GynecologyGynecology2079-56962079-5831Consilium Medicum4387010.26442/20795696.2020.4.200188Research ArticlePotential predictive marker of treatment effectiveness in patients with osteopenic syndrome after surgical menopauseZaydievaYansiiat Z.<p>D. Sci. (Med.), Prof., Moscow Regional Research Institute of Obstetrics and Gynecology</p>7726101@rambler.ruhttps://orcid.org/0000-0003-4911-719XKruchininaElena V.<p>Cand. Sci. (Med.), Moscow Regional Research Institute of Obstetrics and Gynecology</p>kruchinina.elena@mail.ruhttps://orcid.org/0000-0002-3628-0863GorenkovaOlga S.<p>Cand. Sci. (Med.), Moscow Regional Research Institute of Obstetrics and Gynecology</p>olga-gore@mail.ruhttps://orcid.org/0000-0002-4448-5877PolyakovaElena Yu.<p>Cand. Sci. (Med.), Vladimirskiy Moscow Regional Research Clinical Institute</p>polyakova_eu@mail.ruhttps://orcid.org/0000-0002-1389-0271KarevaElena N.<p>D. Sci. (Med.), Prof., Sechenov First Moscow State Medical University (Sechenov University)</p>elenakareva@mail.ruKurguzovaDaria O.<p>Assistant, Sechenov First Moscow State Medical University (Sechenov University)</p>kurguzova@mail.ruhttps://orcid.org/0000-0003-1759-5592KochinaNatalya A.<p>Senior Research Officer, Pirogov Russian National Research Medical University</p>natalyakochina@yandex.ruhttps://orcid.org/0000-0001-7748-0071KrasnoshchokKatherine V.<p>biochemist, Pirogov Russian National Research Medical University</p>katherinekamagina@gmail.comhttps://orcid.org/0000-0003-3538-1977SerebrovaSvetlana Yu.<p>D. Sci. (Med.), Prof., Scientific Center for Expertise of Medical Products</p>svetaserebrova@mail.ruhttps://orcid.org/0000-0002-7163-7119Moscow Regional Research Institute of Obstetrics and GynecologyVladimirskiy Moscow Regional Research Clinical InstituteSechenov First Moscow State Medical University (Sechenov University)Pirogov Russian National Research Medical UniversityScientific Center for Expertise of Medical Products10092020224394209092020Copyright © 2020, Consilium Medicum2020<p><strong>Introduction.</strong> Patients with surgical menopause have a risk for osteopenic syndrome (OS). Menopausal hormone therapy (MHT) in combination with calcium and vitamin D promotes increase in bone mineral density (BMD). The expression level of vitamin D receptor in mononuclear fraction cells (MNFC) of blood can be considered as a predictive marker of effectiveness of OS therapy.</p>
<p><strong>Aim. </strong>To search a molecular predictive marker of the effectiveness of OS treatment.</p>
<p><strong>Materials and methods. </strong>The study included 100 women aged 4055 years with a duration of surgical menopause from 12 months to 6 years. The criterion for including patients in the study was the absence of contraindications to the use of MHT. The subject of the study was the determination of BMD by dual-energy X-ray absorptiometry, polymerase chain reaction diagnostics of the level of expression of vitamin D genes, estradiol and progesterone receptors, determination of 25-OH vitamin D in the blood.</p>
<p><strong>Results.</strong> Analysis of 12-month OS therapy effectiveness evaluated with a surrogate marker BMD. The increase in BMD up to 34% per year was treated as absence of negative dynamics, more than 4% per year as positive one. Significant effect of combination therapy compared with MHT on BMD in patients with surgical menopause with a low baseline level of BMD (due to hypovitaminosis D) is associated with the anti-inflammatory, bone-protective effect of vitamin D. In both groups of patients not responding; to the prescribed therapy we were able to conduct a comparative analysis of expression level of the target molecules in the MNFC before the start of treatment. The efficacy of MHT and combination therapy for BMD disorders is positively associated with the expression level of vitamin D receptors in MNFC before treatment. Therefore, the vitDR mRNA level is a potential predictive marker of the effectiveness of OS treatment. The expression levels of nuclear estradiol beta receptor and membrane receptor for progesterone in MNFC before treatment showed an upward trend in women responding to therapy.</p>
<p><strong>Conclusion. </strong>The expression level of the vitamin D receptor in MNFC of blood is significantly lower in the group of women with no/insufficient effect on 12-month combined therapy. This indicator can be considered as a predictive marker of the effectiveness of OS therapy.</p>osteopenic syndromereceptors expressionmononuclear fraction cellsmenopausal hormone therapycalciumvitamin Dостеопенический синдромэкспрессия рецепторовмононуклеарная фракция клетокменопаузальная гормональная терапияпрепараты кальция и витамина D[Francis RM. Non-response to osteoporosis treatment. J Br Menopause Soc 2004; 10 (2): 76–80.][Cesareo R, Falchetti A, Attanasio R et al. Hypovitaminosis D: Is It Time to Consider the Use of Calcifediol? Nutrients 2019; 11: 1016. DOI: 10.3390/nu11051016][Клинические рекомендации Российского общества акушеров-гинекологов, утвержденные информационным письмом Минздрава России от 02.10.2015 №15-4/10/2-5804 «Менопаузальная гормонотерапия и сохранение здоровья женщин в зрелом возрасте». М., 2015. http://www.consultant.ru/document/cons_doc_LAW_320073/ [Klinicheskie rekomendatsii Rossiiskogo obshchestva akusherov-ginekologov, utverzhdennye informatsionnym pis’mom Minzdrava Rossii ot 02.10.2015 №15-4/10/2-5804 «Menopauzal’naia gormonoterapiia i sokhranenie zdorov’ia zhenshchin v zrelom vozraste». Moscow, 2015. http://www.consultant.ru/document/cons_doc_LAW_320073/ (in Russian).]][Boyum A. Separation of leukocytes from blood and bone marrow. Scand J Lab Investig 1968; 21 (97): 1–9.][Cesareo R, Iozzino M, D’Onofrio L et al. Effectiveness and safety of calcium and vitamin D treatment for postmenopausal osteoporosis. Minerva Еndocrinol 2015; 40: 231–7. https://www.researchgate.net/publication/280327589][Kerschan-Schindl K. Prevention and rehabilitation of osteoporosis. Wien Med Wochenschr 2016; 166 (1–2): 22–7. DOI: 10.1007/s10354-015-0417-y][Paschalisa EP, Gamsjaegera S, Hasslera N et al. Vitamin D and calcium supplementation for three years in postmenopausal osteoporosis significantly alters bone mineral and organic matrix quality. Bone 2017; 95: 41–6. DOI: 10.1016/j.bone.2016.11.002][Siddique N, Fallon N, Steen G et al. Treatment of osteoporosis with recombinant parathyroid hormone, utilisation of total body DXA to observe treatment effects on total body composition and factors determining response to therapy. Ir J Med Sci 2019; 188 (2): 505–15. DOI: 10.1007/s11845-018-1875-1]