Обследовано 116 женщин в постменопаузе. Установлено неравномерное распределение генотипов полиморфизма rs1801197 гена CALCR в группах здоровых женщин, пациентов с остеопорозом и остеопенией (р=0,036). Среди женщин с остеопорозом и остеопенией по сравнению со здоровыми лицами значительно чаще регистрируется аллель С (p<0,001). We examined 116 postmenopausal women. An uneven distribution of the rs1801197 polymorphism genotypes of the CALCR gene was found in the groups of healthy women, patients with osteoporosis and osteopenia (p = 0.036). Among women with osteoporosis and osteopenia, compared with healthy individuals, the C allele is significantly more often recorded (p <0.001).
The role of VDR gene BsmI (rs1544410) and FokI (rs10735810) polymorphisms in postmenopausal osteoporosis formation has been confirmed by the results of fairly large number of studies. However, pharmacogenetic aspects of above polymorphisms have not been adequately studied. The aim of this work is to study the serum levels of certain biochemical parameters, bone turnover markers, vitamin D and parathyroid hormone in women with postmenopausal osteoporosis in the dynamics of treatment by ibandronic acid, depending on VDR gene rs1544410 and rs10735810 polymorphisms. We examined 117 women in dynamics of postmenopausal osteoporosis treatment. The 12-month course therapy included ibandronic acid, calcium and cholecalciferol according to the standard regimen. Detection of genetic polymorphisms was carried out by polymerase chain reaction method in real time. Twice, before the therapy start and at the end of one, the basic biochemical parameters, as well as β-Crosslaps, osteocalcin, 25(OH) D and parathyroid hormone were studied in women blood serum. Women with postmenopausal osteoporosis in treatment dynamics are characterized by significant decrease in serum β-CrossLaps, osteocalcin and alkaline phosphatase (p<0.01), as well as an increase in 25(OH)D concentrations (p<0.01). Prior to the initiation of therapy, GG genotype of the rs10735810 polymorphism of the VDR gene was associated with lower osteocalcin concentrations than in AA genotype (p<0.01). Holders of GG genotype of VDR gene rs1544410 polymorphism, in comparison with other women, are characterized (p<0.01) by lower levels of alkaline phosphatase (before treatment) and calcium (before and after treatment), higher levels of parathyroid hormone (before and after treatment). The obtained results can be used to develop personalized antiresorptive therapy regimens in postmenopausal osteoporosis.
Цель работы – исследовать сывороточные уровни маркера резорбции костной ткани (β-Crosslaps), маркеров остеогенеза (остеокальцин, щелочная фосфатаза), а также кальция, 25-гидроксивитамина D (25(ОН)d) и паратгормона в динамике лечения женщин с постменопаузальным ОП препаратом ибандроновой кислоты. Материал и методы. Обследовано 117 женщин с постменопаузальным остеопорозом в динамике лечения. Контрольную группу составили 75 практически здоровых женщин в постменопаузе. Женщины с остеопорозом были обследованы до и по окончании 12 месячного курса лечения, включавшего прием ибандроната, кальция и холекальциферола в стандартных дозах. В динамике лечения оценивались показатели прироста минеральной плотности кости и изменения вышеуказанных сывороточных факторов. Результаты. Установлено, что пациенты с постменопаузальным остеопорозом по сравнению со здоровыми женщинами характеризуются более низкими значениями веса и индекса массы тела (р<0,001), увеличенной активностью щелочной фосфатазы (р<0,01), повышенными концентрациями в сыворотке крови β-CrossLaps и остеокальцина (р<0,01). Прирост минеральной плотности кости в ответ на 12 месячный курс терапии у женщин с постменопаузальным ОП составил от 2,71±0,53% в зоне шейки левого бедра до 4,55±0,51% в поясничных позвонках L1-L4 (р<0,001). Терапия женщин с постменопаузальным остеопорозом сопровождалась снижением до значений контрольной группы показателей щелочной фосфатазы, β-CrossLaps и остеокальцина (р<0,01), а также уменьшением удельного веса среди них дефицитных по витамину D пациентов (от 60,7% до 20,2%; р<0,001). Заключение. Полученные результаты необходимо использовать как для ранней диагностики постменопаузального остеопороза, так и при лечении женщин с вышеуказанным заболеванием. Ключевые слова: постменопаузальный остеопороз, лечение, костные маркеры, витамин D, паратгормон.
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
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