BACKGROUND: Patients with endogenous hypercortisolism have reduced bone mineral density (BMD) and trabecular bone score (TBS) that are the causes of secondary osteoporosis and low-traumatic fractures. It is well known that radical treatment (neurosurgery or radiosurgery) of Cushing’s disease leads to a decline of cortisol levels in all body fluids to normal values. However, it is still uncertain whether bone tissue structure, and particularly its microarchitecture, does recover in remission of the disease.

AIMS: To evaluate an influence of hormone activity (presence or absence of remission) in patients with Cushing's disease on changes of bone structure measurements in accordance with DXA values (TBS, BMD, T- and Z-scores), as well as significance of such changes in 12 and 24 months after neurosurgical treatment.

MATERIALS AND METHODS: In patients with confirmed active Cushing's disease (ACTH-producing pituitary adenoma) (n = 44) and in control group of healthy volunteers (n = 40), BMD in lumbar spine (L1-L4) and simultaneously TBS, in cut-off points before neurosurgical treatment (in both groups) and in 12 and 24 months after it (only in patients), were assessed. We diagnosed presence or absence of disease remission at cut-offs. All measurements were performed using a GE iDXA device (GE Healthcare Lunar, Madison, Wisconsin, USA). The TBS was calculated simultaneously from taken BMD scans, blinded to clinical outcome using TBS iNsight software v2.1 (Medimaps, Merignac, France). The activity of Cushing’s disease was evaluated using late-night salivary cortisol (LNSC, at 23:00). To determine the differences in DXA and TBS values before and after neurosurgical intervention depending on remission occurrence, covariate analysis (ANCOVA) was applied.

RESULTS: There were found significant changes in TBS, BMD and T-score values in 12 months after neurosurgical treatment associated with presence or absence of disease remission (p = 0.039, 0.046 and 0.048, respectively). No differences in Z-score as well as in all measurements in 24 months, that might be associated with remission occurrence, were revealed. The gain in all DXA measurements (including TBS) during 24 months of observation period was statistically significant when analyzing data using Student’s paired t-test. However, the values corresponding to the age references had not been achieved for the specified time interval.

CONCLUSIONS: Patients with Cushing’s disease have lower TBS values. In remission conditions TBS is getting significantly higher. The increase in BMD and TBS occurs during 24 months after achieving remission of Cushing’s disease but doesn’t lead to a full restoration of normal bone mass and microstructure throughout observation period of 24 months.

In this review, we discuss the main reasons for the vitamin D insufficiency in Russian Federation, as well as data on the prevalence of vitamin D deficiency among various population groups and regions, which confirm the widespread prevalence of vitamin D deficiency in the country. The discussed data suggest that the current vitamin D insufficiency in Russian population (reduced levels of 25(OH)D occurs in 50 - 94% of general population) is due to both a low level of its endogenous synthesis and insufficient intake from food : the territory of the country is located in a zone of low insolation, and at the same time, the main natural sources of vitamin D (sea fish of fatty varieties) and fortified with vitamin D products are very limited in the diet of the population. Taking measures to improve the status of vitamin D and maintaining the optimal serum levels of 25(OH)D in children and adults, adequate vitamin D intake will improve the condition of the musculoskeletal system, as well as reduce the risk of development and improve the control of some chronic diseases.

Osteoporosis medications are divided into two groups: those inhibiting bone resorption and formation (bisphosphonates and denosumab), and those stimulating bone formation i.e. having an anabolic effect. The latter include teriparatide, parathyroid hormone 1-84 and abaloparatide, all of which stimulate bone resorption as well as bone formation, which limits their anabolic effect.

The discovery of sclerostin – the key inhibitor of bone formation – has led to development of the concept that inhibition of this protein could stimulate bone formation. Romosozumab is a human monoclonal antibody to sclerostin that binds to sclerostin and enables Wnt-signaling pathway ligands and their co-receptors to interact with each other, which, in turn, leads to increased bone formation and bone mineral density. Unlike classical anabolic drugs in osteoporosis treatment, romosozumab stimulates bone formation and inhibits bone resorption. In clinical trials, romosozumab showed marked increase in lumbar spine and hip bone mineral density. Presented article contains information about pre-clinical and clinical studies of romosozumab.

MELAS syndrome belongs to the group of progressive mitochondrial diseases associated with point mutations in mitochondrial DNA, and includes mitochondrial encephalomyopathy, lactic acidosis, stroke-like episodes, which can combined with endocrine disorders (thyroid, parathyroid and pancreas). The frequency of hypoparathyroidism in the framework of the syndrome is less than 0.5%.

Verification of the MELAS syndrome is associated with certain difficulties due to low incidence of the disease and variety of clinical manifestations and requires continuity in the work of doctors of various specialties: neurologists, endocrinologists and audiologists. Confirmation of the diagnosis is carried out by molecular genetic test of mitochondrial DNA in lymphocytes, in some cases muscle tissue biopsy analysis.

In the article, we present a rare diagnosis case young patient with MELAS syndrome based on the presence of unclear hypoparathyroidism in combination with neurological symptoms, diabetes mellitus, lactic acidosis and hearing loss. MELAS syndrome was confirmed by a genetic blood test. In the debut of hypoparathyroidism, diabetes mellitus, hypothyroidism of the MELAS syndrome were easily compensated on replacement therapy.