between α-Klotho and FGF-23 with bone biochemical markers and bone density findings in extremely aged individuals. Methods: A total of 55 individuals with a mean age of 85.6 years were subjected to clinical, biochemical, and bone mineral density analyses and the enzyme-linked immunosorbent assay-based detection of α-Klotho and FGF-23. The mean, standard deviation, median, and interquartile ranges of the sample values were determined, and Spearman's test for association assessments was used for statistical analysis. Results: The study participants expressed median FGF-23 and α-Klotho levels of 69.81 RU/mL (51.43 RU/mL) and 733.43 pg/mL (360.83 pg/mL), respectively. The majority of the participants possessed osteopenia (54.5%) and a vitamin D deficiency (57%). The 25-hydroxyvitamin D concentrations ranged between 7.1 and 47.5ng/mL, with a median of 18.1ng/mL. Conclusion: No substantial associations were discovered between α-Klotho and FGF-23 levels and bone density in the study participants. Objective αKlotho α Klotho FGF23 FGF 23 FGF-2 Methods 5 856 85 6 85. clinical enzymelinked enzyme linked assaybased assay based FGF23. 23. deviation determined Spearmans Spearman s analysis Results 6981 69 81 69.8 RUmL RU mL 51.43 5143 51 43 (51.4 73343 733 733.4 pgmL pg 360.83 36083 360 83 (360.8 pg/mL, , pg/mL) respectively 54.5% 545 54 (54.5% 57%. 57 57% . (57%) 25hydroxyvitamin hydroxyvitamin 25 71 7 1 7. 475ngmL ngmL 47 5ng ng 47.5ng/mL 181ngmL 18 1ng 18.1ng/mL Conclusion FGF2 2 FGF- 8 698 69. 51.4 514 4 (51. 7334 73 733. 360.8 3608 36 (360. 54.5 (54.5 (57% 51. (51 360. 3 (360 54. (54. (57 (5 (36 (54 ( (3

ABSTRACT Hypophosphatasia (HPP) is an inherited disease caused by a low activity of tissue-nonspecific alkaline phosphatase, a hydrolase that removes phosphate groups from many molecules. Decreased alkaline phosphatase activity leads to the accumulation of three main metabolites, i.e., pyridoxal 5'-phosphate (PLP), inorganic pyrophosphate (PPi), and phosphoethanolamine. Impairment in PLP dephosphorylation induces seizures, while PPi accumulation inhibits bone mineralization. Clinically, HPP has a wide spectrum of presentations, ranging from neonatal death to an apparent lack of symptoms. This disease is classified into six subtypes according to the age at onset of first signs or symptoms. The clinical manifestations of the disease include rickets-like bone changes, bone demineralization, fragility fractures, reduced muscular strength, chest deformity, pulmonary hypoplasia, nephrolithiasis, nephrocalcinosis, and chondrocalcinosis. Treatment of HPP consists of enzyme replacement therapy. Before this therapy was approved, treatment was palliative and associated with high morbidity and mortality. Asfotase alfa has changed the prognosis of the disease by reducing bone deformity and improving bone mineralization, lung function, and muscle weakness, among other benefits. In adults, teriparatide and anti-sclerostin antibody have been used off-label in selected cases, demonstrating benefit in accelerating fracture healing and in concomitant treatment of osteoporosis. This review summarizes the main aspects of HPP and identifies the particularities of the disease in adult patients. (HPP tissuenonspecific tissue nonspecific molecules metabolites ie i e i.e. 5phosphate 5 PLP, , (PLP) PPi, (PPi) phosphoethanolamine seizures mineralization Clinically presentations symptoms ricketslike rickets like changes demineralization fractures strength hypoplasia nephrolithiasis nephrocalcinosis chondrocalcinosis approved mortality function weakness benefits adults antisclerostin anti sclerostin offlabel off label cases osteoporosis patients i.e (PLP (PPi

ABSTRACT Objective: This study aimed to investigate the association between 25OHD (total, bioavailable and free) with bone mass and microarchitecture among primary hyperparathyroidism (PHPT) patients and controls. Subjects and methods: Sixty-four patients in the preoperative period of PHPT and 63 matched controls, who had not taken vitamin D in the last three months. To calculate the bioavailable and free 25OHD, the genetic variants of the vitamin D-binding protein (DBP) were determined. Bone mineral density (BMD) was determined by dual-energy X-ray absorptiometry (DXA). The distributions of total, bioavailable and free 25OHD and their correlation with TBS and DXA were evaluated. Results: PHPT showed BMD and TBS values lower than CTRL in all locations (p < 0.05). There were no statistical differences in the levels of free, bioavailable and total 25OHD between the PHPT and CTRL groups [mean, min-max: 3.4 (1.4-8.6) vs. 3.1 (1.0-9.8) pg/mL, 1.51 (0.43-3.58) vs. 1.41 (0.38-3.48) ng/mL, 22.6 (11.0-39.9) vs. 20.6 (8.9-35.3) ng/dL, respectively; (p > 0.05). The distribution of DBP haplotypes was similar between groups. DXA showed no correlation with any form of 25OHD in both groups. TBS presented a weak correlation with the total 25OHD in PHPT (r = 0.28; p = 0.02) and a moderate correlation with the total, free and bioavailable 25OHD in CTRL (r = 0.42; r = 0.42; r = 0.43; respectively, p < 0.01). Conclusion: The concentrations of total, free and bioavailable 25OHD were similar in both the PHPT and control groups. 25OHD concentrations correlated positively with TBS and not with DXA, especially in controls, suggesting that this method may be more sensitive to assessing the consequences of vitamin D deficiency on bone quality in individuals without PHPT. Objective OHD (total (PHPT controls methods Sixtyfour Sixty four 6 months Dbinding binding (DBP (BMD dualenergy dual energy Xray X ray DXA. . (DXA) evaluated Results 0.05. 005 0.05 0 05 0.05) mean, mean [mean minmax min max min-max 34 3 4 3. 1.48.6 1486 1.4 8.6 1 8 (1.4-8.6 vs 31 1.09.8 1098 1.0 9.8 9 (1.0-9.8 pgmL pg mL pg/mL 151 51 1.5 0.433.58 043358 0.43 3.58 43 58 (0.43-3.58 141 41 0.383.48 038348 0.38 3.48 38 48 (0.38-3.48 ngmL ng ng/mL 226 22 22. 11.039.9 110399 11.0 39.9 11 39 (11.0-39.9 206 20 20. 8.935.3 89353 8.9 35.3 35 (8.9-35.3 ngdL dL ng/dL respectively 0.28 028 28 0.02 002 02 0.42 042 42 043 0.01. 001 0.01 01 0.01) Conclusion (DXA 00 0.0 1.48. 148 14 1. 86 8. (1.4-8. 09 1.09. 109 10 98 9. (1.0-9. 15 5 433 0.433.5 04335 0.4 358 3.5 (0.43-3.5 383 0.383.4 03834 038 0.3 348 (0.38-3.4 2 039 11.039. 11039 110 11. 399 39. (11.0-39. 935 8.935. 8935 89 353 35. (8.9-35. 0.2 04 0. 1.48 (1.4-8 1.09 (1.0-9 0.433. 0433 (0.43-3. 0.383. 0383 03 (0.38-3. 11.039 1103 (11.0-39 93 8.935 893 (8.9-35 (1.4- (1.0- 0.433 (0.43-3 0.383 (0.38-3 11.03 (11.0-3 8.93 (8.9-3 (1.4 (1.0 (0.43- (0.38- (11.0- (8.9- (1. (0.43 (0.38 (11.0 (8.9 (1 (0.4 (0.3 (11. (8. ( (0. (11 (8 (0

ABSTRACT Vitamin D deficiency is a general health problem affecting individuals at all stages of life and on different continents. The musculoskeletal effects of vitamin D are well known. Its deficiency causes rickets, osteomalacia, and secondary hyperparathyroidism and increases the risk of fractures. Clinical and experimental evidence suggests that vitamin D performs multiple extraskeletal functions. Several tissues unrelated to calcium and phosphate metabolism express vitamin D receptor (VDR) and are directly or indirectly influenced by 1,25(OH)2D (calcitriol). Some also express the enzyme 1 alpha-hydroxylase (CYP27B1) and produce 1,25(OH)2D, inducing autocrine or paracrine effects. Among the pleiotropic effects of vitamin D are the regulation of cell proliferation and differentiation, hormone secretion, and immune function. In this review, we outline vitamin D physiology and the outcomes of recent large RCTs on its potential extraskeletal effects. Those studies exhibit a need for continued clinical analysis to elucidate whether vitamin D status can influence extraskeletal health. Longer longitudinal follow-up and standardized assays are crucial to better assess potential outcomes.

ABSTRACT Objective: The fibroblast growth factor 23 (FGF23) has been related to biological aging, but data in elderly individuals are scant. We determined the profile of serum FGF23 levels in a population of very-old individuals and studied their correlations with parameters of bone metabolism and health markers, as functional performance. Materials and methods: This cross-sectional study was performed on 182 community dwellers aged ≥ 80 years. Serum levels of FGF23, PTH, calcium, albumin, phosphorus, creatinine, bone markers, and bone mineral density data were analyzed. Physical performance was evaluated with the stationary march (Step), Flamingo, and functional reach tests, along with questionnaires to assess falls and fractures in the previous year, energy expenditure (MET), and the Charlson index (CI). Physical activity was evaluated with the International Physical Activity Questionnaire (IPAQ). Results: Most participants (75%) had FGF23 levels between 30-120 RU/mL (range: 6.0-3,170.0 RU/mL). FGF23 levels correlated with estimated glomerular filtration rate (eGFR; r = -0.335; p = 0.001) and PTH (r = 0.318; p < 0.0001). Individuals with FGF23 in the highest tertile had more falls in the previous year (p = 0.032), worse performance in the Flamingo (p = 0.009) and Step (p < 0.001) tests, worse CI (p = 0.009) and a trend toward sedentary lifestyle (p = 0.056). On multiple regression, FGF23 tertiles remained significant, independently of eGFR, for falls in the previous year, performance in the Flamingo and stationary march tests, lean mass index, and IPAQ classification. Conclusion: In a population of very elderly individuals, FGF23 levels were inversely associated with neuromuscular and functional performances. Higher concentrations were related to more falls, lower muscle strength and aerobic capacity, and poorer balance, regardless of renal function, suggesting a potentially deleterious role of high FGF23 concentrations in musculoskeletal health. Objective 2 FGF (FGF23 aging scant FGF2 veryold old markers methods crosssectional cross sectional 18 8 years calcium albumin phosphorus creatinine analyzed Step, , (Step) tests MET, MET (MET) CI. . (CI) IPAQ. (IPAQ) Results 75% 75 (75% 30120 30 120 30-12 RUmL RU mL range (range 6.03,170.0 6031700 6.0 3,170.0 6 0 3 170 6.0-3,170. RU/mL. RU/mL) eGFR (eGFR 0.335 0335 335 -0.335 0.001 0001 001 0.318 0318 318 0.0001. 00001 0.0001 0.0001) 0.032, 0032 0.032 032 0.032) 0.009 0009 009 0.056. 0056 0.056 056 0.056) regression significant classification Conclusion performances capacity balance function (FGF2 1 (Step (MET (CI (IPAQ 7 (75 3012 12 30-1 03 6.03,170. 603170 60 6. 31700 3,170. 17 6.0-3,170 0.33 033 33 -0.33 0.00 000 00 0.31 031 31 0000 0.000 003 0.03 005 0.05 05 (FGF (7 301 30- 6.03,170 60317 3170 3,170 6.0-3,17 0.3 -0.3 0.0 ( 6.03,17 6031 317 3,17 6.0-3,1 0. -0. 6.03,1 603 3,1 6.0-3, -0 6.03, 3, 6.0-3 - 6.03 6.0-

Abstract Objective: To present an updated and evidence-based guideline for the use of dual-energy x-ray absorptiometry (DXA) to assess body composition in clinical practice. Materials and methods: This Official Position was developed by the Scientific Committee of the Brazilian Association of Bone Assessment and Metabolism ( Associação Brasileira de Avaliação Óssea e Osteometabolismo , ABRASSO) and experts in the field who were invited to contribute to the preparation of this document. The authors searched current databases for relevant publications in the area of body composition assessment. In this second part of the Official Position, the authors discuss the interpretation and reporting of body composition parameters assessed by DXA and the use of DXA for body composition evaluation in special situations, including evaluation of children, persons with HIV, and animals. Conclusion: This document offers recommendations for the use of DXA in body composition evaluation, including indications, interpretation, and applications, to serve as a guiding tool in clinical practice and research for health care professionals in Brazil.

RESUMO Objetivo Examinar a associação entre o fator de crescimento de fibroblastos 23 sérico e a capacidade funcional em indivíduos independentes, com 80 anos ou mais. Métodos A capacidade funcional de 144 idosos foi avaliada por meio de Atividades Instrumentais da Vida Diária, testes cognitivos, força de preensão manual e capacidade de levantar de uma cadeira e sentar cinco vezes. O fator de crescimento de fibroblastos 23 foi medido pelo teste ELISA. Resultados Os participantes no tercil mais baixo de fator de crescimento de fibroblastos 23 tiveram a maior média±desvio-padrão da taxa de filtração glomerular estimada, concentração média de hemoglobina mais alta, menor número médio de doenças e menor número de medicamentos utilizados. Em participantes com taxa de filtração glomerular estimada >45mL/minuto/1,73m2, o nível médio do fator de crescimento de fibroblastos 23 foi maior naqueles com 25(OH) vitamina D <20ng/mL do que naqueles com 25(OH) vitamina D ≥20ng/mL (75,6RU/mL±42,8 versus 68,5RU/mL±41,7; p<0,001). Houve aumento na cistatina C sérica média (de 1,3mg/mL±0,3 a 1,5mg/mL±0,3 a 1,7mg/mL±0,4) em função do tercil de fator de crescimento 23 de fibroblastos mais alto (p<0,001). Os níveis de fator de crescimento de fibroblastos 23 não foram significativamente associados à capacidade em testes físicos ou cognitivos. Conclusão Em idosos independentes residentes na comunidade ≥80 anos, o fator de crescimento de fibroblastos 23 foi associado a comorbidades relacionadas à idade e à função renal, mas não à capacidade funcional.

ABSTRACT Objective To examine the association of between serum fibroblast growth factor 23 and the functional capacity among independent individuals, aged 80 or older. Methods The functional capacity of 144 elderly was assessed by Instrumental Activities of Daily Living, cognitive tests, handgrip strength and the timed ability to rise from a chair and sit down five times. Fibroblast growth factor 23 was measured using an ELISA assay. Results Participants in the lowest fibroblast growth factor 23 tertile had the highest mean±standard deviation estimated glomerular filtration rate, the highest mean hemoglobin level, the lowest average number of diseases and the lowest number of medications used. In participants with the estimated glomerular filtration rate >45mL/minute/1.73m2, mean fibroblast growth factor 23 level was higher in those with 25(OH) vitamin D <20ng/mL than in those with 25(OH) vitamin D ≥20ng/mL (75.6RU/mL±42.8 versus 68.5RU/mL±41.7; p<0.001). There was an increase in the mean serum cystatin C (from 1.3mg/mL±0.3 to 1.5mg/mL±0.3 to 1.7mg/mL±0.4) as function of higher fibroblast growth factor 23 tertile (p<0.001). Fibroblast growth factor 23 levels were not significantly associated with capacity in physical or cognitive tests. Conclusion In independent community-dwelling elderly, aged ≥80 years, fibroblast growth factor 23 was associated with aged-related comorbidities and renal function but not with functional capacity.

ABSTRACT Antiresorptive therapy is the main form of prevention of osteoporotic or fragility fractures. Medication-related osteonecrosis of the jaw (MRONJ) is a relatively rare but severe adverse reaction to antiresorptive and antiangiogenic drugs. Physicians and dentists caring for patients taking these drugs and requiring invasive procedures face a difficult decision because of the potential risk of MRONJ. The aim of this study was to discuss the risk factors for the development of MRONJ and prevention of this complication in patients with osteoporosis taking antiresorptive drugs and requiring invasive dental treatment. For this goal, a task force with representatives from three professional associations was appointed to review the pertinent literature and discuss systemic and local risk factors, prevention of MRONJ in patients with osteoporosis, and management of established MRONJ. Although scarce evidence links the use of antiresorptive agents in the context of osteoporosis to the development of MRONJ, these agents are considered a risk factor for this complication. Despite the rare reports of MRONJ in patients with osteoporosis, the severity of symptoms and impact of MRONJ in the patients' quality of life make it imperative for health care professionals to consider this complication when planning invasive dental procedures.

SUMMARY Hypophosphatasia (HPP) is a rare disease with a high mortality rate in its severe forms. It is caused by mutations within the gene encoding the tissue-nonspecific alkaline phosphatase (TNSALP), an enzyme responsible for bone mineralization. In 2015, the Food and Drug Administration approved the use of asfotase alfa, the first medication showing benefit in the treatment of HPP. We describe a case with a 2-year follow-up of the first Brazilian child treated with asfotase alfa. A 5-year-old boy, born to consanguineous parents, was diagnosed with HPP at the age of 20 months. During prenatal ultrasonography, polyhydramnios and shortening of long bones were detected. After birth, he presented delayed motor development, repeated respiratory infections, and bone deformities. At the age of 2 years and 8 months, he started walking and had already lost his primary teeth. He had reduced levels of alkaline phosphatase (ALP), elevated levels of pyridoxal 5’-phosphate (PLP), and a p.Ala33Val (c.98C>T) missense mutation in homozygosis in the TNSALP gene. His parents and sister also had reduced ALP levels, high PLP levels, and the same mutation in heterozygosis. His father and sister were healthy, and his mother was diagnosed with rickets in childhood, which resulted in short physical stature and lower limb deformities. The patient was started on asfotase alfa at the age of 2 years and 10 months. After 2 years of treatment, he improved his motor skills, had no further episodes of severe respiratory infection, and showed improved radiological findings of rickets, without any severe side effect.

ABSTRACT The effects of vitamin D on the musculoskeletal system are well established. Its deficiency causes osteomalacia, secondary hyperparathyroidism, and an increased risk for fractures and falls. However, clinical and experimental evidence points to extra-skeletal actions of vitamin D, including on immune and respiratory systems. Thus, during this COVID-19 pandemic, a possible deleterious role of vitamin D deficiency has been questioned. This paper aims to present a brief review of the literature and discuss, based on evidence, the role of vitamin D in the lung function and in the prevention of respiratory infections. Relevant articles were searched in the databases MEDLINE/PubMed and SciELO/LILACS. The mechanisms of vitamin D action in the immune system response will be discussed. Clinical data from systematic reviews and meta-analyses show benefits in the prevention of respiratory infections and improvement of pulmonary function when vitamin D-deficient patients are supplemented. At the time of writing this paper, no published data on vitamin D supplementation for patients with COVID-19 have been found. Vitamin D supplementation is recommended during this period of social isolation to avoid any deficiency, especially in the context of bone outcomes, aiming to achieve normal values of 25(OH)D. The prevention of respiratory infections and improvement of pulmonary function are additional benefits observed when vitamin D deficiency is treated. Thus far, any protective effect of vitamin D specifically against severe COVID-19 remains unclear. We also emphasize avoiding bolus or extremely high doses of vitamin D, which can increase the risk of intoxication without evidence of benefits.

ABSTRACT Hypovitaminosis D is a common condition with a negative impact on health. This statement, prepared by experts from the Brazilian Society of Endocrinology and Metabolism and the Brazilian Society of Clinical Pathology/Laboratory Medicine, includes methodological aspects and limitations of the measurement of 25-hydroxyvitamin D [25(OH)D] for identification of vitamin D status, and identifies individuals at increased risk for deficiency of this vitamin in whom 25(OH)D measurement is recommended. For the general population, 25(OH)D levels between 20 and 60 ng/mL are considered normal, while individuals with levels below 20 ng/mL are considered to be vitamin D deficient. This statement identifies potential benefits of maintaining 25(OH)D levels > 30 ng/mL in specific conditions, including patients aged > 65 years or pregnant, those with recurrent falls, fragility fractures, osteoporosis, secondary hyperparathyroidism, chronic kidney disease, or cancer, and individuals using drugs with the potential to affect the vitamin D metabolism. This statement also calls attention to the risk of vitamin D intoxication, a life-threatening condition that occurs at 25(OH)D levels above 100 ng/mL

ABSTRACT Objective: To verify which component of body composition (BC) has greater influence on postmenopausal women bone mineral density (BMD). Subjects and methods: Four hundred and thirty women undergoing treatment for osteoporosis and 513 untreated women, except for calcium and vitamin D. Multiple linear regression analysis was performed in order to correlated BMD at lumbar spine (LS), total femur (FT), femoral neck (FN) with body mass (BM), total lean mass (LM) and total fat mass (FM), all determined by DXA. Results: BM significantly correlated with all bone sites in untreated and treated women (r = 0.420 vs 0.277 at LS; r = 0.490 vs 0.418 at FN, r = 0.496 vs 0.414 at FT, respectively). In untreated women, the LM correlated better than FM with all sites, explaining 179% of LS; 32.3% of FN and 30.2% of FT; whereas FM explained 13.2% of LS; 277% of FN, 23.4% of FT In treated women, correlations with BC were less relevant, with the LM explaining 6.7% of BMD at LS; 15.2% of FN, 16% of FT, whereas the FM explained 8.1% of LS; 179% of FN and 176% of FT. Conclusion: LM in untreated women was better predictor of BMD than FM, especialy for distal femur, where it explained more than 30% of the BMD, suggesting that maintaining a healthy muscle mass may contribute to decrease osteoporosis risk. Treatment with anti-osteoporotic drugs seems to mask these relationships. Arch Endocrinol Metab. 2018;62(4):431-7

ABSTRACT Objective To present an update on the diagnosis and treatment of hypoparathyroidism based on the most recent scientific evidence. Materials and methods The Department of Bone and Mineral Metabolism of the Sociedade Brasileira de Endocrinologia e Metabologia (SBEM; Brazilian Society of Endocrinology and Metabolism) was invited to prepare a document following the rules set by the Guidelines Program of the Associação Médica Brasileira (AMB; Brazilian Medical Association). Relevant papers were retrieved from the databases MEDLINE/PubMed, LILACS, and SciELO, and the evidence derived from each article was classified into recommendation levels according to scientific strength and study type. Conclusion An update on the recent scientific literature addressing hypoparathyroidism is presented to serve as a basis for the diagnosis and treatment of this condition in Brazil.