RESUMEN
CONTEXT: Several trials have reported an increased risk of fractures and falls after intermittent high-dose vitamin D. Treatment with loading doses of vitamin D may increase 1,25(OH)(2) vitamin D catabolism through changes in calcium/phosphate homeostasis and fibroblast growth factor-23 (FGF-23). OBJECTIVE: The aim was to determine the effects of high-dose vitamin D on circulating concentrations of 1,25(OH)(2) vitamin D and FGF-23 in patients with osteoporosis and vitamin D insufficiency. DESIGN, SETTING, PATIENTS, AND INTERVENTION: We carried out a prospective study of 45 subjects with vitamin D deficiency/insufficiency treated with a bolus dose of 300 000 IU of vitamin D(2) im. Blood samples were obtained at baseline and 1, 2, and 3 months after treatment. OUTCOME MEASURES: Changes in 1,25(OH)(2)-vitamin D and FGF-23 were measured. RESULTS: Loading dose of vitamin D(2) increased 1,25(OH)(2)-vitamin D(2) at 3 months, with a mean [SD] of 41 [56] pmol/L at baseline and 162.3 [137.8] pmol/L at 3 months (P < .001). FGF-23 increased significantly at all time points with a peak at 3 months, with percent change from baseline (mean [SEM]) of 50% [48%] at 3 months (P < .01). There was a positive correlation between FGF-23 and serum phosphate (r = 0.36, P = .024) and calcium (r = 0.532, P < .001) and a negative correlation between total 1,25(OH)(2)-vitamin D and FGF-23 (r = -0.32, P = .036) at 3 months. CONCLUSIONS: High-dose vitamin D increases 1,25(OH)(2)-vitamin D and FGF-23 concentration. Further studies are required to determine whether adjusting vitamin D dose and frequency to minimize increases in FGF-23 may prevent the adverse outcomes associated with high-dose intermittent vitamin D supplementation.
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Ergocalciferoles/farmacología , Factores de Crecimiento de Fibroblastos/sangre , Deficiencia de Vitamina D/sangre , Vitamina D/análogos & derivados , Anciano , Alendronato/uso terapéutico , Densidad Ósea , Conservadores de la Densidad Ósea/uso terapéutico , Femenino , Factor-23 de Crecimiento de Fibroblastos , Humanos , Masculino , Persona de Mediana Edad , Osteoporosis/sangre , Posmenopausia/sangre , Vitamina D/sangre , Deficiencia de Vitamina D/tratamiento farmacológicoRESUMEN
OBJECTIVES: The aim of the study was to evaluate fat tissue distribution in HIV-infected patients with suppressed viraemia treated with darunavir/ritonavir (darunavir/r) monotherapy versus darunavir/r triple therapy. METHODS: This study was a substudy of the randomized, multicentre, open-label MONOI-ANRS 136 trial. Body fat distribution and metabolic parameters were measured at baseline, week 48 and week 96. RESULTS: In total, 156 patients of the 225 initially enrolled in the MONOI trial participated in this study, 75 in the darunavir/r monotherapy arm and 81 in the darunavir/r triple-therapy arm. The median limb fat increase from baseline was +0.34 kg [interquartile range (IQR) -0.040 to +1.140 kg; P < 0.001] at week 48 and +0.33 kg (IQR -0.14 to +1.26 kg; P = 0.001) at week 96 in the monotherapy arm, while there was no change (-0.02 kg; IQR -0.53 to +0.52 kg) at week 48 and then an increase of +0.23 kg (IQR -0.45 to +0.87 kg; P = 0.046) at week 96 in the triple-therapy arm. The two arms differed significantly at week 48 (P = 0.001) but not at week 96. The median increase in trunk fat was +0.73 kg (IQR -0.24 to +1.60 kg; P < 0.001) and 0.60 kg (IQR -0.41 to +1.49 kg; P = 0.03) at week 48 and +1.16 kg (IQR -0.17 to +2.75 kg; P < 0.001) and +0.90 kg (IQR -0.51 to +2.34 kg; P = 0.001) at week 96 in the monotherapy and triple-therapy arms, respectively, with no difference between arms. At week 96, the only biological change was a glucose level elevation in the monotherapy arm (median +4.0 mg/dL; IQR -4.0 to +7.0 mg/dL) compared with the triple-therapy arm (P = 0.012). CONCLUSIONS: Overall, body fat tissue increased in patients on darunavir/r monotherapy and triple therapy, with no difference between the arms over 96 weeks. The only difference found was a delayed increase in limb fat tissue in the triple-therapy arm compared with the monotherapy arm in the first year.
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Distribución de la Grasa Corporal , Infecciones por VIH/tratamiento farmacológico , Inhibidores de la Proteasa del VIH/administración & dosificación , Inhibidores de la Proteasa del VIH/efectos adversos , Síndrome de Lipodistrofia Asociada a VIH/inducido químicamente , Inhibidores de la Transcriptasa Inversa/administración & dosificación , Ritonavir/administración & dosificación , Sulfonamidas/administración & dosificación , Adulto , Darunavir , Quimioterapia Combinada/métodos , Femenino , Francia , Infecciones por VIH/fisiopatología , Humanos , Masculino , Persona de Mediana Edad , Inhibidores de la Transcriptasa Inversa/efectos adversos , Ritonavir/efectos adversos , Sulfonamidas/efectos adversosRESUMEN
INTRODUCTION: Systemic lupus erythematosus is still of unknown origin. Viruses have long been postulated to play a role in its pathogenesis particularly cytomegalovirus and Epstein-Barr virus. EXEGESE: We describe three patients who presented acute onset of systémic lupus erythematosus concurrently with recent viral infection (two with cytomegalovirus and one with Epstein-Barr virus). CONCLUSION: The peculiar clinical events emphasize the difficulty of diagnosis at the onset of the disease and suggest possible role of these viruses in the pathogenesis of SLE.