Vitamin D for the Prevention of Disease: An Endocrine Society Clinical Practice Guideline.

BACKGROUND: Numerous studies demonstrate associations between serum concentrations of 25-hydroxyvitamin D (25[OH]D) and a variety of common disorders, including musculoskeletal, metabolic, cardiovascular, malignant, autoimmune, and infectious diseases. Although a causal link between serum 25(OH)D concentrations and many disorders has not been clearly established, these associations have led to widespread supplementation with vitamin D and increased laboratory testing for 25(OH)D in the general population. The benefit-risk ratio of this increase in vitamin D use is not clear, and the optimal vitamin D intake and the role of testing for 25(OH)D for disease prevention remain uncertain. OBJECTIVE: To develop clinical guidelines for the use of vitamin D (cholecalciferol [vitamin D3] or ergocalciferol [vitamin D2]) to lower the risk of disease in individuals without established indications for vitamin D treatment or 25(OH)D testing. METHODS: A multidisciplinary panel of clinical experts, along with experts in guideline methodology and systematic literature review, identified and prioritized 14 clinically relevant questions related to the use of vitamin D and 25(OH)D testing to lower the risk of disease. The panel prioritized randomized placebo-controlled trials in general populations (without an established indication for vitamin D treatment or 25[OH]D testing), evaluating the effects of empiric vitamin D administration throughout the lifespan, as well as in select conditions (pregnancy and prediabetes). The panel defined "empiric supplementation" as vitamin D intake that (a) exceeds the Dietary Reference Intakes (DRI) and (b) is implemented without testing for 25(OH)D. Systematic reviews queried electronic databases for publications related to these 14 clinical questions. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology was used to assess the certainty of evidence and guide recommendations. The approach incorporated perspectives from a patient representative and considered patient values, costs and resources required, acceptability and feasibility, and impact on health equity of the proposed recommendations. The process to develop this clinical guideline did not use a risk assessment framework and was not designed to replace current DRI for vitamin D. RESULTS: The panel suggests empiric vitamin D supplementation for children and adolescents aged 1 to 18 years to prevent nutritional rickets and because of its potential to lower the risk of respiratory tract infections; for those aged 75 years and older because of its potential to lower the risk of mortality; for those who are pregnant because of its potential to lower the risk of preeclampsia, intra-uterine mortality, preterm birth, small-for-gestational-age birth, and neonatal mortality; and for those with high-risk prediabetes because of its potential to reduce progression to diabetes. Because the vitamin D doses in the included clinical trials varied considerably and many trial participants were allowed to continue their own vitamin D-containing supplements, the optimal doses for empiric vitamin D supplementation remain unclear for the populations considered. For nonpregnant people older than 50 years for whom vitamin D is indicated, the panel suggests supplementation via daily administration of vitamin D, rather than intermittent use of high doses. The panel suggests against empiric vitamin D supplementation above the current DRI to lower the risk of disease in healthy adults younger than 75 years. No clinical trial evidence was found to support routine screening for 25(OH)D in the general population, nor in those with obesity or dark complexion, and there was no clear evidence defining the optimal target level of 25(OH)D required for disease prevention in the populations considered; thus, the panel suggests against routine 25(OH)D testing in all populations considered. The panel judged that, in most situations, empiric vitamin D supplementation is inexpensive, feasible, acceptable to both healthy individuals and health care professionals, and has no negative effect on health equity. CONCLUSION: The panel suggests empiric vitamin D for those aged 1 to 18 years and adults over 75 years of age, those who are pregnant, and those with high-risk prediabetes. Due to the scarcity of natural food sources rich in vitamin D, empiric supplementation can be achieved through a combination of fortified foods and supplements that contain vitamin D. Based on the absence of supportive clinical trial evidence, the panel suggests against routine 25(OH)D testing in the absence of established indications. These recommendations are not meant to replace the current DRIs for vitamin D, nor do they apply to people with established indications for vitamin D treatment or 25(OH)D testing. Further research is needed to determine optimal 25(OH)D levels for specific health benefits.

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

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.

An update on clinical presentation and responses to therapy of patients with hereditary hypophosphatemic rickets with hypercalciuria (HHRH).

Pathogenic variants in solute carrier family 34, member 3 (SLC34A3), the gene encoding the sodium-dependent phosphate cotransporter 2c (NPT2c), cause hereditary hypophosphatemic rickets with hypercalciuria (HHRH). Here, we report a pooled analysis of clinical and laboratory records of 304 individuals from 145 kindreds, including 20 previously unreported HHRH kindreds, in which two novel SLC34A3 pathogenic variants were identified. Compound heterozygous/homozygous carriers show above 90% penetrance for kidney and bone phenotypes. The biochemical phenotype for heterozygous carriers is intermediate with decreased serum phosphate, tubular reabsorption of phosphate (TRP (%)), fibroblast growth factor 23, and intact parathyroid hormone, but increased serum 1,25-dihydroxy vitamin D, and urine calcium excretion causing idiopathic hypercalciuria in 38%, with bone phenotypes still observed in 23% of patients. Oral phosphate supplementation is the current standard of care, which typically normalizes serum phosphate. However, although in more than half of individuals this therapy achieves correction of hypophosphatemia it fails to resolve the other outcomes. The American College of Medical Genetics and Genomics score correlated with functional analysis of frequent SLC34A3 pathogenic variants in vitro and baseline disease severity. The number of mutant alleles and baseline TRP (%) were identified as predictors for kidney and bone phenotypes, baseline TRP (%) furthermore predicted response to therapy. Certain SLC34A3/NPT2c pathogenic variants can be identified with partial responses to therapy, whereas with some overlap, others present only with kidney phenotypes and a third group present only with bone phenotypes. Thus, our report highlights important novel clinical aspects of HHRH and heterozygous carriers, raises awareness to this rare group of disorders and can be a foundation for future studies urgently needed to guide therapy of HHRH.

Hypophosphatasia: from birth to adulthood.

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.

Concentrations of total, bioavailable, and free 25OHD in individuals with and without primary hyperparathyroidism and their correlations to DXA and trabecular bone score.

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.

Levels of bioavailable, and free forms of 25(OH)D after supplementation with vitamin D3 in primary hyperparathyroidism.

The 25 hydroxyvitamin D [25(OH)D] is the major metabolite for ascertaining vitamin D status, which circulates bound to a specific carrier (vitamin D-binding protein - VDBP). A portion that circulates unbound vary according to the VDBP genotype. This study evaluates the behavior of different forms of 25(OH)D, before and after supplementation with 14,000 IU of vitamin D3, weekly for 12 weeks, in individuals with primary hyperparathyroidism and controls. Fifty-six patients with active primary hyperparathyroidism (PHPT) and 64 paired controls (CTRL), not taking vitamin D3 for the last three months, were enrolled. The genetic isotypes of VDBP were determined to calculate bioavailable and free 25(OH)D. A p < 0.05 was considered significant. There were no statistical differences in free, bioavailable, and total 25(OH)D levels between PHPT and CTRL groups at baseline. The distribution of VDBP haplotypes 1s/1s, 1f/1f, 1s/1f, 2/2, 1s/2, and 1f/2 was similar between groups. After supplementation, all three forms of 25(OH)D proportionally increased within each group, although the percentage increment was lower in the PHPT group (p < 0.05). Total 25(OH)D is better correlated with PTH in the PHPT group than bioavailable and free 25(OH)D (r = -0.41; p < 0.05). The concentrations of total, free, and bioavailable 25(OH)D were similar in both PHPT and CTRL groups, and all forms increased proportionally after supplementation, although this increment percentage was higher in the CTRL group, with a subsequent reduction of PTH and AP. Total 25(OH)D correlated better with PTH than other forms, suggesting no advantages in measuring free or bioavailable 25(OH)D in these situations.

Vitamin D in the older population: a consensus statement.

BACKGROUND: This paper reports results from the 5th International Conference "Controversies in Vitamin D" that was held in Stresa, Italy, 15-18 September 2021. The conference is part of this series that started in 2017 and has been conducted annually since. The objective of these conferences is to identify timely and controversial topics related to Vitamin D. Dissemination of the results of the conference through publications in peer-reviewed journals is an important means by which the most up to date information can be shared with physicians, investigators, and other health care professionals. Vitamin D and aging, the subject of this paper was featured at the conference. METHODS: Participants were selected to review available literature on assigned topics related to vitamin D and aging and to present their findings with illustrative material, the intent of which was to stimulate discussion and to arrive at a consensus. The presentations were directed towards the following areas: impact of aging on vitamin D production and levels; skeletal effects of vitamin D deficiency in the older population; falls and vitamin D in the aging; potential extra skeletal effects of vitamin D; and strategies to prevent vitamin D deficiency. A final topic was related to how vitamin D might influence the efficacy of vaccines for Covid-19. RESULTS: Hypovitaminosis D can lead to several skeletal and extra-skeletal outcomes. Older adults are at risk for vitamin D deficiency as both production and metabolism of vitamin D change with aging due to factors, such as reduced sun exposure and reduced production capacity of the skin. Skeletal consequences of these age-related changes can include reduced bone mineral density, osteomalacia and fractures. Potential extra-skeletal effects can include added risks for falls, reduced muscle strength, diabetes, cancer, and cardiovascular disease. Strategies to avoid these vitamin D deficiency-related negative outcomes include sun exposure, food fortification, and supplementation. While aging does not diminish sufficient reserve capacity for cutaneous vitamin D production, concerns about skin cancers and practical matters for the institutionalized elderly limit this option. Supplementation with vitamin D is the best option either pharmacologically or through food fortification. Regardless of treatment strategies, interventions to restore sufficient vitamin D status will show positive results only in those who are truly deficient. Thus, treatment goals should focus on avoiding 25(OH)D serum levels <30 nmol/l, with a goal to reach levels >50 nmol/l. CONCLUSIONS: The results of this conference has led to consensus on several issues. Vitamin D supplementation should be combined with calcium to reduce fractures in the older population. The goal for adequate Vitamin D status should be to reach a serum level of 25(OH)D >50 nmol/l. It appears that daily low-dose vitamin D regimens reduce the risk of falling, especially in the elderly, compared with infrequent, large bolus doses that may increase it. The role of Vitamin D supplementation on muscle strength remains to be clarified. On the other hand, supplementation decreases the risk of progression to T2D from prediabetes among those who are Vitamin Ddeficient. Of three possible strategies to establish vitamin D sufficiency - sunshine exposure, food fortification, and supplementation - the latter seems to be the most effective and practical in the aging population.

Serum 25 hydroxyvitamin D concentrations in individuals over 80 years old and their correlations with musculoskeletal and health parameters.

PURPOSE: The present study aims to evaluate the serum concentrations of 25 hydroxyvitamin D[25(OH)D] in individuals aged ≥80 years, independent, free-living in Sao Paulo, Brazil (Lat 23.5 oS), and to investigate their associations with musculoskeletal system, physical performance and health markers. METHOD: This cross-sectional study included 212 community dwellers aged ≥80 years and evaluated serum 25(OH)D, PTH, calcium, albumin, phosphorus, creatinine, bone markers, and bone mineral density. Physical performance was evaluated with stationary march, Flamingo, and functional reach tests, questionnaires to assess falls and fractures in the previous year, energy expenditure (MET), and Charlson index. Physical activity was evaluated with the International Physical Activity Questionnaire. RESULTS: Vitamin D deficiency (<20 ng/mL) was observed in 56% and severe vitamin D deficiency (<10 ng/mL) in 13% of those individuals. Serum concentrations of 25(OH)D were significantly and positively associated with BMD total hip (p = 0.001), femoral neck (p = 0.011) and 33% radius (p = 0.046) BMDs, MET (p = 0.03) and functional reach test (p = 0.037) and negatively with age (p = 0.021), PTH (p = 0.004) and osteoporosis diagnosis (p = 0.012). Long-lived individuals with 25(OH)D ≥ 20 ng/mL had higher total hip and femoral neck BMDs (p = 0.012 and p = 0.014, respectively) and lower PTH (p = 0.030). In multiple linear regression analysis, age and osteoporosis diagnosis remained negatively associated with 25(OH)D levels (p = 0.021 and p = 0.001, respectively), while corrected calcium and cholecalciferol use remained positively associated (p = 0.001 and p = 0.024, respectively). CONCLUSION: We observed high vitamin D inadequacy prevalence in those Brazilian community dwellers' oldest old. Serum concentrations of 25(OH)D were positively associated with bone mass and dynamic balance, and negatively with PTH and osteoporosis diagnosis. Additionally, 25(OH)D ≥ 20 ng/mL was associated with better bone mass and lower PTH levels.

Rare Association Between Osteogenesis Imperfecta and Chondrosarcoma: Could a Pathogenic Variant in the Gene SERPINF1 Explain It?

Osteogenesis imperfecta (OI) type VI is a rare inherited disorder of the connective tissue caused by pathogenic variants in SERPINF1 gene, which encodes the pigment epithelium-derived factor (PEDF). PEDF is implicated in many biologic processes, including an anti-cancer role. This information is supported by in vitro and in vivo studies that evidenced its anti-angiogenic, anti-tumorigenic, and anti-metastatic properties. Although OI is related to skeletal changes such as bone fragility and deformities, as well as to other connective tissue defects, it does not represent a greater predisposition to the development of skeletal tumors. Here, we report on an adult with OI in which a deletion in exon 8 of the SERPINF1 gene (c.1152_1170del; p.384_390del) was identified. The patient presented popcorn calcification in both femoral epiphyses, but one of them presented radiological characteristics and evolution suspected of malignancy. Later, it was diagnosed as chondrosarcoma. This paper discusses that OI type VI patients may be at risk of developing some types of cancer.

Concentrations of total, bioavailable, and free 25OHD in individuals with and without primary hyperparathyroidism and their correlations to DXA and trabecular bone score

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.

Hypophosphatasia: from birth to adulthood

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.

Epidemiology of Vitamin D (EpiVida)-A Study of Vitamin D Status Among Healthy Adults in Brazil.

Context: There are few studies of 25-hydroxyvitamin D (25(OH)D) concentrations in healthy adults in Brazil. Objective: This work aimed to estimate the prevalence of vitamin D status and its association with lifestyle, sociodemographic, and anthropometric data in 3 regions of Brazil. Methods: A cross-sectional study was conducted among blood donors of both sexes, living in the cities of Salvador, São Paulo, and Curitiba during summer. Blood samples were collected during the procedure. Serum 25(OH)D and parathyroid hormone (PTH) were measured in the same laboratory using chemiluminescence immunoassays. Lifestyle, sociodemographic, and anthropometric data were gathered by an interview with a standardized questionnaire. Vitamin D deficiency and insufficiency was defined as 25(OH)D levels below 20 ng/mL and below 30 ng/mL, respectively. Results: A total of 1004 healthy adults were evaluated with mean levels of 25(OH)D (28.7 ± 9.27 ng/mL) and PTH (34.4 ± 15.1 pg/mL). The standardized prevalence of vitamin D deficiency and insufficiency was in the study population 15.3% and 50.9%: in Salvador 12.1% and 47.6%, in São Paulo 20.5%, and 52.4% and in Curitiba 12.7% and 52.1%, (P = .0004). PTH levels were negatively correlated with 25(OH)D levels. Greater body mass index (BMI) and higher latitude were significant predictors of vitamin D deficiency, whereas skin color (White), longer duration of sun exposure, and current use of dietary supplement were protective. Conclusion: This study confirmed the high prevalence of vitamin D deficiency and insufficiency even in the midsummer in a healthy population of Brazil. Vitamin D levels are associated with sun exposure, latitude, BMI, skin color, and use of supplements.

Evidence based Latin American Guidelines of clinical practice on prevention, diagnosis, management and treatment of glucocorticoid induced osteoporosis. A 2022 update : This manuscript has been produced under the auspices of the Committee of National Societies (CNS) and the Committee of Scientific Advisors (CSA) of the International Osteoporosis Foundation (IOF).

Guidelines and recommendations developed and endorsed by the International Osteoporosis Foundation (IOF) are intended to provide guidance for particular pattern of practice for physicians who usually prescribe glucocorticoid (GC) therapy, and not to dictate the care of a particular patient. Adherence to the recommendations within this guideline is voluntary and the ultimate determination regarding their application should be made by the physician in light of each patient's circumstances. Guidelines and recommendations are intended to promote a desirable outcome but cannot guarantee any specific outcome. This guideline and its recommendations are not intended to dictate payment, reimbursement or insurance decisions. Guidelines and recommendations are subjected to periodic revisions as a consequence of the evolution of medicine, technology and clinical practice. A panel of Latin American (LATAM) experts specialized in osteoporosis with recognized clinical experience in managing patients with glucocorticoid-induced osteoporosis (GIO) met to produce evidence-based LATAM recommendations for the diagnosis and management of GIO. These guidelines are particularly intended to general practitioners and primary care physicians who prescribe GC treatments in LATAM to guide their daily clinical practice in terms of evaluation, prevention and treatment of GIO. These recommendations were based on systematic literature review using MEDLINE, EMBASE, SCOPUS and COCHRANE Library database during the period from 2012 to 2021. Randomized clinical trials (RCT), systematic reviews of RCT, controlled observational studies, guidelines and consensus were considered. Based on the review and expert opinion the panel members voted recommendations during two successive rounds of voting by panel members. Agreements for each statement were considered if a concordance of at least 70% was achieved following Delphi methodology. Grading of recommendations was made according to the Oxford Centre for the Evidence-based Medicine (EBM) criteria. Among five GIO guidelines and consensus initially identified, two of them (American College of Rheumatology 2017 and the Brazilian Guidelines 2021) were selected for comparison considering the latter as the most current guides in the LATAM region. Based on this methodology fifty statements were issued. All of them but four (1.20, 1.21, 1.23 and 4.2) attained agreement.

Vitamin D metabolism and extraskeletal outcomes: an update.

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.

Vitamin D metabolism and extraskeletal outcomes: an update

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.

An updated hip fracture incidence rate for Brazil: the Brazilian Validation Osteoporosis Study (BRAVOS).

Hip fracture incidence rates in three representative geographic areas in Brazil over a period of 2 years (2010-2012) were assessed for the first time. Estimated incidence rates varied regionally, and markedly differed from those previously reported. Thus, national guidelines as well as FRAX Brazil should be revised in light of this new data. PURPOSE: To determine the annual incidence of hip fractures in individuals aged 50 years and over, living in 3 cities located in different regions of the country. To investigate the age, gender, and regional differences in fracture rates. Based on the obtained data, to estimate the national incidence of hip fractures resulting from osteoporosis, in order to improve prevention strategies. METHODS: Retrospective, observational study including all patients aged ≥ 50 years admitted in hospitals because of a hip fracture in three cities (Belem, Joinville, and Vitoria) from representative geographic areas in Brazil from 2010 to 2012. Data were obtained from medical records in those cities. We analyzed incidence rates (crude and age- and gender-standardized rates) for hip fractures. RESULTS: There were 1025 (310 in men and 715 in women) hip fractures in the over 50-year-old merged population from the three cities. The crude incidence rate for hip fracture was 103.3/100,000 (95% confidence interval [CI = 97.0; 109.7), in men 77.4/100,000 (95% CI = 68.8; 86.0), and in women 125.2/100,000 (95% CI = 116.0; 134.4). Incidence standardized for age and gender was 105.9 cases per 100,000 persons per year (95% CI = 99.4; 112.4); 78.5 cases per 100,000 (95% CI = 69.8; 87.3) in men and 130.6 cases 100,000 in women (95% CI = 121.0, 140.2) per year. Belem, located in the equatorial region (latitude 1° 27' S), had significantly lower crude and age-adjusted incidence than Joinville (latitude 26° 18' S) and Vitoria (latitude 20° 19' S), which were no different from each other. The incidence of fractures increased exponentially with age, and women had about twice the risk of fractures than men. CONCLUSIONS: Hip fracture mainly affects elderly women and presents great variability in incidence between the different regions in Brazil. The incidence of hip fractures in Brazil differed markedly from that reported previously, so that national guidelines and the FRAX model for Brazil should be revised.

FGF23 levels as a marker of physical performance and falls in community-dwelling very old individuals

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.