[Clinical features, diagnostics and treatment of FGF23 secreting tumors: series of 40 clinical cases].

INTRODUCTION: Tumor-induced osteomalacia is an acquired rare disease manifested by hypophosphatemic osteomalacia due to excessive secretion of fibroblast growth factor 23 (FGF23). FGF 23 is a non-classical hormone secreted by bone tissue (osteocytes) and regulates phosphorus metabolism.The aim of this work is to present clinical experience in the diagnosis, treatment and rehabilitation of patients with tumor-induced osteomalacia. MATERIALS AND METHODS: 40 patients with clinically-confirmed tumor-induced osteomalacia were included in the study, 34 of whom had the tumor localized, 27 underwent surgical treatment and 21 achieved stable remission. RESULTS: The median age was 48 [41; 63] years, 43% were men, the time left from the the onset of the disease was 8 [4; 10] years. Biochemical findings were hypophosphatemia 0.47 [0.4; 0.53] mmol/l, a decrease in the tubular reabsorption phosphate 62 [52; 67]%, and an increase in alkaline phosphatase of 183 [112; 294] units/l. At the time of diagnosis, 100% had multiple pathological fractures, only 10% could move independently, and 77.5% classified the pain as unbearable (8-10 points according to the 10-point pain syndrome scale ). Among the methods used to detect tumors, the most sensitive were scintigraphy with tectrotide with SPECT/CT 71.4% (20/28) and MRI 90% (18/20). In 35% of cases, the tumor was localized in soft tissues and in 65% in bone tissue; The tumor was most often detected in the lower extremities, followed by the head in frequency of localization. 18 patients currently have no remission and they receive conservative treatment (phosphorus and alfacalcidol n=15 and burosumab n=3). In case of achieving remission (n=21), regression of clinical symptoms and restoration of bone and muscle mass was observed. Extensive excision of the tumor without prior biopsy resulted in the best percentage of remission - 87%. CONCLUSION: Tumor-induced osteomalacia is characterized by severe damage to bone and muscle tissue with the development of multiple fractures, muscle weakness and severe pain syndrome. In laboratory diagnostics, attention should be paid to hypophosphatemia, a decrease in the tubular reabsorption phosphate index and increased alkaline phosphatase. The use of functional diagnostic methods with a labeled somatostatin analogue to the subtype 2 receptor and MRI with contrast enhancement are the most accurate methods of topical diagnostics. In case of localization of the tumor, a wide excision without a preliminary biopsy is recommended.

Influence of bisphosphonates on calcium metabolism and bone tissue during simulation of the physiological effects of microgravity.

At present a significant experience has been gathered in experimental and clinical use of synthetic derivatives of bisphosphonic acid. Purpose of our study was to investigate the effects of bisphosphonates on calcium metabolism and bone tissue in humans and animals under the conditions simulating the physiological effects of microgravity. In a series of experiments with animals the effectiveness of various preparations and treatment plans was compared Action of 1-hydroxyethyliden-1, 1-bisphosphonic acid (EHBP, xydiphon) on calcium metabolism and bone tissue in human was the subject of experiments with long-term head-down tilt (HDT).

On the contribution of space medicine in the public health care.

With the beginning of space era, a new branch of medicine has arisen and has been developing along with human exploration of outer space. And even though space medicine mainly faces the same problems as traditional medicine--cosmonauts health care and their high efficiency--this branch, has its own features, associated with the unusual factors of space flight, of which weightlessness is the major one. During the development of manned cosmonautics (duration of a human stay in space has reached already 438 days), methods of cosmonauts medical support and monitoring of their condition have been developed, knowledge of human possibilities and methods of process of organism adaptation to various and frequently severe conditions of external environment have increased. All this led to the fact that nowadays space medicine can become useful for improvement of human health care not only in space but also on the Earth. Moreover, the problem of implementation of cosmonautics achievements, and in particular of space medicine, in practice of public health care presents one of the most important issues concerning human health care. It is also connected with public opinion which is more and more concerned about the efficiency of significant expenses on space activities, especially lately. People often are set by the questions: what has space given, what fruits has space research provided to mankind, which results of this research can be used on the Earth already today for improvement of their life, for discussion of many difficult earthly problems? In terms of using cosmonautics possibilities, its achievements for health care and treatment, it is possible to define a few branches, in which purposeful studies are carried out.

Education programme on aerospace and environmental medicine for medical faculty of Lomonosov Moscow State University.

The problems and approaches to organisation of the education process in the field of aerospace and environmental medicine for medical students are discussed. Original education developed on the basis of Russian experience in space biology and physiology, environmental medicine, aerospace medicine and medical support during spaceflight. The main goals of these programs are to acquaint students with: interaction of living organisms with natural and artificial surroundings, including space flight conditions; the physiological reactions on extreme environmental factors; basic mechanisms of human adaptation to space flight and particularly to microgravity; the current research in space medicine and new telecommunication technologies. All programs are formed in accordance with contemporary progress in life sciences and revealed a result of the interdisciplinary approach to education process.

Bone and body mass changes during space flight.

Body mass, calcium and skeletal changes occur in humans who have worked in microgravity. Physiologic changes are seen as early as one week and are still occurring 312 days into space flight. The physiologic changes in bone and mineral metabolism may be among those which limits long duration space flight if an adequate countermeasure is not developed. The purpose of this paper is to summarize what is known about calcium dynamics and bone mineral changes as well as associated changes of body mass induced by space flight. The data reported is from a variety of studies conducted in both actual and simulated space flight.

Effect of exercise and bisphosphonate on mineral balance and bone density during 360 day antiorthostatic hypokinesia.

As we enter a phase of space exploration that will involve long-duration flights, there is a need to use ground-based models to study the long-term effects of countermeasures to prevent the loss of bone mineral in microgravity. Mineral balances, hormone levels, and bone density were measured for 360 days in nine bed rest subjects treated with an exercise program used by cosmonauts. Four of these subjects received the bisphosphonate, ethane-1-hydroxy-1-disphosphonate, 900 mg daily, a drug known to inhibit bone resorption. Compared to a 120 day control period, the bisphosphonate combined with exercise reduced negative calcium balances by 50% for the first 120 days, 80% for the second 120 days, and 69% during the third 120 days. Exercise alone had no effect until the second 120 day period, when calcium balance improved 52%. Negative phosphorus balances were not affected by either treatment. Magnesium balances were negative during the first 120 days and returned to nearly normal during the last 240 days in both groups. The combined exercise and bisphosphonate treatment prevented increases in serum ionized calcium and decreases in plasma calcitonin during the first 120 days, as well as trends toward decreases in the mineral density of the femoral neck. These results suggest that bisphosphonates can be efficiently used together with exercise to reduce calcium loss and prevent some of the changes in mineral metabolism during long-term simulated microgravity.