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The SPAH study is a population-based prospective cohort of Brazilian community-dwelling elderlies with higher fracture risk than observed in the studies used to construct the Brazilian FRAX model. In this study, the FRAX tool was a good fracture predictor within this high-risk elderly cohort, especially when calculated without bone density. PURPOSE: To determine the performances of FRAX and age-dependent intervention thresholds according to National Osteoporosis Guideline Group (NOGG) guidelines with and without bone mineral density (BMD) regarding fracture prediction in community-dwelling elderly Brazilians. METHODS: Seven hundred and five older adults (447 women; 258 men) were followed for 4.3 ± 0.8 years. FRAX risk for hip and major osteoporotic fractures with and without BMD was calculated at baseline. The bivariate analysis investigated the associations between the absolute probability of fracture (FRAX), as well as the age-dependent intervention thresholds (NOGG), and the incidence of vertebral fracture (VF), non-vertebral fracture (NVF), and major osteoporotic fractures (MOF), segregated by sex. Age-adjusted Poisson's multiple regression and ROC curves were constructed to determine FRAX and NOGG's accuracies as fracture predictors. RESULTS: Fractures occurred in 22% of women and 15% of men. FRAX with and without BMD was higher in women with all types of fractures (p < 0.001). Only NOGG risk classification without BMD was associated with NVF (p = 0.047) and MOF (p = 0.024). FRAX was associated with NVF in the multiple regression, regardless of BMD. ROC curves of FRAX with and without BMD had AUCs of 0.74, 0.64, and 0.61 for NVF, VF, and MOF, respectively. The most accurate risk cutoffs for FRAX were 8% for MOF and 3% for hip fractures. No statistically significant associations were found in men. CONCLUSION: FRAX predicted NVF more accurately than VF or MOF in elderlies, regardless of BMD. These results reiterate that FRAX may be used without BMD, even considering that Brazilian elderlies have known higher fracture risk.

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Defective KLOTHO gene expression in mice led to a syndrome resembling human ageing. This study evaluated three KLOTHO polymorphisms, namely G395A, C1818T, and C370S, in an elderly population (mean age of 73 years) and their associations with ageing-related outcomes (cardiovascular events, kidney function, osteoporosis, sarcopenia) and mortality. Estimated glomerular filtration rates (eGFR) was lower in subjects with 1818TT (P = 0.047) and 370SS (P = 0.046) genotypes. The 1818TT genotype (P = 0.006) and 1818T allele were associated with higher frequency of myocardial infarction (MI) (CC:1.7% vs. CT + TT:7.0%; P = 0.002). The 370SS genotype was associated with lower stroke frequency (P = 0.001). MI (OR 3.35 [95% CI: 1.29-8.74]) and stroke (OR 3.64 [95% CI: 1.48-8.97]) were associated with mortality. Regarding MI, logistic regression showed 1818T allele was a risk factor for death-related MI (OR 4.29 [95% CI: 1.60-11.52]; P = 0.003), while 370C was protective (OR 0.03 [95% CI: 0.01-0.08]; P < 0.001). Regarding stroke, the 395A and 370C alleles were protective factors (respectively: OR 0.28 [95% CI: 0.20-0.80]; P = 0.018; OR 0.10 [95% CI: 0.05-0.18]; P < 0.001). This is the first study to determine potential associations between common ageing-related outcomes/mortality and KLOTHO polymorphisms. The 1818T allele was a risk factor for MI-related death. The 395A and 370C alleles were protective factors for stroke-related death in elderly from community.

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RATIONALE: Hypophosphatasia is an inborn error of metabolism that can appear any time in life, mainly with bone manifestations due to low alkaline phosphatase activity. Asfotase alfa is a specific enzyme reposition treatment that has shown promising results in children; however, there are few reports about the outcomes in adult patients. PATIENT CONCERNS: A 36-year-old male presented with an early history of craniosynostosis, short stature, and multiple fractures since the age of 13 years-which needed numerous surgical corrections. He was admitted with a previous diagnosis of osteogenesis imperfecta, taking alendronate, calcium carbonate, cholecalciferol, and calcitriol. Bone mineral density was low (lumbar spine Z-score = -3.0 SD), with impairment of all parameters of high-resolution peripheral quantitative computed tomography (HR-pQCT). Kidney impairment was also observed with reduced creatinine clearance, nephrolithiasis, and nephrocalcinosis. DIAGNOSIS: Alkaline phosphatase was unexpectedly low (6 U/L, reference value: 30-120 U/L), with high serum vitamin B6 (260 mcg/L, reference value: 5.2-34.1). Genetic testing showed a homozygous missense mutation in ALPL gene c.443 C>T: p.Thr148Ile. INTERVENTION: Asfotase alfa was requested due to important bone deterioration, ambulatory disability, and kidney impairment. It was given subcutaneously 2 mg/kg per dose, 3 times a week, for 12 months before reassessment. OUTCOMES: Bone mineral densities of the lumbar spine and whole body, besides almost all HR-pQCT microstructural parameters of the distal tibia, showed improvements and the patient was able to walk without assistant device. Kidney function did not further deteriorate. LESSONS: Hypophosphatasia should be considered as a differential diagnosis in young patients with multiple fractures and kidney impairment, since the use of antiresorptive drugs, calcium and vitamin D, commonly used to treat fractures, worsen its symptoms and prognosis. A 12-month asfotase alfa treatment improved bone density and structural parameters even in an adult patient with late diagnosis.

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BACKGROUND: Vitamin D serum levels and the presence and activity of rheumatic conditions have been associated. However, many studies are merely observational, and the existent randomized clinical trials were never systematically analyzed. Therefore, this study aims to provide a systematic review and meta-analysis of such a topic. METHODS: MEDLINE, EMBASE, LILACS, COCHRANE, and CINAHL were explored to identify randomized trials that investigated clinical repercussions of vitamin D (or analogs) supplementation for at least 3 months in rheumatic diseases. Standardized clinical and/or laboratorial outcomes related to disease activity were analyzed according to each disease before and after supplementation. RESULTS: Database searches rendered 668 results; 9 were included-5 on rheumatoid arthritis, 3 on systemic lupus erythematosus, and 1 on systemic sclerosis. Seven of the studies were meta-analyzed. After vitamin D supplementation, rheumatoid arthritis recurrence decreased; however, not significantly (risk difference = -0.10, 95% CI = -0.21, 0.00, P = .05). No statistical significance was observed regarding visual analog scale (mean difference = 2.79, 95% CI = -1.87, 7.44, P = .24) and disease activity score28 (mean difference = -0.31, 95% CI = -0.86, 0.25, P = .28). Regarding systemic lupus erythematosus, anti-dsDNA positivity was significantly reduced (risk difference = -0.10, 95% CI = -0.18, -0.03; P = .005). CONCLUSION: Vitamin D supplementation reduced anti-dsDNA positivity on systemic lupus erythematosus and could possibly reduce rheumatoid arthritis recurrence, although novel randomized clinical trials are needed to confirm and extend the benefits of this hormone in immune-mediated rheumatic diseases.

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