Factors influencing bone mineral density in postpartum women

Background: Osteopenia is a common condition. Therefore, identification of groups for prevention of osteoporosis and restoration of bone mineral density (BMD) remains relevant. Aim: to assess the factors contributing to development of osteopenia in puerperas. Methods: prospective cross-sectional study. We examined 112 patients aged 20-35, 3-5 days after delivery. To assess possible factors for BMD decrease, we analyzed medical history, lifestyle, nutrition, anthropometric data, obstetric and gynecological history, and pregnancy course. We also assessed serum levels of 25-hydroxycalciferol (25-OH-D) and PTH. BMD was measured by dual energy x-ray osteodensitometry. We considered Z-score from -1 to -2.5SD as osteopenia, below -2.5 SD-as osteoporosis. Results: based on Z-score values, two groups were formed: 1 (n=70) - puerperas with osteopenia, 2 (n=42) - puerperas with normal BMD. In the first group, osteopenia in the distal radius was observed in 48%, in the lumbar spine in 16% and in the proximal femur in 36%. Influence of the following possible factors in group 1 was established: BMI in 15-20 years 18 kg/m2 (p0.013), BMI 25 kg/m2 (p0.018), 25-OH-D less than 25 ng / ml (p 0.0018), calcium intake less than 800 mg/day (p0.041). Menstrual disorders (p0.052) and preeclapsia (p 0.042) affected lumbar spine BMD. In group 1, vitamin D deficiency was detected in 82% of women, 18% showed vitamin D insufficiency; in group 2, vitamin D deficiency was found in 16%, deficiency in 70%, in 14% vitamin D was normal. In women with a combination of factors such as BMI 18 kg/m; calcium intake lower than 800 mg/day, menstrual cycle disorders, vitamin D deficiency - osteopenia in the distal radius occured 11 times more often (OR=11,47059; CI 95%=[4,0326; 32,627]). Conclusion: most significant impact on BMD decrease in puerperas can be expected if patient has the following risk factors: BMI18 kg/m2; 25-OH- D25 ng/ml ; nutrition with calcium intake 800 mg per day, preeclampsia. Combination of these factors may increase the risk of osteopenia in the distal radius

Individualized versus conventional ovarian stimulation for in vitro fertilization: a multicenter, randomized, controlled, assessor-blinded, phase 3 noninferiority trial

Objective To compare the efficacy and safety of follitropin delta, a new human recombinant FSH with individualized dosing based on serum antimüllerian hormone (AMH) and body weight, with conventional follitropin alfa dosing for ovarian stimulation in women undergoing IVF. Design Randomized, multicenter, assessor-blinded, noninferiority trial (ESTHER-1). Setting Reproductive medicine clinics. Patient(s) A total of 1,329 women (aged 18â40 years). Intervention(s) Follitropin delta (AMH <15 pmol/L: 12 μg/d; AMH â¥15 pmol/L: 0.10â0.19 μg/kg/d; maximum 12 μg/d), or follitropin alfa (150 IU/d for 5 days, potential subsequent dose adjustments; maximum 450 IU/d). Main Outcomes Measure(s) Ongoing pregnancy and ongoing implantation rates; noninferiority margins â8.0%. Result(s) Ongoing pregnancy (30.7% vs. 31.6%; difference â0.9% [95% confidence interval (CI) â5.9% to 4.1%]), ongoing implantation (35.2% vs. 35.8%; â0.6% [95% CI â6.1% to 4.8%]), and live birth (29.8% vs. 30.7%; â0.9% [95% CI â5.8% to 4.0%]) rates were similar for individualized follitropin delta and conventional follitropin alfa. Individualized follitropin delta resulted in more women with target response (8â14 oocytes) (43.3% vs. 38.4%), fewer poor responses (fewer than four oocytes in patients with AMH <15 pmol/L) (11.8% vs. 17.9%), fewer excessive responses (â¥15 or â¥20 oocytes in patients with AMH â¥15 pmol/L) (27.9% vs. 35.1% and 10.1% vs. 15.6%, respectively), and fewer measures taken to prevent ovarian hyperstimulation syndrome (2.3% vs. 4.5%), despite similar oocyte yield (10.0 ± 5.6 vs. 10.4 ± 6.5) and similar blastocyst numbers (3.3 ± 2.8 vs. 3.5 ± 3.2), and less gonadotropin use (90.0 ± 25.3 vs. 103.7 ± 33.6 μg). Conclusion(s) Optimizing ovarian response in IVF by individualized dosing according to pretreatment patient characteristics results in similar efficacy and improved safety compared with conventional ovarian stimulation. Clinical Trial Registration Number NCT01956110

Magnetic resonance imaging for non-invasive diagnosis of various forms of endometriosis in women with infertility

BACKGROUND: Endometriosis is one of the most common causes of infertility, affecting approximately 6%10% of women of reproductive age. For many decades, laparoscopic surgery has been considered the gold standard for diagnosing various forms of endometriosis. However, diagnostic laparoscopy, despite its widespread use, is an invasive and expensive procedure with certain risks. Current scientific literature increasingly shows that the methods of radiological diagnosis (ultrasound and magnetic resonance imaging [MRI]) are the main and most promising for verification of endometriosis. The advantages of MRI over ultrasound are multiplanar images, high tissue contrast, and smaller size of detectable heterotopias. AIM: To assessing the sensitivity and specificity of MRI for diagnosing different forms of endometriosis. METHODS: A retrospective analysis of the medical histories and instrumental studies of 129 women of reproductive age (mean age of the participants was 30.54.6 years) with a clinical diagnosis of infertility and suspected genital endometriosis was conducted. At the first stage of the study, the patients underwent a comprehensive MRI with one-stage magnetic resonance hysterosalpingography to assess the pelvis and tubal patency. Further, laparoscopic surgery (LS) was performed to confirm/refute the diagnosis of genital endometriosis, provide surgical treatment, or further search for possible causes of infertility. The results obtained with MRI and LS were compared, and the sensitivity and specificity of MRI for diagnosing external and internal genital endometriosis were assessed. RESULTS: According to the data obtained, the specificity of MRI for diagnosing peritoneal endometriosis was 74% (95% confidence interval [CI], 57%85%), and the sensitivity was 94% (95% CI, 87%99%). Diagnostic accuracy of the technique was 86% (95% CI, 79%91%). The most frequent localization of endometrioid heterotopias was retrocervical (41%). The specificity of this technique for diagnosing endometrioid ovarian cysts was 92% (95% CI, 82%97%), and the sensitivity amounted for 98% (95% CI, 90%100%). Diagnostic accuracy of the technique was 94% (95% CI, 88%96%). The specificity and sensitivity of MRI for the diagnosis of adenomyosis were 96% (95% CI, 92%99%) and 99% (95% CI, 87%100%), respectively. Diagnostic accuracy of the technique was 97% (95% CI, 93%99%). Our results were consistent with the literature data on the accuracy of MRI for diagnosing endometriosis. CONCLUSIONS: Based on the results, MRI is a promising non-invasive method for diagnosing various forms of endometriosis. The performance of a comprehensive MRI allows obtaining sufficiently accurate information about the condition of the pelvic organs, detecting the manifestations of genital endometriosis, and reducing the time for examining women with infertility

A comparison of the clinical outcomes of induced and spontaneous labour in patients with gestational diabetes

Aim. To evaluate the clinical outcomes of induced and spontaneous labour in patients with gestational diabetes (GD). Materials and methods. This retrospective cohort study conducted at the Federal Almazov Northwest Medical Research Centre included 251 patients with GD who had given birth during 2014. The patients were divided into the following two groups: one included 210 patients who were treated with diet and the other included 41 patients who were treated with insulin. Clinical outcomes were compared between patients who had induced (n = 43) or spontaneous (n = 188) labour. Results. Complications of labour, such as dysthyroidism and uterine inertia, were significantly more common (p 0. 05) in induced labour patients than in those who had spontaneous labour (16. 3 vs. 3. 2% and 7% vs. 0%, respectively). Fetal distress occurred in 10. 6% and 9. 3% of patients during spontaneous and induced labour, respectively. The frequency of ceasarean section after induced labour was not significantly greater than that among patients who had spontaneous labour. Conclusion. Delivery at 38 to 39 weeks in women with GD has led to an increase in the rate of birth complications, such as uterine inertia and dysthyroidism. Gestational age cannot be considered as a sufficient indicator of labour induction at full-term in the absence of foetus distress or poor maternal glycemic control

Antibody to Marinobufagenin Reverses Placenta-Induced Fibrosis of Umbilical Arteries in Preeclampsia

Background: Previous studies implicated cardiotonic steroids, including Na/K-ATPase inhibitor marinobufagenin (MBG), in the pathogenesis of preeclampsia (PE). Immunoneutralization of heightened MBG by Digibind, a digoxin antibody, reduces blood pressure (BP) in patients with PE, and anti-MBG monoclonal antibody lessens BP in a rat model of PE. Recently, we demonstrated that MBG induces fibrosis in cardiovascular tissues via a mechanism involving inhibition of Fli-1, a nuclear transcription factor and a negative regulator of collagen-1 synthesis. Objectives and Methods: We hypothesized that in PE, elevated placental MBG levels are associated with development of fibrosis in umbilical arteries. Eleven patients with PE (mean BP 124 ± 4 mmHg; age 29 ± 2 years; 39 weeks gest. age) and 10 gestational age-matched normal pregnant subjects (mean BP 92 ± 2 mmHg; controls) were enrolled in the clinical study. Results: PE was associated with a higher placental (0.04 ± 0.01 vs. 0.49 ± 0.11 pmol/g; p < 0.01) and plasma MBG (0.5 ± 0.1 vs. 1.6 ± 0.5 nmol/L; p < 0.01), lower Na/K-ATPase activity in erythrocytes (2.7 ± 0.2 vs. 1.5 ± 0.2 µmol Pi/mL/hr; p < 0.01), 9-fold decrease of Fli-1 level and 2.5-fold increase of collagen-1 in placentae (p < 0.01) vs. control. Incubation of umbilical arteries from control patients with 1 nmol/L MBG was associated with four-fold decrease in Fli-1 level and two-fold increase in collagen-1 level vs. those incubated with placebo (p < 0.01), i.e., physiological concentration of MBG mimicked effect of PE in vitro. Collagen-1 abundance in umbilical arteries from PE patients was 4-fold higher than in control arteries, and this PE-associated fibrosis was reversed by monoclonal anti-MBG antibody ex vivo. Conclusion: These results demonstrate that elevated placental MBG level is implicated in the development of fibrosis of the placenta and umbilical arteries in PE

Effect of once-yearly zoledronic acid on the spine and hip as measured by quantitative computed tomography: results of the HORIZON Pivotal Fracture Trial.

Changes in bone mineral density and bone strength following treatment with zoledronic acid (ZOL) were measured by quantitative computed analysis (QCT) or dual-energy X-ray absorptiometry (DXA). ZOL treatment increased spine and hip BMD vs placebo, assessed by QCT and DXA. Changes in trabecular bone resulted in increased bone strength. INTRODUCTION: To investigate bone mineral density (BMD) changes in trabecular and cortical bone, estimated by quantitative computed analysis (QCT) or dual-energy X-ray absorptiometry (DXA), and whether zoledronic acid 5 mg (ZOL) affects bone strength. METHODS: In 233 women from a randomized, controlled trial of once-yearly ZOL, lumbar spine, total hip, femoral neck, and trochanter were assessed by DXA and QCT (baseline, Month 36). Mean percentage changes from baseline and between-treatment differences (ZOL vs placebo, t-test) were evaluated. RESULTS: Mean between-treatment differences for lumbar spine BMD were significant by DXA (7.0%, p < 0.01) and QCT (5.7%, p < 0.0001). Between-treatment differences were significant for trabecular spine (p = 0.0017) [non-parametric test], trabecular trochanter (10.7%, p < 0.0001), total hip (10.8%, p < 0.0001), and compressive strength indices at femoral neck (8.6%, p = 0.0001), and trochanter (14.1%, p < 0.0001). CONCLUSIONS: Once-yearly ZOL increased hip and spine BMD vs placebo, assessed by QCT vs DXA. Changes in trabecular bone resulted in increased indices of compressive strength

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