Исто рия открытия и исследований свойств витамина D (VD) связана с изучением этиологии, патогенеза рахита, а впоследствии и других заболеваний скелета, а также с поиском лечебно-профилактических средств для предупреждения и лечения патологии костной ткани. Краткое клиническое описание рахита было сделано Daniel Whistler еще в 1645 году, а несколько позже, в 1650 году, более полную и детальную картину данного заболевания представил Francis Glisson [6]. Понадобилось более 250 лет, прежде чем была расшифрована этиология рахита. Лишь в начале ХХ века благодаря исследованиям таких ученых, как Е.
The aim of study was to assess torasemide and indapamide effects on magnesium (Mg), potassium (K), calcium (Ca), and sodium (Na) excretion in postmenopausal women with hypertension and heart failure with preserved ejection fraction (HFpEF) depending on Mg exchange. Material and methods. 140 postmenopausal women with hypertension and HFpEF were examined. Based on Mg-tolerance test results, patients were divided into 2 groups: with (n = 72) and without Mg deficiency (n = 68) with randomization into 4 subgroups: 1a, 1b – 36 patients and 2a, 2b - 34 women in each. Subgroups 1a and 2a received torasemide 5 mg, 1b and 2b – indapamide 2.5 mg. Daily diuresis, Na, K, Ca and Mg excretion were determined before and after diuretics use. Results. Diuretics caused equal (p>0.05) increase (p<0.001) in daily urine output and natriuresis by 561 (95%CI: 556–571) ml and 71.0 (95%CI: 68.9– 73.1) mmol/24h. K excretion increased (p<0.0001) only with indapamide use by 21.1 (95% CI: 18.4-23.8) mmol / 24h and 22.3 (95% CI: 19.5-25.0) mmol / 24h in groups 1b and 2b. Mg excretion increase was not detected (p>0.05) only in patients with Mg deficiency torasemide subgroup, but Ca loss remained unchanged (p>0.05) in indapamide subgroups. K/Na and Ca/Na ratio decreased in all groups, while Mg/Na increased with indapamide use and decreased with torasemide use. Torasemide decreased (p<0.001) Mg/Ca excretion ratio, but indapamide decreased (p<0,0001) the one. Conclusion. Indapamide caused significant increase in K, Mg excretion and Mg/Ca, while torasemide increased Ca loss, decreased Mg/Ca, and did not affect K loss in postmenopausal women with hypertension, HFpEF regardless to Mg deficiency. Torasemide did not lead to Mg losses increase in macronutrient-deficiency patients.
Objective: study of associations between VDR gene rs1544410 and rs10735810 polymorphisms, MCM6 gene rs4988235, CALCR gene rs1801197 one and ibandronate efficacy in women with postmenopausal osteoporosis.Materials and methods: 117 women with postmenopausal osteoporosis were examined for 12 months in the dynamics of treatment with ibandronate. Evaluation of therapy effectiveness was based on indicators of increase in bone mineral density in L1-L4 lumbar vertebrae, as well as left and right femurs.Results: An association of GG genotype of VDR gene rs1544410 polymorphism with low growth rates of mineral density of L1-L4 lumbar vertebrae (3,41 ± 0,60 % versus 5,51 ± 0,78 % in other women; р = 0,036) was established. The effect of other studied polymorphisms (rs10735810 of VDR gene, rs4988235 of MCM6 gene, rs1801197 of CALCR gene) on treatment effectiveness was not found.Conclusion: it is advisable to use obtained results when developing personalized regimens for antiresorptive therapy for women with postmenopausal osteoporosis.
An assessment of genetic factors influence on ibandronic acid effect in postmenopausal osteoporosis treatment can significantly bring us closer to the practical use of this results in prognostic genetics and personalized medicine. The aim was the study of associations between 283 A>G (BsmI, rs1544410) polymorphisms of vitamin D receptor gene (VDR) and ibandronic acid efficacy in postmenopausal osteoporosis treatment. 117 women with postmenopausal osteoporosis were examined through treatment dynamics. A 12-month therapy course included the use of ibandronic acid according to standard regimen. Evaluation of treatment effectiveness was carried out by changes (%) in bone mineral density (BMD) separately for each area by dual- energy X-ray absorptiometry. Real-time PCR was used to determine VDR gene rs1544410 polymorphism. It was found that for 12 months ibandronate use caused significant (p<0.001) BMD increase. BMD increase ranged from 2.71±0.53% in left femoral neck zone to 4.63±0.53% in the L1-L4 lumbar vertebrae. The treatment outcome did not depend (p>0.05) on age, height, weight, body mass index, and postmenopause duration. GG genotype of rs1544410 polymorphism was associated with lower BMD growth rate in L1-L4 lumbar vertebrae (p=0.036). Screening of women with postmenopausal osteoporosis for polymorphic variants of VDR gene (rs1544410) before antiresorptive therapy with ibandronic acid may be appropriate to predict the effect and individualize treatment and prophylactic measures. The obtained results can contribute to more complete understanding of osteoporosis pharmacogenetics
Цель исследования – изучить клинико-анамнестические данные, особенности образа жизни, питания женщин постменопаузального возраста, имеющих остеопороз. Материал и методы. Обследовано 278 женщин постменопаузального возраста. Показатели костной ткани поясничных позвонков L1-L4, проксимальных отделов и шеек левой и правой бедренных костей устанавливали методом двухэнергетической рентгеновской абсорбциометрии. У женщин определяли антропометрические характеристики, выясняли анамнестические данные в фертильном и постменопаузальном возрасте, пищевой рацион, вредные привычки, изучали основные клинические признаки остеопороза. При статистической обработке данных вычисляли медиану (Ме) и интерквартильный размах (Q1-Q3), коэффициент ранговой корреляции Спирмена (rs), использовали ранговый однофакторный анализ Крускала-Уоллиса и критерий Данна. Результаты. Установлено, что женщины с остеопенией и остеопорозом по сравнению с контрольной группой имеют существенно сниженные показатели роста, веса и индекса массы тела (р<0,05 – р<0,01). Показатели минеральной плотности шейки и всего проксимального отдела левого бедра, шейки правого бедра имеют обратные корреляционные связи (rs=-0,23 – rs=-0,29) с возрастом обследованных лиц и длительностью постменопаузального периода (р<0,05). Кроме того, обнаружены корреляции (р<0,05) возраста и длительности постменопаузы с минеральной плотностью соответственно поясничных позвонков L1-L4 (rs=-0,13) и всего проксимального отдела правого бедра (rs=-0,19). Наряду с вышеизложенным, постменопаузальный остеопороз характеризуется сниженными показателями возраста менархе, длительности менструального цикла, сексуальной активности, времени пребывания на солнце, уровня потребления молочных сыров и творога (р<0,05). Женщины с остеопорозом отличаются повышенным количеством низкоэнергетических переломов, динамикой снижения роста и выраженным болевым синдромом в грудном и поясничном отделе позвоночника (р<0,05). Заключение. Полученные данные целесообразно использовать для определения прогноза и ранней диагностики постменопаузального остеопороза, при назначении лечебно-профилактических мероприятий.
The aim of study was to identify markers of bone turnover such as osteoprotegerin (OPG), receptor activator for nuclear factor kappa-B ligand (RANKL), 25-hydroxyvitamin D (25(OH)D), and bone density (BMD) in postmenopausal women with arterial hypertension (AH) and heart failure with preserved ejection fraction (HFpEF), depending on magnesium (Mg) status. Material and methods. 140 postmenopausal women aged 52 to 76 years with AH and HFpEF were examined. Based on the Mg-tolerance test, patients were divided into 2 groups: with Mg deficiency (n=72) and without one (n=68). BMD in the neck and proximal femoral area, as well as L1-L4 vertebrae, was measured in by dual-energy X-ray absorptiometry. OPG, soluble RANKL (sRANKL) and 25(OH)D level was also determined by enzyme immunoassay. Results. In Mg deficiency group were noted lower BMD indices in L1-L4 vertebrae area (0,990±0,159 g/cm2 vs 1,046±0,193 g/cm2; p=0,041) and higher osteopenia incidence (RR=1,60; 95% CI: 1,08–2,38; p=0,019). Also, Mg deficient women had higher level of OPG (85,2 [69,1; 103,1] pg/ml vs 79,9 [63,4; 92,7] pg/ml, p=0,035) and sRANKL (3,98 [2,70; 5,45] pg/ml vs 2,85 [1,95; 3,82] pg/ml, p<0,0001) expression, but lower OPG/sRANKL ratio (22.59 [15.34; 33.71] vs 26.01 [19.42; 41.19], p=0.028) in opposite to control group parameters. At the same time, patients with Mg deficiency had higher 25(OH)D impaired status incidence (97% vs 87%; p=0,028). Conclusion. Lower BMD and OPG/sRANKL ratio, but higher OPG and sRANKL expression and higher frequency of 25(OH)D impaired status were revealed in postmenopausal women with AH, HFpEF and Mg deficiency compared to the control group.
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