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[English] Due to continuous aging of population and increase in the number of elderly people, osteoporosis became socially significant disease leading to disability, increasing mortality and thereby putting an additional burden on the public healthcare system. Screening to identify groups with a high probability of fracture is recommended using the FRAX® Tool for all postmenopausal women and men over 50 years old (А1). In the presense of major pathological fractures (hip, spine, multiple fractures) it is recommended to diagnose osteoporosis and prescribe treatment regardless of the results of spine and hip double X-ray absorptiometry (DXA) or FRAX® (B2). It is recommended to evaluate C-terminal telopeptide when prescribing antiresorptive therapy and procollagen type 1 N-terminal propeptide (P1NP) when prescribing anabolic therapy to patients receiving osteoporosis treatment at baseline and 3 months after the start of therapy in order to assess the effectiveness of treatment early and adherence to the therapy (А2). It is recommended to diagnose osteoporosis and prescribe treatment to patients with high individual 10-year probability of major pathological fractures (FRAX®) regardless of the results of spine and hip DXA (В3). It is recommended to diagnose osteoporosis and prescribe treatment with a decrease in BMD, measured by DXA, by 2.5 or more T-score standard deviations in femoral neck, and/or in total hip, and/or in lumbar vertebrae, in postmenopausal women and men over 50 years old (А2). It is recommended to prescribe bisphosphonates, denosumab or teriparatide to prevent pathological fractures and increase BMD in patients with postmenopausal osteoporosis, osteoporosis in men, glucocorticoid-induced osteoporosis (А2). When the clinical effect of therapy in osteoporotic patients without pathological fractures is achieved (BMD T-score > -2.0 SD in femoral neck and absence of new fractures), it is recommended to interrupt bisphosphonates therapy for 1-2 years with subsequent follow-up (B2). In patients with vertebral fractures, hip fractures or multiple fractures, it is recommended to continue ceaseless long-term treatment of osteoporosis (В3). All drugs for the treatment of osteoporosis are recommended to be prescribed in combination with calcium and cholecalciferol (А2). In order to reduce the risk of recurrent fractures by prescribing osteoporosis therapy timely and maintaining long-term follow-up of patients over 50 years old with pathological fractures, it is recommended to create Fracture Liaison Services (В2). [Русский] В связи с непрерывным старением населения и увеличением количества лиц старшего и пожилого возраста остеопороз стал социально значимым заболеванием, приводя к инвалидности, повышая уровень смертности и создавая тем самым дополнительную нагрузку на систему здравоохранения. Скрининг для выявления групп с высокой вероятностью переломов рекомендован с использованием Алгоритма FRAX® среди всех женщин в постменопаузе и мужчин старше 50 лет (А1). При наличии патологических переломов крупных костей скелета (бедренной кости, тел(а) позвонков(-а), множественных переломов) в анамнезе рекомендовано устанавливать диагноз остеопороза и назначать лечение независимо от результатов рентгеноденситометрии поясничного отдела позвоночника и проксимального отдела бедренной кости или FRAX® (B2). Рекомендуется определение С-концевого телопептида при назначении антирезорбтивной терапии и исследование уровня N-терминального пропептида проколлагена 1-го типа (P1NP) при назначении анаболической терапии пациентам, получающим лечение остеопороза, исходно и через 3 месяца от начала терапии с целью ранней оценки эффективности лечения и приверженности к терапии (А2). Рекомендовано устанавливать диагноз остеопороза и назначать лечение пациентам c высокой индивидуальной 10-летней вероятностью основных патологических переломов (FRAX®) независимо от показателя рентгеноденситометрии поясничного отдела позвоночника и проксимального отдела бедренной кости (В3). Рекомендовано устанавливать диагноз «остеопороз» и назначать терапию при снижении МПК, измеренной при DXA, на 2,5 и более стандартных отклонения по Т-критерию в шейке бедренной кости, и/или в целом в проксимальном отделе бедренной кости, и/или в поясничных позвонках у женщин в постменопаузе и у мужчин старше 50 лет (А2). Для предупреждения патологических переломов и повышения МПК у пациентов с постменопаузальным остеопорозом, остеопорозом у мужчин, глюкокортикоидным остеопорозом рекомендуется прием бисфосфонатов, деносумаба или терипаратида (А2). Пациентам с остеопорозом без патологических переломов при достижении клинического эффекта терапии (МПК до -2,0 SD по Т-критерию в шейке бедренной кости и отсутствие новых переломов) рекомендовано на 1-2 года прекратить терапию бисфосфонатами с последующим динамическим наблюдением (B2). Пациентам с переломами тел позвонков, бедренной кости или множественными переломами в анамнезе рекомендуется продолжать непрерывное длительное лечение остеопороза (В3). Все препараты для лечения остеопороза рекомендуется назначать в сочетании с препаратами кальция и колекальциферола (А2). С целью своевременного назначения терапии остеопороза и обеспечения длительного наблюдения за пациентами в возрасте 50 лет и старше с патологическими переломами для снижения риска повторных переломов рекомендуется создавать Службы профилактики повторных переломов (В2).

In the age of broad medical options, women’s health has received sufficient attention. The different periods of a woman’s life are characterised by specific physiological changes, based on the age-related characteristics of the reproductive system. The onset of menopause can have a negative impact on health in varying degrees. Clinicians have a clear understanding of the effects of estrogen deficiency and the therapeutic options for managing it with menopausal hormone therapy (MHT) and alternative methods of treatment. However, to date, methods for optimising and individualising the correction of menopausal disorders continue to improve. The individualization of MHT is aimed at increasing the efficacy of menopausal management and minimizing possible adverse events. Individualization is based on the selection of a hormone drug taking into account age, menopausal status, somatic health of the woman and her main complaints against the background of estrogen deficiency. The next stage of transformation of MHT concerned the composition of the drugs and the doses of their components. The evolution of the estrogenic component began with the use of conjugated estrogens, whose metabolism is not fully clarified, and stopped at the production of bioidentical estrogens (17p-estradiol and estradiol valerate), which in their structure are as close as possible to ovarian estradiol. The type, dose and combination of estrogens and progestogens determine the severity and specificity of the effect of the hormone. This article will present a clinical case study of the low- and ultra-low-dose combination of 17p-estradiol and dydrogesterone (E/DG).

The history of the discovery of vitamin D (VD) has crossed 100 years. Initially, VD deficiency was limitedly associated with the development of rickets in children. Later, on the basis of a number of studies, it was found that VD deficiency is a risk factor for osteoporosis in men and women. However, the traditional concept of VD as the main regulator of calcium-phosphorus metabolism has undergone dramatic changes over the past two decades. A prerequisite for revising the role of VD and the spectrum of its biological properties was the identification of the distribution of its specific receptors in the body. VD receptors are expressed in the intestine, thyroid and parathyroid glands, kidneys, ovaries, uterus, placenta, hypothalamus, pituitary gland and play a vital function not only in calcium homeostasis. Accordingly, the list of target organs for VD action has been modified. VD deficiency, calculated on a pandemic scale, is a factor that increases the risk of developing not only osteoporosis, but also a number of other diseases. Observational and epidemiological studies have shown that reproductive system disorders are very often combined with VD insufficiency / deficiency. Subsequent scientific research aimed at establishing the role of VD in the formation of a particular pathology of the reproductive system has shown very ambiguous results. VD is recognized as an essential component of maintaining a woman’s reproductive health. Of course, the presence of an established association is not evidence of a causal relationship. There is a need for additional testing. This review focuses on the effect of VD on ovarian function and the formation of various dysfunctional conditions.

In accordance with the data of the Federal Clinical Recommendations for the Diagnosis, Treatment and Prevention of Osteoporosis, with the latter, antiresorptive drugs (denosumab, bisphosphonates) are used, which mainly suppress bone resorption, and anabolic compounds (teriparatide), which enhance bone formation. The vector of their pharmacological effect helps to prevent BMD loss and significantly reduces the risk of low-energy vertebral fractures and fractures of other localizations. The experience of clinical trials makes it possible to successfully carry out antiresorptive therapy with some drugs (denosumab) for up to 10 years, demonstrating good adherence and tolerance. Bisphosphonates remain in the bone matrix for a long time and are characterized by a period of a certain aftereffect. Denosumab and teriparatide show their effect only during the period of direct use. According to some data, when denosumab therapy is canceled in a situation where the targeted goal is achieved, the incidence of vertebral fractures increases, especially in patients with a history of low-traumatic fractures. The article will present the main provisions of the European Calcified Tissues Society, the European Medical Agency, the Russian Association for Osteoporosis regarding the timing of treatment and an analysis of clinical situations requiring the appointment of alternative antiresorptive therapy. According to the resolution of the Council of Experts of the Russian Association on Osteoporosis, bisphosphonates are recommended for all patients to prevent an increased risk of vertebral fractures 6 months after patients had their last subcutaneous injection of denosumab. Oral bisphosphonates should be taken immediately, and zoledronic acid injection should be delayed for another 65 days following a missed denosumab injection.

Aim. To analyze and systematize the available information on pathogenetic mechanisms of hormonal carcinogenesis. Materials and methods. The review includes data from foreign articles published in PubMed and Medline and national works posted on elibrary.ru over the past 20 years. Results. Currently, the term estrogen is often used in the context of hormonal carcinogenesis. According to most researchers, it should not fit into the narrow framework of receptor-mediated proliferation induced by estrogens in target tissues. The concept of estrobiome as a combination of all mechanisms providing the realization of estrogen effects should include not only hormones and native receptors themselves, but also the enzymes involved in their synthesis, estrogen metabolites, intestinal microbiota, as well as genetic and epigenetic factors. Conclusions. When analyzing cancer risk, it is necessary to comprehensively assess contributing factors and hormonal-metabolic preconditions for neoplastic process.

Currently, tamoxifen is the gold standard in the treatment of hormone receptor-positive breast cancer, which reduces recurrent tumor risk by more than 40%. Tamoxifen, which belongs to selective estrogen receptor modulators, can cause endometrial changes in women of different age groups and increase the risk of hyperplasia and endometrial cancer by several times. In clinical practice, the occurrence of various endometrial alterations during tamoxifen treatment often leads to groundless drug withdrawal. Oncology, gynecology and radiology community knowledge related to optimal methods and criteria for diagnosing different tamoxifen-induced endometrial conditions, as well as in choosing the optimal treatment tactics, will be instrumental in the unified and correct approach to managing patients with hormone receptor-positive breast cancer and maintaining tamoxifen therapy due to its high effectiveness.

The aim of the work is to conduct a systematic analysis of the available research results on the possibility of using menopausal hormone therapy (MHT) in patients who successfully completed the treatment of endometrial cancer (EC). Materials and methods. The review includes data from foreign articles published in PubMed and Medline, and domestic works published on elibrary.ru over the past 40 years. Results. The results obtained allow us to consider MHT as an independent method of medical rehabilitation for women who have undergone EC. A clear patient profile should be established, allowing the use of this method, with strict adherence to health monitoring. Conclusion Patients who have successfully completed the treatment of EC require the creation of special rehabilitation conditions in the interests of maintaining health and quality of life and should be under the close attention of the doctor. Argumented approaches to the appointment of MHT in such patients will avoid complications associated with estrogen deficiency after surgery, radiation with or without systemic (cytostatic) treatment methods.

The article presents the basic definitions related to the treatment of postmenopausal osteoporosis, and certain sections from the guidelines of the Russian Association on Osteoporosis (2016) dedicated to the prescription of active vitamin D metabolites (alfacalcidol).

[English] A summary of the draft federal clinical guidelines on osteoporosis developed by members of the Russian Association of Endocrinologists, the Russian Association for Osteoporosis, the Association of Rheumatologists of Russia, the Association of Traumatologists and Orthopedists of Russia, the Russian Association for Menopause and the Russian Association of Gerontologists and Geriatrics is presented. The recommendations were developed from the perspective of evidence-based medicine, in accordance with the requirements for compiling clinical recommendations of the Ministry of Health of Russia published in 2019. A significant place is given to screening of primary osteoporosis in adults, differential diagnosis with other metabolic diseases of the skeleton, modern methods of diagnosing osteoporosis, principles of prescribing pathogenetic treatment, features of sequential and combination therapy, disease prevention and rehabilitation. Clinical recommendations will be useful both to general practitioners and physicians, as well as to narrow specialists, primarily endocrinologists, rheumatologists, orthopedic traumatologists, nephrologists, obstetrician-gynecologists and neurologists, since osteoporosis is a multifactorial and multidisciplinary disease. [Русский] Представлено краткое изложение проекта федеральных клинических рекомендаций по остеопорозу, разработанных членами Российской ассоциации эндокринологов, Российской ассоциации по остеопорозу, Ассоциации ревматологов России, Ассоциации травматологов-ортопедов России, Российской ассоциации по менопаузе и Российской ассоциации геронтологов и гериатров. Рекомендации разработаны с позиций доказательной медицины, в соответствии с требованиями к составлению клинических рекомендаций Минздрава России, опубликованными в 2019 г. Значительное место в изложении отведено скринингу первичного остеопороза у взрослых, дифференциальной диагностике с другими метаболическими заболеваниями скелета, современным методам диагностики остеопороза, принципам назначения патогенетического лечения, особенности последовательной и комбинированной терапии, профилактики заболевания и реабилитации. Клинические рекомендации полезны будут как врачам общей практики и терапевтам, так и узким специалистам, прежде всего эндокринологам, ревматологам, травматологам-ортопедам, нефрологам, акушерам-гинекологам и неврологам, так как остеопороз является мультифакториальным и мультидисциплинарным заболеванием.

The paper presents a review of accumulated data relating to major definitions in diagnostics and therapy of the premenstrual syndrome and own experience represented by case histories. Various therapeutic approaches from the point of view of evidencebased medicine are highlighted.

Aim. To identify gene polymorphisms (OPG, RANKL, VDR, SOST) and evaluate their relationship with bone mineral density (BMD) and fractures for further optimization of diagnosis and treatment of postmenopausal osteoporosis (PMO). Materials and methods. The study included 236 postmenopausal women living in Moscow and the Moscow region. The main group (I) consisted of 174 patients, aged 50 to 83 years, with BMD < - 2.5 SD for the T-score. The comparison group (II) consisted of 62 postmenopausal women with BMD within the normal range and the lack of previous fractures, aged 50 to 77 years. Molecular genetic analysis of polymorphisms of VDR (rs10735810, rs1544410), RANKL (rs9594738, rs9594759) and OPG (rs3102735, rs3102735 and rs4355801), SOST (rs1230399) was performed by polymerase chain reaction in all subjects with PMO and in the control group. Results. In the presence of the T allele of the gene RANKL (rs9594759 and rs9594738) risk of reduced BMD at L1-L4 was increased by 2 times. Women with genotype C/C gene polymorphism of OPG (rs3102735) the risk of fractures of the distal radius (PR) was increased by 17 times, regardless of BMD. Genotype G/G rs1544410 polymorphism of VDR gene in patients with PMO is associated with an increased risk of fractures of the distal radius by three times. In patients with PMO genotype C/C in gene SOST (rs1230399) only cause differences in body mass index. According to an autosomal recessive pattern, homozygous genotype C/C was significantly associated with obesity in the PMO. Conclusions. Polymorphisms of genes RANKL (rs9594759 and rs9594738), OPG (rs3102735) and VDR (rs1544410) are associated with the risk of fractures and PMO. Gene SOST (rs1230399) had no statistically significant effect on BMD and fracture risk.

The paper presents data on the role of vitamin D and calcium in the function of many human organs and tissues. Lifestyle, dietary preferences, and insufficient physical activity contribute to the high prevalence of vitamin D and calcium deficiencies in the adult population of Russia, causing different diseases and abnormalities. The authors have worked out recommendations for the preventive use of vitamin D and calcium in healthy population, give consumption rates for these substances, and describe the clinical and laboratory signs of vitamin D deficiency and indications for screening. They also propose treatment regimens for vitamin D deficiency and depict the signs of intoxication in overdose. Particular emphasis is laid on the place of vitamin D and calcium in the therapy of osteoporosis.

In considering the various aspects of menopause, not enough attention is paid to a significant reduction in the quality of life for women in transition and early postmenopause. Timely administration of menopausal hormone therapy is effective in reducing menopausal symptoms and improves quality of life at a given time, as well as the risk of developing diseases of aging, that can improve the quality of life related to health, and overall well-being of women in the more distant future. The choice of medication should be determined by its composition and clinical characteristics of the particular patient.

Infusions of aminobisphosphonates are now established therapies ofpostmenopausal osteoporosis. Their use is associated with fever and musculoskeletal pain in some subjects, referred to as the acute phase response (APR). The purpose of the study was to explore tolerability of zoledronic acid in the treatment of postmenopausal osteoporosis. In a 36-month open label, prospective study patients with postmenopausal osteoporosis iv received zoledronic acid at a dose of 5 mg every 12 months. We then analyzed the tolerability of the treatment at the hospital and via telephone interviews during the next 14 days and every 3 months after the infusion. Prevention of APR was carried out with paracetamol 500 mg x 3 times a day on the day of first infusion and the next 2 days. Symptoms of APR were recorded in 39% (n=43) of patients with prevention therapy. APR developed in the first 12-24 hours after infusion of zoledronic acid. Among women without prevention APR developed in 65% (n=75) of cases. (OR=0.34 CI (0.2-0.59)). After the 2 nd infusion symptoms of APR were noted in 27.9% (n=26) (р90% of cases the symptoms were of mild or moderate severity, with resolution within 3 days after infusion of zoledronic acid. The most frequent symptoms were bone and muscular manifestations and a flu-like syndrome (p