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Phosphaturic mesenchymal tumor can cause osteomalacia due to excessive secretion of fibroblast growth factor 23 (FGF23), which disrupts the metabolism of phosphate and vitamin D. These tumors are predominantly benign, but less than 5% of them are malignant forms. This article presents the first clinical case in the Russian Federation of a 69-year-old patient with severe hypophosphatemia due to metastatic prostate cancer. Increased secretion of FGF23 are described in the androgen-resistent prostate cancer, which led to pronounced disorders of mineral metabolism, accompanied by a clinical symptom of weakness, pain in the bones, immobilization of the patient. The condition was regarded as worsening against the background of the progression of the disease. However, symptomatic therapy aimed at increasing the level of phosphate significantly improved the patient’s general condition. The medical community should be aware of the possibility of developing hypophosphatemia in patients with weakness and bone pain, which are not always associated with the progression of metastatic prostate cancer.

This draft clinical practice guideline for the diagnosis, treatment and prevention of vitamin D deficiency is an update from a previous 2016 document. An analysis of the relevant literature data was carried out, with particular attention to meta-­analyzes, randomized clinical trials and systematic reviews published over the past 5 years. The updated recommendations were discussed and revised by the leading endocrinologists of the Russian Federation, who have expert status in this issue.The classification of 25(OH)D levels has been revised (in particular, the target range of 25(OH)D values has been specified), recommendations have been developed for screening of the disorders associated with vitamin D deficiency. The concept of vitamin D-associated toxicity and recommendations for its diagnosis and prevention have been introduced. Also, indications for the assessment of other vitamin D metabolites besides 25(OH)D, the main marker of vitamin D status, have been indicated.The section regarding treatment of vitamin D deficiency has been expanded and corrected. The major additions concerned the replenishment of the vitamin D deficiency and insufficiency in certain categories of patients (particularly, in the presence of the chronic kidney disease and autoimmune diseases, as well as in pregnant women) and monitoring of the effectiveness and safety of the therapy. The indications for prescribing active metabolites of vitamin D have been adjusted. Recommendations for the prevention of vitamin D deficiency in the general population have also been revised, taking into account large randomized clinical trials, meta-analyzes and systematic reviews of recent years.This publication is an expanded version of the federal guidelines.

McCune Albright syndrome (MAS) is a rare disorder caused by a sporadic postzygotic mutation in the GNAS gene, which encodes the alpha subunit of the Gs signaling protein.Permanent activation of the Gs protein leads to uncontrolled production of intracellular cAMP, and autonomic hyperfunction of target organs. Estimated prevalence of the disease – 1\100000 to 1\1000000. For the first time, MAS syndrome was described in 1936 as a triad of symptoms – fibrous dysplasia of bones (FD), spots on the skin of the color of «coffee with milk» and premature sexual development. However, it is now known, that the phenotype of the disease is much more complex. This is primarily due to the mosaic type of mutation in the GNAS gene, which determines a wide range of clinical manifestations, and presents certain difficulties in the diagnosis of this syndrome. Various endocrinopathies can be manifestations of MAS like an acromegaly, a hyperthyroidism, Cushing’s syndrome, hypophospatemic osteomalacia as well as damage to other organs and systems, namely the pathology of the gastrointestinal tract, hepato-biliary cardiovascular systems. This article presents three late diagnosed clinical cases of MAS in patients with coffee-milk spots and FD, multinodular goiter; in two cases in combination with acromegaly. We have demonstrated the possibilities of drug therapy for acromegaly in MAS, as well as the experience of using bisphosphonate for the treatment of FD.The knowledge of clinical manifestations of the MAS, early diagnostics and possibilities of drug therapy in the management of these patients have the important prognostic value for improving the quality of patient’s life.

[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).

Myokines are hormone-like acting molecules produced in skeletal muscles during and immediately after exercise. They affect both paracrine (inside the muscles themselves) and endocrine manner (in adipose tissue, liver, endothelium, skin, mucosa etc.) implementing different effects on target tissues, mainly through regulation of metabolic processes (such as glucose and lipid metabolism, growth and division of neurons and endothelial cells and others). The examination of myokines is of great interest for researchers of different medicine departments, particularly for endocrinologists, because of myokines’ involvement in pathogenesis of abdominal and visceral obesity, diabetes mellitus type 2 and cardiovascular diseases that are all the components of metabolic syndrome. The most important issue for clinicians is a possibility of future therapeutic implication of the myokine’s signal pathways in treatment of widespread metabolic disorders.

Представлено краткое изложение клинических рекомендаций по диагностике и лечению остеопороза, разработанных членами Российской ассоциации эндокринологов при участии членов Российской ассоциации по остеопорозу (ревматологов, травматологов, терапевтов, гинекологов-эндокринологов). Рекомендации разработаны с позиций доказательной медицины, в соответствии с требованиями к составлению клинических рекомендаций Минздрава России, опубликованными в 2016 г. Значительное место в изложении отведено диагностике остеопороза у взрослых, дифференциальной диагностике с другими метаболическими заболеваниями скелета, а также принципам патогенетического лечения остеопороза. Клинические рекомендации полезны будут как врачам общей практики, так и специалистам, прежде всего эндокринологам, ревматологам, травматологам-ортопедам, гинекологам, нефрологам, гастроэнднрологам и неврологам, так как остеопороз является мультифакториальным и мультидисциплинарным заболеванием

This review discusses the recent evidence showing that the skeleton itself produces at least two hormones: fibroblast growth factor 23 (FGF23) and osteocalcin. FGF23 is secreted by osteocytes in bone and acts on the kidney to inhibit 1-alpha-hydroxilation ofvitamin D and promote phosphorous excretion. The affinity of FGF23 to FGF receptor is low, but FGF23 binds to FGF receptor-Klotho complex with more affinity. Therefore, Klotho determines the kidney-specific action of FGF23. Increase in FGF23 or Klotho levels due to genetic defects or ectopic production results in low serum phosphorous levels in humans. Contrary to this, low FGF23 or Klotho levels lead to hypophosphatemia and ectopic calcification. Mouse genetics studies revealed that osteoblast product, osteocalcin, in its undercarboxylated stage acts on the pancreatic beta-cells to enhance insulin production and on peripheral tissues to increase glucose utilization as a result of increased insulin sensitivity and to reduce visceral fat. In addition to this, undercarboxylated osteocalcin may also have another hormonal role, this time as a mediator of testosterone secretion. Osteocalcin was shown to induce testosterone production in Leydig cells of the testes both in ex vivo and in vivo studies. In both localizations, at the pancreas and at the testes osteocalcin acts through the GPCR6A receptor, this activates the cAMP response element-binding protein signaling pathway. Thus, this review reports the recent studies indicating bone ’s role as an endocrine organ.

Clinical symptoms of vitamin D deficiency may be quite misleading and masked as rare hereditary syndromes. We describe a family, sister and brother presented with the pain in lower extremities at the age of 14 and 16years accordingly, with severe vitamin D deficiency that was misdiagnosed in the course of the disease with pseudohypoparathyroidism and 1-alpha-hydroxylase deficiency. They benefited from treatment with alfacalcidol and ossein-hydroxyapatite complex supplement which were further discontinued due to socioeconomic factors. At presentation after 2 years without treatment extremely low 25(OH)D levels were revealed. The patients' family history was remarkable for the same clinical features in mother and her Indian ancestry. Thus we describe an uncommon manifestation of severe vitamin D deficiency in a familial setting which emphasizes the necessity of vitamin D testing in calcium or parathyroid disorders.

В статье представлен обзор современной литературы и результаты наших исследований, обобщающие экспериментальные и клинические данные о влиянии цинакалцета на гормонально-биохимические показатели фосфорно-кальциевого обмена, на маркеры костного метаболизма, минеральную плотность костей, также на гистоморфометрические показатели почечной остеодистрофии у гемодиализных пациентов с вторичным гиперпаратиреозом

Постепенное увеличение продолжительности жизни человека, стремление к улучшению ее качества требует улучшения результатов профилактики и лечения остеопороза. Основную часть лиц, подверженных ОП, составляют женщины в менопаузе. Разносторонний подход к проблеме восстановления баланса костного метаболизма привел к внедрению в практику препаратов с различными механизмами действия. В последнее время крайне важным аспектом является повышение приверженности к лечению пациентов, получающих многолетнее лечение остеопороза. Инновационным шагом является внедрение в практику применения нового препарата моноклонального человеческого антитела к лиганду RANK деносумаб. В обзоре представлены результаты сравнительных многоцентровых слепых рандомизированных исследований эффективности деносумаба и пероральных бисфосфонатов. Показано более выраженное достоверно влияние деносумаба (подкожно 60 мг 1 раз в 6 мес.) на прирост МПК во всех отделах скелета (как богатых трабекулярной, так и кортикальной костной тканью), значимое снижение риска переломов при хорошей переносимости лечения.

In this critical review, we have summarized the specific evidence on ibandronic acid (Bonviva) efficacy, tolerability, feasibility and safety acquired from randomized controlled clinical trials, meta-analyses, bridging trials, long-term extension studies, observational studies and clinical experience. We have paid special attention to reviewing the surrogate endpoints, which are routinely used in clinical practice to estimate the treatment efficacy as well as those high technology methods that are currently used in research centers to predict anti-fracture efficacy. Although the only registered indication for Bonviva in Russia is for postmenopausal osteoporosis, we have reviewed the available clinical trials on the efficacy of ibandronic acid to prevent postmenopausal osteoporosis, to treat low bone mass in males, to treat and prevent glucocorticoid induced osteoporosis and other types of secondary osteoporosis and, in particular, in patients after organ transplantation. In addition to this, we have extensively discussed the currently available data on the safety of pharmacologic treatment for osteoporosis.

The authors review the current literature data on the pathogenesis, clinical manifestations and treatment of glucocorticoid induced osteoporosis in patients with endogenous hypercortisolism. High levels of glucocorticoids lead to bone loss, bone quality deterioration and low traumatic fractures as a consequence of reduced bone formation. In addition to this, muscle weakness and sex steroids hormone abnormalities increase the risk of falls and fractures. The new available data on possible mechanisms of these changes including the involvement of RANKL/RANK/OPG, Wnt-betacatenin signaling pathway and pathogenesis of myopathy are discussed. This review also outlines the practical recommendation and new questions that should be evaluated in future research.

Обзор литературы посвящён патогенетической обоснованности, эффективности и безопасности применения деносумаба в терапии постменопаузального остеопороза. Обсуждается механизм действия препарата, сходства и отличия по отношению к другим препаратам для лечения остеопороза. Подробно представлены результаты II и III фаз клинических исследований деносумаба, в том числе в сравнении с алендроновой кислотой и возможности назначения деносумаба после лечения бисфосфонатами. Отдельное внимание уделяется безопасности и практическим аспектам терапии деносумабом

Primary hyperparathyroidism (PHPT) is a common endocrine disorder that affects bones, urinary tract, cardiovascular system, gastrointestinal tract, and another organs and tissues. The most cases of PHPT are mild forms and those patients have nonspecific symptoms, which require careful diagnostic considerations and choice of treatment. There is not enough data about prevalence of PHPT, especially it's mild forms, in Russian Federation, and future epidemiological research needs to be done. Present literature review includes information about etiology, pathogenesis, clinical findings, diagnostic and differential diagnostic, indication for surgery and medical treatment of PHPT. The review is based on data of studies from the different countries and few studies from Endocrine science center.

Central diabetes insipidus is a rare pituitary disease due to impairment of synthesis or/and secretion of vasopressin (AVP), characterized by polyuria, polydipsia, low urine osmolality and hyperosmolality of plasma. Main therapy for CDI is substitutive therapy with desmopressin. Lately, it has been shown that AVP stimulates bone formation through the induction of PG synthesis in mesangial cells, contributing to prevent osteoporosis. Pivonello et al. (1998) found that patients with CDI even on nasal desmopessin therapy had a significant impairment in BMD and serum osteocalcin. The aim of this study was to assess the biochemical parameters of bone metabolism and the bone mineral density (BMD) in patients with idiopathic variant of CDI, treated with oral desmopressin. In 24 patients with idiopathic CDI, treated with oral desmopressin and 24 healthy controls we evaluated BMD (analyzer Prodigy, Lunar, DXA), serum osteocalcin (OK) and C-terminal telopeptide of type I collagen (CTx), (ECLIA, Roche Elecsys 1010/2010) as well as calcium total, ionized calcium and alkaline phosphatase (analyzer Hitachi 912, commercial kits Roche). Anterior pituitary dysfunction and concomitant conditions associated with osteoporosis were eliminated on clinical and laboratory basis. The results showed no significant differences between study groups with the exception for ionized calcium which was higher in the group of CDI (p=0,02). We were not able to confirm detrimental effects of idiopathic CDI on BMD and biochemical markers of bone metabolism.

Приведены 2 клинических случая поздней диагностики тяжелых форм первичного гиперпаратиреоза. повлекшие за собой неоправданные врачебные манипуляции, и развитие тяжелых осложнений заболевания. В первом случае из-за ошибочного диагноза остео... и нерасп ПГПТ пациентки подверглись многократным операциям на нижней челюсти. Во втором случае поздний диагноз ПГПТ у молодого пациента, несмотря на успешное хирургическое вмешательство привел к прогрессирующей ХПН и развитию вторичного гиперпаратиреоза.

For many years, hyperparathyroidism, including primary, primarily associated with severe pathology of the osseous system and kidneys, was considered a rare disease. The widespread introduction into the clinical practice of the determination in the blood of calcium, and then parathyroid hormone, and osteodensitometry made it possible to recognize this disease more often and at earlier stages and to treat it more successfully. By now, the specific gravity of mild and asymptomatic forms of hyperparathyroidism has increased from 10-15% in the 1980s to 80%. Conservative management of these forms of hyperparathyroidism requires more thorough research on the prognosis of survival, duration and quality of life, and the risk of developing associated diseases in these patients.