<i>Lactobacillus reuteri</i> reduces bone loss in older women with low bone mineral density:a randomized, placebo-controlled, double-blind, clinical trial

Background: The importance of the gut microbiome for bone metabolism in mice has recently been demonstrated, but no studies are available in humans. Lactobacillus reuteri ATCCPTA 6475 (L. reuteri 6475) has been reported to increase bone mineral density (BMD) in mice but its effect on the human skeleton is unknown. The objective of this trial was to investigate if L. reuteri 6475 affects bone loss in older women with low BMD. Methods: In this double‐blind, placebo‐controlled study, women from the population who were 75 to 80 years old and had low BMD were randomized to orally receive 1010 colony‐forming units of L. reuteri 6475 daily or placebo. The predefined primary end‐point was relative change after 12 months in tibia total volumetric BMD (vBMD). Results: Ninety women were included and 70 completed the study. L. reuteri 6475 reduced loss of total vBMD compared to placebo both in the intention‐to‐treat (ITT) analysis [−0.83% (95% confidence interval [CI], −1.47 to −0.19%) vs. −1.85% (95% CI, −2.64 to −1.07%); mean difference 1.02% (95% CI, 0.02–2.03)] and per protocol analysis [−0.93% (95% CI, −1.45 to −0.40) vs. −1.86% (95% CI, −2.35 to −1.36); mean difference 0.93% (95% CI, 0.21–1.65)]. In general, similar but smaller effects were observed in the secondary bone variable outcomes, but these differences did not reach statistical significance in the ITT population. Adverse events did not differ between groups. Conclusions: Supplementation with L. reuteri 6475 should be further explored as a novel approach to prevent age‐associated bone loss and osteoporosis

Patients with prostate cancer and androgen deprivation therapy have increased risk of fractures—a study from the Fractures and Fall Injuries in the Elderly Cohort (FRAILCO)

Summary Osteoporosis is a common complication of androgen deprivation therapy (ADT). In this large Swedish cohort study consisting of a total of nearly 180,000 older men, we found that those with prostate cancer and ADT have a significantly increased risk of future osteoporotic fractures. Introduction: Androgen deprivation therapy (ADT) in patients with prostate cancer is associated to increased risk of fractures. In this study, we investigated the relationship between ADT in patients with prostate cancer and the risk of incident fractures and non-skeletal fall injuries both compared to those without ADT and compared to patients without prostate cancer. Methods: We included 179,744 men (79.1 ± 7.9 years (mean ± SD)) from the Swedish registry to which national directories were linked in order to study associations regarding fractures, fall injuries, morbidity, mortality and medications. We identified 159,662 men without prostate cancer, 6954 with prostate cancer and current ADT and 13,128 men with prostate cancer without ADT. During a follow-up of approximately 270,300 patient-years, we identified 10,916 incident fractures including 4860 hip fractures. Results: In multivariable Cox regression analyses and compared to men without prostate cancer, those with prostate cancer and ADT had increased risk of any fracture (HR 95% CI 1.40 (1.28–1.53)), hip fracture (1.38 (1.20–1.58)) and MOF (1.44 (1.28–1.61)) but not of non-skeletal fall injury (1.01 (0.90–1.13)). Patients with prostate cancer without ADT did not have increased risk of any fracture (0.97 (0.90–1.05)), hip fracture (0.95 (0.84–1.07)), MOF (1.01 (0.92–1.12)) and had decreased risk of non-skeletal fall injury (0.84 (0.77–0.92)). Conclusions: Patients with prostate cancer and ADT is a fragile patient group with substantially increased risk of osteoporotic fractures both compared to patients without prostate cancer and compared to those with prostate cancer without ADT. We believe that this must be taken in consideration in all patients with prostate cancer already at the initiation of ADT

A new and efficient approach to time-dependent density-functional perturbation theory for optical spectroscopy

Using a super-operator formulation of linearized time-dependent density-functional theory, the dynamical polarizability of a system of interacting electrons is given a matrix continued-fraction representation whose coefficients can be obtained from the non-symmetric block-Lanczos method. The resulting algorithm allows for the calculation of the {\em full spectrum} of a system with a computational workload which is only a few times larger than that needed for {\em static} polarizabilities within time-independent density-functional perturbation theory. The method is demonstrated with the calculation of the spectrum of benzene, and prospects for its application to the large-scale calculation of optical spectra are discussed.Comment: 4 pages, 2 figure

Advancing maternal age is associated with lower bone mineral density in young adult male offspring

Summary Advancing maternal age has been related to increased risk of fetal death and morbidity, as well as higher fracture risk during childhood, in the offspring. In the present study, we demonstrate that advancing maternal age is independently associated with reduced bone mass in the young adult male offspring. Introduction In Sweden the maternal age in both primi- and multipara mothers has steadily increased during the last three decades. It has been previously reported that advancing maternal age increases the risk of fetal death, but also of morbidity in the offspring, such as chromosome abnormalities, leukemia, diabetes mellitus type 1, and schizophrenia. Whether or not maternal age influences peak bone mass has not been reported. The aim of the present study was to investigate whether a high maternal age was associated with lower peak bone mass, as measured using DXA in a large cohort of male offspring [the Gothenburg Osteoporosis and Obesity Determinants study (GOOD)]. Methods Through the Swedish multi-generation register, we identified the mothers of 1,009 GOOD study subjects. From the Swedish medical birth register detailed information about the medical circumstances at the time of child birth were obtained, including maternal and offspring anthropometrics (birth height and weight), maternal age, and smoking habits, parity and length of pregnancy. Results Maternal age was inversely correlated to areal BMD (aBMD) at the total body (r =−0.07, p = 0.03) and the lumbar spine (r =−0.09, p < 0.01). Using a linear regression model (with covariates including current physical activity, smoking, calcium intake, weight, present height and birth height, total body lean and fat mass in the offspring, and length of pregnancy), we found that maternal age negatively independently predicted lumbar spine aBMD (β =−0.08, p < 0.01) in the male offspring. Conclusions In conclusion, our results suggest that advancing maternal age could negatively affect bone mass in young adult men

Hip fracture risk and safety with alendronate treatment in the oldest-old

Background. There is high evidence for secondary prevention of fractures, including hip fracture, with alendronate treatment, but alendronate’s efficacy to prevent hip fractures in the oldest-old (≥80 years old), the population with the highest fracture risk, has not been studied. Objective. To investigate whether alendronate treatment amongst the oldest-old with prior fracture was related to decreased hip fracture rate and sustained safety. Methods. Using a national database of men and women undergoing a fall risk assessment at a Swedish healthcare facility, we identified 90 795 patients who were 80 years or older and had a prior fracture. Propensity score matching (four to one) was then used to identify 7844 controls to 1961 alendronate-treated patients. The risk of incident hip fracture was investigated with Cox models and the interaction between age and treatment was investigated using an interaction term. Results. The case and control groups were well balanced in regard to age, sex, anthropometrics and comorbidity. Alendronate treatment was associated with a decreased risk of hip fracture in crude (hazard ratio (HR) 0.62 (0.49–0.79), P < 0.001) and multivariable models (HR 0.66 (0.51–0.86), P < 0.01). Alendronate was related to reduced mortality risk (HR 0.88 (0.82–0.95) but increased risk of mild upper gastrointestinal symptoms (UGI) (HR 1.58 (1.12–2.24). The alendronate association did not change with age for hip fractures or mild UGI. Conclusion. In old patients with prior fracture, alendronate treatment reduces the risk of hip fracture with sustained safety, indicating that this treatment should be considered in these high-risk patient

Fall risk assessment predicts fall-related injury, hip fracture, and head injury in older adults

Objectives To investigate the role of a fall risk assessment, using the Downton Fall Risk Index (DFRI), in predicting fall‐related injury, fall‐related head injury and hip fracture, and death, in a large cohort of older women and men residing in Sweden. Design Cross sectional observational study. Setting Sweden. Participants Older adults (mean age 82.4 ± 7.8) who had a fall risk assessment using the DFRI at baseline (N = 128,596). Measurements Information on all fall‐related injuries, all fall‐related head injuries and hip fractures, and all‐cause mortality was collected from the Swedish Patient Register and Cause of Death Register. The predictive role of DFRI was calculated using Poisson regression models with age, sex, height, weight, and comorbidities as covariates, taking time to outcome or end of study into account. Results During a median follow‐up of 253 days (interquartile range 90–402 days) (>80,000 patient‐years), 15,299 participants had a fall‐related injury, 2,864 a head injury, and 2,557 a hip fracture, and 23,307 died. High fall risk (DFRI ≥3) independently predicted fall‐related injury (hazard ratio (HR) = 1.43, 95% confidence interval (CI) = 1.39–1.49), hip fracture (HR = 1.51, 95% CI =1.38–1.66), head injury (HR = 1.12, 95% CI = 1.03–1.22), and all‐cause mortality (HR = 1.39, 95% CI = 1.35–1.43). DFRI more strongly predicted head injury (HR = 1.29, 95% CI = 1.21–1.36 vs HR = 1.08, 95% CI = 1.04–1.11) and hip fracture (HR = 1.41, 95% CI = 1.30–1.53 vs HR = 1.08, 95% CI = 1.05–1.11) in 70‐year old men than in 90‐year old women (P < .001). Conclusion Fall risk assessment using DFRI independently predicts fall‐related injury, fall‐related head injury and hip fracture, and all‐cause mortality in older men and women, indicating its clinical usefulness to identify individuals who would benefit from interventions

Global impact of COVID-19 on non-communicable disease management: descriptive analysis of access to FRAX fracture risk online tool for prevention of osteoporotic fractures

Summary The COVID-19 pandemic, and its management, is markedly impacting the management of osteoporosis as judged by access to online FRAX fracture risk assessments. Globally, access was 58% lower in April than in February 2020. Strategies to improve osteoporosis care, with greater use of fracture risk assessments, offer a partial solution. Introduction The COVID-19 pandemic is having a significant detrimental impact on the management of chronic diseases including osteoporosis. We have quantified the global impact by examining changes in the usage of online FRAX fracture risk assessments before and after the declaration of the pandemic (11 March 2020). Methods The study comprised a retrospective analysis using GoogleAnalytics data on daily sessions on the FRAX® website (www.sheffield.ac.uk/FRAX) from November 2019 to April 2020 (main analysis period February–April 2020), and the geographical source of that activity. Results Over February–April 2020, the FRAX website recorded 460,495 sessions from 184 countries, with 210,656 sessions in February alone. In March and April, the number of sessions fell by 23.1% and 58.3% respectively, a pattern not observed over the same period in 2019. There were smaller reductions in Asia than elsewhere, partly related to earlier and less-marked nadirs in some countries (China, Taiwan, Hong Kong, South Korea and Vietnam). In Europe, the majority of countries (24/31, 77.4%) reduced usage by at least 50% in April. Seven countries showed smaller reductions (range − 2.85 to − 44.1%) including Poland, Slovakia, Czech Republic, Germany, Norway, Sweden and Finland. There was no significant relationship between the reduction in FRAX usage and measures of disease burden such as COVID-attributed deaths per million of the population. Conclusion This study documents a marked global impact of the COVID-19 pandemic on the management of osteoporosis as reflected by FRAX online fracture risk assessments. The analysis suggests that impact may relate to the societal and healthcare measures taken to ameliorate the pandemic

Optical excitations in organic molecules, clusters and defects studied by first-principles Green's function methods

Spectroscopic and optical properties of nanosystems and point defects are discussed within the framework of Green's function methods. We use an approach based on evaluating the self-energy in the so-called GW approximation and solving the Bethe-Salpeter equation in the space of single-particle transitions. Plasmon-pole models or numerical energy integration, which have been used in most of the previous GW calculations, are not used. Fourier transforms of the dielectric function are also avoided. This approach is applied to benzene, naphthalene, passivated silicon clusters (containing more than one hundred atoms), and the F center in LiCl. In the latter, excitonic effects and the $1s \to 2p$ defect line are identified in the energy-resolved dielectric function. We also compare optical spectra obtained by solving the Bethe-Salpeter equation and by using time-dependent density functional theory in the local, adiabatic approximation. From this comparison, we conclude that both methods give similar predictions for optical excitations in benzene and naphthalene, but they differ in the spectra of small silicon clusters. As cluster size increases, both methods predict very low cross section for photoabsorption in the optical and near ultra-violet ranges. For the larger clusters, the computed cross section shows a slow increase as function of photon frequency. Ionization potentials and electron affinities of molecules and clusters are also calculated.Comment: 9 figures, 5 tables, to appear in Phys. Rev. B, 200

Ability of tropical forest soils of French Guiana and Reunion to depollute woods impregnated with biocides

Our study sought to fine-tune knowledge about those microorganisms, particularly wood-decaying fungi degrading pollutants in situ. With a view to the depollution or bioremediation of treated woods, wood-decaying microorganisms from tropical forest soils in French Guiana and the island of Reunion were assessed for their ability to degrade toxic biocides such as pentachlorophenol (PCP) or copper chromium arsenic compounds (CCA). The degradation of red pine (Pinus resinosa) test pieces was monitored and it was found that the soil from French Guiana was more efficient than the soil from Reunion in terms of microbial activity in relation to these two biocides. A significant difference in weight loss was found for the red pinetest pieces treated with CCA and PCP, varying in a ratio of one to two (18% and 30%, respectively). In addition, a study of wood and soil fungus communities using D-HPLC and CE-SSCP, then analysed by a PCA, showed that biocide products leached into the soil had an impact on the fungus communities, which differed depending on the sampling time and on the wood treatment. Lastly, these results confirmed that CCA was less leachable and less degradable by microorganisms in these soils than PCP. (Résumé d'auteur

A surrogate FRAX model for the Kyrgyz Republic

Summary The hip fracture rates from Kazakhstan were used to create a surrogate FRAX® model for the Kyrgyz Republic. Introduction The International Society for Clinical Densitometry and International Osteoporosis Foundation recommend utilizing a surrogate FRAX model, based on the country-specific risk of death, and fracture data based on a country where fracture rates are considered to be representative of the index country. Objective This paper describes a surrogate FRAX model for the Kyrgyz Republic. Methods The FRAX model used the incidence of hip fracture from the neighbouring country of Kazakhstan and the death risk for the Kyrgyz Republic. Results Compared with the model for Kazakhstan, the surrogate model gave somewhat higher 10-year fracture probabilities for men between 60 and 80 years of age and lower probabilities for men above the age of 80. For women the probabilities were similar up to the age of 75–80 years and then lower. There were very close correlations in fracture probabilities between the surrogate and authentic models (1.00) so that the use of the Kyrgyz model had little impact on the rank order of risk. It was estimated that 2752 hip fractures arose in 2015 in individuals over the age of 50 years in the Kyrgyz Republic, with a predicted increase by 207% to 8435 in 2050. Conclusion The surrogate FRAX model for the Kyrgyz Republic provides the opportunity to determine fracture probability among the Kyrgyz population and help guide decisions about treatment