[Preliminary results of an open-label observational study evaluating the efficacy and safety of Prolia used in women with postmenopausal osteoporosis].

AIM: To evaluate the efficacy and safety of Denosumab (Prolia), a first-line osteoporosis (OP) medication that is a fully human monoclonal antibody to the receptor activator of nuclear factor xB ligand (RANKL), within an open-label observational study. SUBJECTS AND METHODS: Patients aged 50 years or older with postmenopausal OP, who were treated with Prolia in clinical practice, were examined. The concentrations of the bone resorption (BR) marker of C-terminal telopeptide and other laboratory indicators (total serum calcium, total alkaline phosphatase, and creatinine) were measured following 3 months. Adverse drug reactions were recorded. RESULTS: Three months after initiation of the investigation, there was a significant decrease in the BR marker C-terminal telopeptide (by 89%; p<0.0001). There were rare adverse reactions: hypocalcemia in 3 (5.9%) patients, arthralgias in 2 (3.9%), and eczema in 1 (1.9%). There were neither serious adverse events nor study withdrawal cases. CONCLUSION: The preliminary results of the open-label study of Prolia in postmenopausal OP suggest that the significantly lower BR activity determines the efficacy of this drug and its high safety.

[Multiple endocrine neoplasia type 1 variants and phenocopies].

Multiple endocrine neoplasia type 1 (MEN1) is a rare autosomal dominant hereditary disease due to a mutation in the MENI tumor suppressor gene. The risk of the disease in first-degree relatives of MEN1 mutation carriers is 50%. MENI gene mutations are not identified in 10-30% of familiar MEN1 patients and in 60-80% of sporadic MEN1 cases, which can be explained by mutations in the noncoding regions of the MEN1 gene, large gene deletions or mutations in other yet unknown genes. Molecular genetic testing can exclude the diagnosis of MEN1 in patients who do not harbor the MEN1 mutation, thus revealing a MEN1 phenocopy. This obviates the need for annual screening for the early detection of other remaining components of the disease and its risk in progeny.

[The saliva cortisol level test using the automatic immunochemical analyzer Cobas e601 (Roche) to diagnose endogenous hypercorticalism in patients with obesity].

The saliva cortisol level test applies to diagnose endogenous hypercorticalism. However the methods of die format immunoassay traditionally used do not make it possible to get the study results on-the-fly. Also, reference interval and optimal takeoffs differ under implementing various techniques of cortisol tests. The purpose of actual study is to investigate the possibilities of electrochemiluminescent technique of testing free cortisol in saliva. The device Cobas e601 was applied to diagnose endogenous hypercorticalism in patients with obesity. The saliva samples were collected at 11 PM from 98 healthy volunteers and 123 patients with obesity (in 45 cases endogenous hypercorticalism was diagnosed). In total, 205 persons donated saliva at 11 PM two days running to evaluate the technique reproducibility. The samples of 197 individuals were frozen to implement the immune-enzyme assay. The minor test with dexamethasone was applied to patients with suspected endogenous hypercorticalism. The diagnosis of endogenous hypercorticalism was finally confirmed after the results of histological analysis of post-operative material or autopsy. Among healthy volunteers, the reference interval on indicators consisted 0.5-9.4 nMol/l. The correlation coefficient under free cortisol measuring at the same time two days running was -0.785. The optimal takeoff to diagnose endogenous hypercorticalism in patients with obesity consisted 9.4 nMol/l, sensitivity--84.4% (95% confidence band 71.2-92.2%), specificity--92.3% (95% confidence band 84.2-96.4%), predictive value of positive result--11.0 (95% confidence band 5.0-23.9), predictive value of negative result--0.17 (95% confidence band 0.08-0.33) and likelihood ratio for positive result--65.1 (95% confidence band 20.4-207.6). The two-fold cortisol test in saliva using immune-enzyme assay and minor test with dexamethasone with their diagnostic capabilities corresponded to one-fold saliva free cortisol test using electrochemiluminescent technique. The one-fold free cortisol test in saliva collected in 11 PM using the analyzer Cobas e601 for electrochemiluminescent immunoanalysis is a convenient and informative endogenous hypercorticalism screening technique in patients with obesity.

[Sexual and reproductive function in males with somatotropinoma].

The examination of 72 males with somatotropinoma has found that 65% of such patients have hypogonadism which is essential in pathogenesis of sexual dysfunction and spermatogenetic disorders. However, hypogonadism in males with somatotropinoma does not provoke sexual dysfunction in most the cases. High production of somatotropic hormone and insulin-like growth factor 1 in somatotropinoma leads to prostatic hyperplasia which is not accompanied with a rise of a PSA level and symptoms of infravesical obstruction.

[Prognostic value of of the expression Ki-67, CD31, and VEGF in somatotropinomas].

Pituitary adenomas are benign, but 30-50% of patients do not achieve remission after treatment. The purpose of the study was to analyze the prognostic value of immunoexpression of the proliferation marker Ki-67 and the angiogenetic factors CD31 and VEGF in somatotropinomas. Ki-67, CD31, and VEGF were immunohistochemically studied in the samples of 52 somatotropin-removed samples; medical records were used to analyze the outcome of treatment in the early and late postoperative periods. Ki-67 immunoexpression proved to be significantly higher in the patients who had not achieve remission both in the early (p = 0.042) and late (p = 0.012) postoperative period than in those who had achieved remission and in patients who were resistant to postoperative treatment with somatostatin analogues (p = 0.040) than in those who were sensitive to therapy. The immunoexpression of CD31 and VEGF was not associated with the outcome of treatment. Thus, high Ki-67 levels may be regarded as a poor postoperative prognostic factor in acromegaly.

[Maldiagnosis of giant-cell tumor of the bone in a patient with hyperparathyroid osteodystrophy].

The paper describes a case of maldiagnosis of giant-cell tumor in a patient with parathyroid osteodystrophy, in this connection elbow joint resection and replacement were made. Parathyroid adenoma with the symptoms of primary hyperparathyroidism was diagnosed only two years after surgery. Progression of diseases was accompanied by severe bone changes and the development of urolithiasis complicated by chronic renal failure. Thus, the interpretation of bone tissue changes without considering clinical and laboratory data led to the unwarranted surgical intervention and the late diagnosis of primary hyperparathyroidism. Differential diagnosis of a giant-cell tumor should be made, by obligatorily considering clinical and laboratory data, including the parameters of calcium metabolism.

[Vitrum osteomag in prevention of osteoporosis in postmenopausal women: results of the comparative open multicenter trial]. / Vitrum osteomag v profilaktike osteoporoza u zhenshchin v postmenopauze: rezul'taty sravnitel'nogo otkrytogo mnogotsentrovogo issledovaniia.

AIM: To investigate efficacy, tolerance and safety of the drug vitrum osteomag one tablet of which contains 600 mg calcium (1500 mg calcium carbonate), 200 IU of cholecalcepherol, 40 mg of magnesium, zinc (7.5 mg), copper (1 mg), manganese (1.8 mg) and boron (250 mcg) in women with osteopenia for prevention of osteoporosis. MATERIAL AND METHODS: A multicenter comparative open trial of vitrum osteomag influence on mineral bone density (MBD), change of pain syndrome in bones, index of calcium-phosphorous metabolism covered 334 postmenopausal women with osteopenia. MBD was measured in low-back spine and proximal part of the hip with DEXA method. All the patients were divided into 3 groups: 125 women taking 2 tablets of vitrum osteomag daily for 12 months (group 1); 111 women taking 1500 mg calcium carbonate (group 2); 96 women--control group (only observation). RESULTS: Vitrum osteomag relieved pain in the back and joints, had a positive effect on bone density (+1.5%) and proximal parts of the hip (0.6-0.93%) exceeding the effect of calcium carbonate only which preserves the initial MBD in low back spine but does not prevent bone loss in the hip. MBD dynamics in patients given vitrum osteomag differs essentially from one in the control group (from -1.9 to -2.91%) which demonstrates a reliable preventive anti-osteoporotic effect of this medication. The drug increases the level of general and ionized calcium in blood but does not cause hypercalcemia lowering the level of parathormone in blood. The rate of side effects in group 1 was 14.4% and did not differ much from that in group 2 (16.2%). CONCLUSION: The results of the study allow to recommend vitrum osteomag for prophylaxis of a rapid loss of bone tissue mineral density.

[Osteoporosis: diagnosis of disorders of bone tissue and calcium-phosphorus metabolism (lecture)]. / Osteoporoz: diagnostika narushenii metabolizma kostnoi tkani i kal'tsii-fosfornogo obmena (lektsiia).

Tentative diagnoses of lymphadenitis or Hodgkin's disease were not confirmed in a 12-year-old child by cytological investigations. Along with lymphoid cells, individual leukocytes, histiocytes, macrophages, and glandular cancer cells, the cytological preparation of the cervical lymph node biopsy specimen contained uncommon multinuclear cells looking like interfollicular thyroid islets. This indicated cancer metastasis and the site of primary involvement: the thyroid. The diagnosis was confirmed by the histological and radionuclide methods.

[Bone tissue in patients with hyperprolactinemic hypogonadism]. / Sostoianie kostnoi tkani u bol'nykh s giperprolaktinemicheskim gipogonadizmom.

Sixteen women with hyperprolactinemia were examined for Ca metabolism, osseous metabolism, mineral saturation of bone tissue in the thoracic portion of the spine and radius. Lowered mineral saturation of the thoracic vertebrae was detected in 69% of the examinees, that of the distal segment of the radius in 44%. Reduction of the mineral saturation of the spine was in negative correlation with the blood prolactin level and length of amenorrhea. No changes in the bone resorption biochemistry or Ca metabolism were detected. A marked reduction of blood osteocalcin level that reflects osteoblast function was detected, its blood concentration being in negative correlation with prolactin level. No relationships between mineral saturation of bone tissue, prolactin, and osteocalcin, on the one hand, and blood estradiol level, on the other, were observed. These data suggest that osteopathy in hyperprolactinemic hypogonadism is due to reduced bone formation and not to reduced estradiol production.

[Comparative evaluation of the effectiveness of vitamin D3 preparations (1-alpha-hydroxy- and 1-alpha,25-dihydroxycholecalciferol in various forms of osteoporosis and osteomalacia]. / Sravnitel'naia otsenka éffektivnosti preparatov vitamina D3 (1-alpha- i 1-alpha,25-dihydroxycholecalciferol) pri razlichnykh vidakh osteoporoza i osteomaliatsii.

Clinical investigations have shown that 1 alpha-hydroxycholecalciferol (oxydevit, alphacalcidiol) and 1 alpha, 25-dihydroxycholecalciferol (rocaltrol) are act vitamin D3 agents producing a positive clinical effect in different types of osteoporosis and osteomalacia. Clinical improvement of the patients' status (alleviation of the pain syndrome, an increase in motor activity) was noted in 1-2 mos., an x-ray picture of regeneration of the bone structure of both axial and peripheral skeleton--in 6-12 mos. after the initiation of therapy. Therapy was attended by an increase in the serum content of total and ionized calcium, the return of alkaline phosphatase activity to normal, and a decrease in the level of parathormone. During prolonged therapy these agents administered at daily doses of 0.25-2 micrograms caused no pathological side-effects and hypercalcemia. In osteoporotic conditions all these drugs were equal in their clinical effectiveness. Rocaltrol has some advantages in the presence of associated liver pathology.