Vitamin D status in residents of Tyumen region

BACKGROUND: The high prevalence of vitamin D deficiency worldwide is often associated with the region of residence. AIMS: to study the level of vitamin D in serum of residents living in Tyumen region, to assess the frequency of occurrence of insufficiency and deficiency of vitamin D in the region. MATERIALS AND METHODS: Observational, single-site, transverse, selective, uncontrolled study of the prevalence of vitamin D deficiency among adults in Tyumen region, conducted from November 2017 to March 2018. RESULTS: Optimal levels of 25(OH)D in the residents of the Tyumen region were found in 7.3% of patients, its insufficiency was registered in 22.0% of cases, and defficiency – in 70.7%. There was a weak correlation relationship between lower values of 25(OH)D in those examined with obesity according to body mass index (r = -0.104, p <0.05) and waist circumference (r = -0.239, p <0.05), and with greater body mass (r = -0.130, p <0.05). CONCLUSIONS: There is a high prevalence of insufficiency and deficiency of vitamin D among the adult population living in Tyumen region has been revealed. Additionally, it has been established that the level of vitamin D is not associated with gender and age, but is associated with BMI, waist circumference and body weight of patients

The «cut-off point» of vitamin D: a method of suppressing excessive secretion of PTH

BACKGROUND: The subject of discussion is the issue of the separation point, which determines sufficient levels of vitamin D for bone health. When determining the adequate reference range of vitamin D, researchers are mainly guided by the results of research, where the level of 25(OH)D is determined, at which the PTH level decreases and reaches a plateau. AIM: To establish the «cut-off point» of vitamin D by suppressing excessive secretion of PTH. MATERIALS AND METHODS: Observational, single-site, single-stage, selective, uncontrolled study of the search for vitamin D levels by the effect on PTH secretion in residents of Tyumen region was conducted (n = 176). All selected study participants determined the level of 25(OH)D and PTH in serum. The calculation of the «cut-off point» was carried out using the method of searching for changes in the correlation dependence of PTH on the level of vitamin D, followed by verification of the data obtained using ROC analysis. RESULTS: A mathematical analysis of the dependence of 25(OH)D and PTH showed the “cut-off point” of vitamin D, equal to – 23.6 ng/ml. CONCLUSION: The “cut-off point” of 23.6 ng/ml is optimal for suppressing excessive PTH secretion. The data obtained may be an incentive for further working out the “cut-off point” of vitamin D for the Russian population and can be used to clarify the classification of deficiency, insufficiency and optimal levels of vitamin D for the population of the Russian Federation

The prevalence of vitamin D deficiency in Russian Federation

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

Sclerostin antibodies as novel anabolic therapy for osteoporosis

Osteoporosis medications are dividedinto 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

The relationship of vitamin D status with the development and course of diabetes mellitus type 1

Type 1 diabetes mellitus (T1DM) is a chronic autoimmune disease that develops as a result of a genetic predisposition and environmental factors. Literature data indicate that the suboptimal status of vitamin D can be considered as a risk factor for the development of T1DM, especially at some stages of life. Adequate vitamin D supplementation in childhood may provide a protective effect and reduce the risk of developing T1DM at a later age. Pathogenesis of T1DM predisposes to abnormalities in the metabolism of vitamin D, including the development of vitamin D deficiency. Moreover, the immunomodulating effect of calcitriol (induction of immune tolerance and T-cell anergy, impaired B-cell activity and antibodies production) suggests the therapeutic potential of vitamin D in autoimmune diseases, including T1DM. A number of studies have demonstrated the positive clinical effects of various vitamin D preparations with respect to maintaining residual β-cell function, improving glycemia control in patients with T1DM. Determining the optimal doses of vitamin D for patients with T1DM may contribute to disease control and prevention of complications

Rare genetic diseases of the bone tissue: the case of a family with osteogenesis imperfecta and X-linked hypophosphataemia

Osteogenesis imperfecta (OI) and X-linked hypophosphataemia (XLH) are rare genetic diseases, which lead to childhood-onset bone fragility, low-trauma fractures and limb deformities. OI occurs as a result of impaired type 1 collagen synthesis at different stages, depending on the type of a genetic mutation, which leads to bone strength impairment. In most cases OI is a disorder with an autosomal dominant inheritance. However, there are also cases of autosomal recessive inheritance. To date, 16 types of OI are distinguished, with type 2 being the most severe due to 100% mortality rate in neonatal and perinatal periods. XLH is characterized by altered bone mineralization due to impaired phosphorus absorption and reabsorption, as a result of mutations in the PHEX gene. The bone tissue softens, and this process is accompanied by deformities in long tubular bones. In this article we describe the family, in which both diseases are presented, despite their rarity. The case is investigated from points of view: the clinicians and the patients perspective

Lanreotide Autogel 120 mg at extended dosing intervals in patients with acromegaly biochemically controlled with octreotide LAR: The LEAD study

Objective: To evaluate extended dosing intervals (EDIs) with lanreotide Autogel 120 mg in patients with acromegaly previously biochemically controlled with octreotide LAR 10 or 20 mg. Design and methods: Patients with acromegaly had received octreotide LAR 10 or 20 mg/4 weeks for R6 months and had normal IGF1 levels. Lanreotide Autogel 120 mg was administered every 6 weeks for 24 weeks (phase 1); depending on week-24 IGF1 levels, treatment was then administered every 4, 6 or 8 weeks for a further 24 weeks (phase 2). Hormone levels, patient-reported outcomes and adverse events were assessed. Primary endpoint: proportion of patients on 6- or 8-week EDIs with normal IGF1 levels at week 48 (study end). Results: 107/124 patients completed the study (15 withdrew from phase 1 and two from phase 2). Of 124 patients enrolled, 77.4% were allocated to 6- or 8-week EDIs in phase 2 and 75.8% (95% CI: 68.3-83.3) had normal IGF1 levels at week 48 with the EDI (primary analysis). A total of 88.7% (83.1-94.3) had normal IGF1 levels after 24 weeks with 6-weekly dosing. GH levels were ≤2.5 mg/l in >90% of patients after 24 and 48 weeks. Patient preferences for lanreotide Autogel 120 mg every 4, 6 or 8 weeks over octreotide LAR every 4 weeks were high. Conclusions: Patients with acromegaly achieving biochemical control with octreotide LAR 10 or 20 mg/4 weeks are possible candidates for lanreotide Autogel 120 mg EDIs. EDIs are effective and well received among such patients

Diagnostic value of salivary cortisol in 1-mg dexamethasone suppression test

BACKGROUND: Late-night salivary cortisol and serum cortisol measurements after 1-mg Dexamethasone Suppression Test (1-mg DST) are routinely used to diagnose Cushing’s syndrome (CS). Measuring morning salivary instead of serum cortisol after 1-mg DST would make the diagnostics of CS fully non-invasive. AIM: To evaluate the diagnostic accuracy of salivary cortisol in 1-mg DST as measured by electrochemiluminescence assay (ECLIA). MATERIALS AND METHODS: We combined a cohort diagnostic study, including 164 participants (132 females, 32 males) aged from 18 to 77 years: 110 were overweight or obese as increased BMI is the most common sign of Cushing’s Syndrome (CS), and 54 healthy volunteers. In each cohort late-night salivary cortisol was measured (at 23:00) followed by 1-mg DST and blood and salivary sampling for cortisol measurement the next morning at 08:00-09:00. Cortisol in saliva and serum were measured on automatic analyzer Cobas е 601 by F. Hoffmann-La Roche Ltd, using ECLIA. The final diagnosis was confirmed by the histological evaluation after surgery or using a follow-up observation in patients with obesity to exclude Cushing’s syndrome manifestation. RESULTS: Among 110 patients, 54 subjects were finally confirmed as having Cushing's syndrome. Reference interval for salivary cortisol after 1-mg DST was estimated to be 0,5–12,7 nmol/l (5–95 procentile). Maximal salivary cortisol level in 1-mg DST registered in healthy person was 29,6 mmol/l. Areas under the curve (AUC) were as following: for salivary cortisol in 1-mg DST – 0,838 (95% СI 0,772–0,905), for blood cortisol in 1-mg DST – 0,965 (95% CI 0,939–0,992) and for late-night salivary cortisol – 0,925 (95% CI 0,882–0,969). The optimal cut-off point for salivary cortisol after 1-mg DST was estimated as 12.1 nmol/l (sensitivity 60%, specificity 92,9%) among CS versus healthy subjects; 12,6 (sensitivity 58,2%, specificity 96,2%) among patients with obesity and CS; and – 12,2 nmol/l (sensitivity 60,7%, specificity 93,4%) among CS and both obese and healthy control subjects. Considering small difference between cut-off points, the recommended cut-off value for salivary cortisol after 1-mg DST is recommended to be 12,0 nmol/l if measured by ECLIA. CONCLUSION: Although salivary cortisol after 1-mg DST is inferior to serum cortisol after 1-mg DST in the diagnostic performance and diagnostic accuracy, it can be used as a low-invasive screening test with superior specificity

Long-term treatment options for postmenopausal osteoporosis: results of recent clinical studies of Denosumab

Modern medications for osteoporosis (bisphosphonates, denosumab, teriparatide) are well-tolerated drugs, which can significantly lower vertebral and non-vertebral fracture risk according to prospective and observational studies in up to 10-year period. Certain drugs (denosumab, teriparatide) are active only during the treatment period and do not prevent bone loss and fracture risk after discontinuation, while such protective effect is observed in bisphosphonates. Despite impressive success of continuous 10-year denosumab treatament of severe osteoporosis, some of the recently published data suggest that vertebral fracture incidence is increased after treatment discontinuation, along with multiple vertebral fracture incidence, especially in patients with previous fractures. Issues of osteoporosis treatment duration, sequential use of osteoporosis drugs and criteria for treatment discontinuation are now in focus of attention. European Medicines Agency (EMA) and European Calcified Tissue Society (ECTS) considered these issues in 2017. ЕМА considered fractures after denosumab discontinuation as a natural disease course and did not recommend any changes in product instruction. The main conclusion of ECTS is that the possibility of multiple fractures development after denosumab discontinuation exists, however, there is still not enough firm evidence, as well as effective countermeasures. Clinicians and patients should be aware of potential risk. Both EMA and ECTS suggest considering denosumab treatment or discontinuation after 5-year treatment period or possibly replacing with bisphosphonates. Recent data suggest that prolonged osteoporosis treatment can be done in accordance with the concept of treatment until target goal (for example, achievement of femoral T-score -2.0SD and higher). In our review, we focus on recent data concerning the issues stated above. This topic was also discussed on Russian Osteoporosis Association (ROA) expert meeting in Saint Petersburg on 24 may 2018, chaired by ROA president, professor Olga Lesnyak and Columbia University professor, J.P. Bilezikian. As a result, an Expert Council resolution was written and introduced in the article