Use of teriparatide in treatment of severe osteoporosis in geriatric practice: a clinical case review

Elderly and senile people are characterized by a high prevalence of osteoporosis, which, in turn, increases the risk of fractures, including the repeated ones. Fractures in osteoporosis are an extremely unfavorable complication of the disease, leading to catastrophic consequences in old age. The prevalence of osteoporotic fractures progressively increases with age. At present, the cumulative frequency of hip fractures in women over 80 is about 30%. The proportion of vertebral fractures in women older than 80 years is up to 40% of all vertebral osteoporotic fractures. Despite the tremendous successes achieved in the diagnosis and treatment of osteoporosis, the disease itself and related fractures remain a serious medical, economic and social problem. Prevention of recurrent fractures in geriatric patients is a system of preventive, rehabilitative and therapeutic measures aimed at reducing the risk of falls, choosing an effective therapy, and reducing the risk of recurring fractures. A serious problem in the treatment of osteoporosis in older people is the inefficiency of the antiresorptive therapy due to an age-related decrease in bone formation. There are frequent cases of a continuing decrease in bone density, the occurrence of repeated fractures during ongoing therapy of osteoporosis. Often the therapy of choice in this case is bone-anabolic therapy with teriparatide, which allows one to achieve good results in the accumulation of bone mineral density. In this article, we will present the clinical case of an elderly patient with severe osteoporosis, in which teriparatide became the drug of choice

A New Approach to Overcome Insulin Resistance in Patients with Impaired Glucose Tolerance: The Results of a Multicenter, Double-Blind, Placebo-Controlled, Randomized Clinical Trial of Efficacy and Safety of Subetta

Impaired glucose tolerance (IGT) is a common carbohydrate metabolism disorder world-wide. To evaluate the efficacy and safety of 12-week Subetta therapy in correcting 2-h plasma glucose in patients with IGT, a multicenter, double-blind, placebo-controlled, randomized clinical trial was performed. Derived by technological treatment of antibodies to insulin receptor β-subunit and endothelial NO synthase, Subetta increases the sensitivity of insulin receptors by activating the insulin signaling pathway. Oral glucose tolerance test (OGTT), fasting plasma glucose (FPG), and glycated hemoglobin (HbA1c) were examined at screening, after 4 and 12 weeks. In Per Protocol population, 2-h plasma glucose in the Subetta group decreased by 2.05 ± 2.11 mmol/L (versus 0.56 ± 2.55 mmol/L in the Placebo group) after 12 weeks. The difference between the two groups was 1.49 ± 2.33 mmol/L (p < 0.0001). After 12 weeks, 65.2% of patients had 2-h plasma glucose <7.8 mmol/L. FPG remained almost unchanged. HbA1c tended to decrease. The number of adverse events did not differ in both groups. Subetta treatment is beneficial for patients with IGT; it also prevents progression of carbohydrate metabolism disorders

Association of Insulin Resistance, Arterial Stiffness and Telomere Length in Adults Free of Cardiovascular Diseases.

Chronic inflammation and oxidative stress might be considered the key mechanisms of aging. Insulin resistance (IR) is a phenomenon related to inflammatory and oxidative stress. We tested the hypothesis that IR may be associated with cellular senescence, as measured by leukocyte telomere length (LTL), and arterial stiffness (core feature of arterial aging), as measured by carotid-femoral pulse wave velocity (c-f PWV).The study group included 303 subjects, mean age 51.8 ±13.3 years, free of known cardiovascular diseases and regular drug consumption. For each patient, blood pressure was measured, blood samples were available for biochemical parameters, and LTL was analyzed by real time q PCR. C-f PWV was measured with the help of SphygmoCor. SAS 9.1 was used for statistical analysis.Through multiple linear regression analysis, c-f PWV is independently and positively associated with age (p = 0.0001) and the homeostasis model assessment of insulin resistance (HOMA-IR; p = 0.0001) and independently negatively associated with LTL (p = 0.0378). HOMA-IR seems to have a stronger influence than SBP on arterial stiffness. In all subjects, age, HOMA-IR, LTL, and SBP predicted 32% of the variance in c-f PWV. LTL was inversely associated with HOMA-IR (p = 0.0001) and age (p = 0.0001). In all subjects, HOMA-IR, age, sex, and SBP predicted 16% of the variance in LTL.These data suggest that IR is associated with cell senescence and arterial aging and could, therefore, become the main target in preventing accelerated arterial aging, besides blood pressure control. Research in telomere biology may reveal new ways of estimating cardiovascular aging and risk

Atorvastatin therapy modulates telomerase activity in patients free of atherosclerotic cardiovascular diseases

Background— Telomerase activity (TA) is considered as the biomarker for cardiovascular aging and cardiovascular diseases. Recent studies suggest a link between statins and telomere biology that may be explained by anti-inflammatory actions of statins and their positive effect on TA. Until now this effect has not been investigated in prospective randomized studies.We hypothesized that 12 months of atorvastatin therapy increased TA in peripheral blood mononuclear cells.Methods—In a randomized, placebo-controlled study 100 hypercholesterolemic patients, aged 35–75 years, free of known cardiovascular diseases and diabetes mellitus type 2 received 20 mg of atorvastatin daily or placebo for 12 months. TA was measured by quantitative polymerase chain reaction.Results—At study end 82 patients had sufficient peripheral blood mononuclear cells needed for longitudinal analysis. TA expressed as natural logarithms changed from 0.46±0.05 to 0.68±0.06 (p=0.004) in the atorvastatin group and from 0.67±0.06 to 0.60±0.07 (P=0.477) in the control group. In multiple regression analysis, atorvastatin therapy was the only independent predictor (p=0.05) of the changes in TA independently of markers of chronic inflammation and oxidative stress. Atorvastatin therapy was associated with increases in IL-6 within the normal range and a tendency towards reductionin blood urea.Conclusions—These initial observations suggest atorvastatin can act as telomerase activator and potentially as effective geroprotector

Multiple linear regression analysis of LTL (dependent variable) with age, sex, SBP, HOMA-IR as independent variables.

<p>Abbreviations: Error SS: error of sum of squares; HOMA-IR, homeostasis model assessment of insulin resistance; LTL, leukocyte telomere length; SBP, systolic blood pressure; S.E.: standard error; <b>Total SS: total sum of squares;</b> Type III SS: type III sum of squares</p><p>Multiple linear regression analysis of LTL (dependent variable) with age, sex, SBP, HOMA-IR as independent variables.</p

Multiple linear regression analysis of c-f PWV (dependent variable) on age, SBP, LTL, HOMA-IR as independent variables.

<p>Abbreviations: c-f PWV, carotid-femoral pulse wave velocity; Error SS: error of sum of squares; HOMA-IR, homeostasis model assessment of insulin resistance; LTL, leukocyte telomere length; SBP, systolic blood pressure; S.E.: standard error; <b>Total SS: total sum of squares;</b> Type III SS:type III sum of squares.</p><p>Multiple linear regression analysis of c-f PWV (dependent variable) on age, SBP, LTL, HOMA-IR as independent variables.</p

Clinical and metabolic characteristics of the study participants in the total group and according to HOMA-IR.

<p><b>Abbreviations:</b> BMI: body mass index; c-f PWV: carotid-femoral pulse wave velocity; DBP: diastolic blood pressure; FG: fasting glucose; HbA_1c: glycosylated hemoglobin; HOMA-IR: homeostasis model assessment of insulin resistance; LTL: leukocyte telomere length; SBP: systolic blood pressure; TA: telomerase activity; 2h OGTT:2-h glucose level following the oral glucose tolerance test; P-value: p between HOMA-IR ≤ 2.5 and HOMA-IR >2.5 groups</p><p>Clinical and metabolic characteristics of the study participants in the total group and according to HOMA-IR.</p

Telomere length and vascular wall in patients with Type 2 Diabetes Mellitus

Aim. To study the relationship between changes in the artery structure and function and peripheral lymphocyte telomere length in patients with type 2 diabetes mellitus (DM2). Materials and methods. A total of 50 patients with T2DM and without clinical manifestations of cardiovascular disease (CVD) were included in the study; the control group consisted of 49 people. The following tests were conducted for all study participants: carbohydrate metabolism evaluation, carotid artery duplex scan to measure intima?media complex thickness (IMT) and to determine the presence of atherosclerotic plaques, carotid?femoral pulse wave velocity (PWV) measurement and lymphocyte telomere length measurement. Results. The vascular changes were more pronounced in patients with T2DM than in controls. The telomeres were shorter in patients with T2DM than in those without diabetes (9.53?0.1 vs 9.86?0.1, p=0.033). The participants were divided according to the telomere length. Among patients with T2DM, there were significant differences in the condition of the vascular wall [PWV: 10.58?0.1 m/s in patients with ?long? telomeres and 15.08?1.3 m/s in patients with ?short? telomeres; IMT: 0.80?0.09 mm in patients with ?long? telomeres and 0.87?0.05 mm in patients with ?short? telomeres (p=0.024)]. There were no significant differences in the arterial structure between the patient and control groups with ?long? telomeres [PWV: 10.58?0.1 m/s vs 10.5?0.5 m/s (p=0.913); IMT: 0.080?0.09 mm vs 0.73?0.03 mm (p=0.12). However, there were significant differences in the vascular wall condition between the patient and control groups with ?short? telomeres [PWV: 15.08?1.3 m/s vs, 10.7?0.5 m/s (p=0.015); IMT: 0.87?0.1 vs 0.78?0.1 (p=0.03)]. Conclusions. The signs of vascular ageing were more pronounced in patients with T2DM than in controls. However, despite diabetes, vascular changes were minimal in patients with ?long? lymphocyte telomeres, comparable with the state of the vascular walls in healthy individuals. Thus, enhanced lymphocyte telomere length may have a protective effect on the vascular wall and may prevent damage from carbohydrate metabolism disorders