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

Results of screening for antibodies to varicella-zoster virus in healthcare workers of a multidisciplinary hospital in Moscow

Introduction. Given the unfavorable epidemic situation with chickenpox and shingles in Russia, there is a high risk of virus introduction and spread in healthcare settings, including among medical staff who are not immune to varicella zoster virus (VZV). The objective of this study is to assess the immunity of employees of a multidisciplinary hospital in Moscow to VZV. Materials and methods. A selective screening study was carried out. Venous blood serum samples were taken from 1546 hospital employees as material for detection of IgG antibodies to VZV antigens using a commercial solid-phase enzyme immunoassay (ELISA) test system "Vecto VZV-IgG". All employees were questioned to obtain information about their infectious and vaccine history in relation to VZV. Results and discussion. Screening for antibodies to VZV in the hospital workers revealed that 6.3% of those workers are not immune to VZV. The proportion of seronegative individuals was the highest (12.6 ± 2.4%) in the age group of 29 years and younger. VZV seronegative healthcare workers were found in various departments, but the presence of non-immune individuals among the staff of the obstetrics and gynecology departments (6.5%) is of epidemiologic concern. The results of the survey showed that documented data on infection and vaccination history cannot be used to assess the protection of healthcare workers against VZV infection. Conclusion. The results of serologic screening for antibodies to VZV made it possible to identify a significant number of susceptible employees of the multidisciplinary hospital. In order to prevent the formation of multiple epidemic foci of varicella in medical organizations, it is advisable to include anti-VZV testing of medical staff in the state prevention programs with subsequent vaccination of non-immune individuals

Acute and chronic pain in vertebral fractures as systemic osteoporosis complication. Literature review

A literature review is devoted to acute and chronic pain mechanisms in vertebral fractures complicating osteoporosis. The data of pharmacological and non-pharmacological methods of pain relief for vertebral bodies fractures, which precede the pathogenetic therapy of osteoporosis or could be combined with it

Insights into the late Holocene vegetation history of the East European forest-steppe: case study Sudzha (Kursk region, Russia)

Today, the East European forest-steppe is an agricultural landscape with very few remains of its former natural vegetation. The history of the transformation from natural vegetation to a human-made landscape in the area of Sudzha (Kursk region, Russia) is studied here. We compare the off-site pollen record Sudzha with three on-site pollen records obtained from the archaeological site Kurilovka-2. The sediment core Sudzha covering the last 2,500 years was taken from an oxbow lake in an area with archaeological sites of the early Slavonic period (3rd–8th centuries ce). The Sudzha pollen record indicates dominance of broadleaf forests and meadow steppes in the area from 2,500 to 200 cal year bp with two major settlement phases one between ~ 2,000 and 1,600 cal year bp (~ 50 bce to 350 ce) and the other between 1,100 and 600 cal year bp (850 and 1350 ce) followed by a total deforestation and transformation to an agricultural landscape over the last 200–300 years. Similar changes in the last 300–400 years are indicated by the three on-site pollen records. It is noteworthy, however, that the record Sudzha does not provide an intensive signal of human impact during the 5th–8th centuries ce. This points to a quite restricted spatial influence of the Early Slavonic settlements on the vegetation, leading to a relatively low contribution of palynological anthropogenic indicators to the regional pollen rain signal

Odanacatib for the treatment of postmenopausal osteoporosis : Results of the LOFT multicentre, randomised, double-blind, placebo-controlled trial and LOFT Extension study

Background Odanacatib, a cathepsin K inhibitor, reduces bone resorption while maintaining bone formation. Previous work has shown that odanacatib increases bone mineral density in postmenopausal women with low bone mass. We aimed to investigate the efficacy and safety of odanacatib to reduce fracture risk in postmenopausal women with osteoporosis. Methods The Long-term Odanacatib Fracture Trial (LOFT) was a multicentre, randomised, double-blind, placebo-controlled, event-driven study at 388 outpatient clinics in 40 countries. Eligible participants were women aged at least 65 years who were postmenopausal for 5 years or more, with a femoral neck or total hip bone mineral density T-score between −2·5 and −4·0 if no previous radiographic vertebral fracture, or between −1·5 and −4·0 with a previous vertebral fracture. Women with a previous hip fracture, more than one vertebral fracture, or a T-score of less than −4·0 at the total hip or femoral neck were not eligible unless they were unable or unwilling to use approved osteoporosis treatment. Participants were randomly assigned (1:1) to either oral odanacatib (50 mg once per week) or matching placebo. Randomisation was done using an interactive voice recognition system after stratification for previous radiographic vertebral fracture, and treatment was masked to study participants, investigators and their staff, and sponsor personnel. If the study completed before 5 years of double-blind treatment, consenting participants could enrol in a double-blind extension study (LOFT Extension), continuing their original treatment assignment for up to 5 years from randomisation. Primary endpoints were incidence of vertebral fractures as assessed using radiographs collected at baseline, 6 and 12 months, yearly, and at final study visit in participants for whom evaluable radiograph images were available at baseline and at least one other timepoint, and hip and non-vertebral fractures adjudicated as being a result of osteoporosis as assessed by clinical history and radiograph. Safety was assessed in participants who received at least one dose of study drug. The adjudicated cardiovascular safety endpoints were a composite of cardiovascular death, myocardial infarction, or stroke, and new-onset atrial fibrillation or flutter. Individual cardiovascular endpoints and death were also assessed. LOFT and LOFT Extension are registered with ClinicalTrials.gov (number NCT00529373) and the European Clinical Trials Database (EudraCT number 2007-002693-66). Findings Between Sept 14, 2007, and Nov 17, 2009, we randomly assigned 16 071 evaluable patients to treatment: 8043 to odanacatib and 8028 to placebo. After a median follow-up of 36·5 months (IQR 34·43–40·15) 4297 women assigned to odanacatib and 3960 assigned to placebo enrolled in LOFT Extension (total median follow-up 47·6 months, IQR 35·45–60·06). In LOFT, cumulative incidence of primary outcomes for odanacatib versus placebo were: radiographic vertebral fractures 3·7% (251/6770) versus 7·8% (542/6910), hazard ratio (HR) 0·46, 95% CI 0·40–0·53; hip fractures 0·8% (65/8043) versus 1·6% (125/8028), 0·53, 0·39–0·71; non-vertebral fractures 5·1% (412/8043) versus 6·7% (541/8028), 0·77, 0·68–0·87; all p<0·0001. Combined results from LOFT plus LOFT Extension for cumulative incidence of primary outcomes for odanacatib versus placebo were: radiographic vertebral fractures 4·9% (341/6909) versus 9·6% (675/7011), HR 0·48, 95% CI 0·42–0·55; hip fractures 1·1% (86/8043) versus 2·0% (162/8028), 0·52, 0·40–0·67; non-vertebral fractures 6·4% (512/8043) versus 8·4% (675/8028), 0·74, 0·66–0·83; all p<0·0001. In LOFT, the composite cardiovascular endpoint of cardiovascular death, myocardial infarction, or stroke occurred in 273 (3·4%) of 8043 patients in the odanacatib group versus 245 (3·1%) of 8028 in the placebo group (HR 1·12, 95% CI 0·95–1·34; p=0·18). New-onset atrial fibrillation or flutter occurred in 112 (1·4%) of 8043 patients in the odanacatib group versus 96 (1·2%) of 8028 in the placebo group (HR 1·18, 0·90–1·55; p=0·24). Odanacatib was associated with an increased risk of stroke (1·7% [136/8043] vs 1·3% [104/8028], HR 1·32, 1·02–1·70; p=0·034), but not myocardial infarction (0·7% [60/8043] vs 0·9% [74/8028], HR 0·82, 0·58–1·15; p=0·26). The HR for all-cause mortality was 1·13 (5·0% [401/8043] vs 4·4% [356/8028], 0·98–1·30; p=0·10). When data from LOFT Extension were included, the composite of cardiovascular death, myocardial infarction, or stroke occurred in significantly more patients in the odanacatib group than in the placebo group (401 [5·0%] of 8043 vs 343 [4·3%] of 8028, HR 1·17, 1·02–1·36; p=0·029, as did stroke (2·3% [187/8043] vs 1·7% [137/8028], HR 1·37, 1·10–1·71; p=0·0051). Interpretation Odanacatib reduced the risk of fracture, but was associated with an increased risk of cardiovascular events, specifically stroke, in postmenopausal women with osteoporosis. Based on the overall balance between benefit and risk, the study's sponsor decided that they would no longer pursue development of odanacatib for treatment of osteoporosis