Factors influencing cranial variation between prehistoric Japanese forager populations.

Understanding the factors shaping human crania has long been a goal of biological anthropology, and climate, diet, and population history are three of the most well-established influences. The effects of these factors are, however, rarely compared within a single, variable population, limiting interpretations of their relative contribution to craniofacial form. Jomon prehistoric foragers inhabited Japan throughout its climatic and ecological range and developed correspondingly varied modes of subsistence. We have previously demonstrated that a large sample of Jomon crania showed no clear climatic pattern; here, we examine variation in Jomon crania in more detail to determine if dietary factors and/or population history influence human intrapopulation variation at this scale. Based on well-established archaeological differences, we divide the Jomon into dietary groups and use geometric morphometric methods to analyse relationships between cranial shape, diet, and population history. We find evidence for diet-related influences on the shape of the neurocranium, particularly in the temporalis region. These shape differences may be interpreted in the context of regional variation in the biomechanical requirements of different diets. More experimental biomechanical and nutritional evidence is needed, however, to move suggested links between dietary content and cranial shape from plausible to well-supported. In contrast with the global scale of human variation, where neutral processes are the strongest influence on cranial shape, we find no pattern of population history amongst individuals from these Jomon sites. The determinants of cranial morphology are complex and the effect of diet is likely mediated by factors including sex, social factors, and chronology. Our results underline the subtlety of the effects of dietary variation beyond the forager/farmer dichotomy on cranial morphology and contribute to our understanding of the complexity of selective pressures shaping human phenotypes on different geographic scales. Supplementary Information: The online version contains supplementary material available at 10.1007/s12520-023-01901-6.

Multiproxy bioarchaeological data reveals interplay between growth, diet and population dynamics across the transition to farming in the central Mediterranean.

The transition to farming brought on a series of important changes in human society, lifestyle, diet and health. The human bioarchaeology of the agricultural transition has received much attention, however, relatively few studies have directly tested the interrelationship between individual lifestyle factors and their implications for understanding life history changes among the first farmers. We investigate the interplay between skeletal growth, diet, physical activity and population size across 30,000 years in the central Mediterranean through a 'big data' cross-analysis of osteological data related to stature (n = 361), body mass (n = 334) and long bone biomechanics (n = 481), carbon (δ13C) and nitrogen (δ15N) stable isotopes (n = 1986 human, n = 475 animal) and radiocarbon dates (n = 5263). We present the observed trends on a continuous timescale in order to avoid grouping our data into assigned 'time periods', thus achieving greater resolution and chronological control over our analysis. The results identify important changes in human life history strategies associated with the first farmers, but also highlight the long-term nature of these trends in the millennia either side of the agricultural transition. The integration of these different data is an important step towards disentangling the complex relationship between demography, diet and health, and reconstruct life history changes within a southern European context. We believe the methodological approach adopted here has broader global implications for bioarchaeological studies of human adaptation more generally.

Patient empowerment improves follow-up data collection after fetal surgery for spina bifida: institutional audit.

OBJECTIVES: To define and grade fetal and maternal adverse events following fetal surgery for spina bifida and to report on the impact of engaging patients in collecting follow-up data. METHODS: This prospective single-center audit included 100 consecutive patients undergoing fetal surgery for spina bifida between January 2012 and December 2021. In our setting, patients return to their referring unit for further pregnancy care and delivery. On discharge, referring hospitals were requested to return outcome data. For this audit, we prompted patients and referring hospitals to provide data in cases of missing outcomes. Outcomes were categorized as missing, returned spontaneously or returned following additional request, by the patient and/or referring center. Postoperative maternal and fetal complications until delivery were defined and graded according to Maternal and Fetal Adverse Event Terminology (MFAET) and the Clavien-Dindo classification. RESULTS: There were no maternal deaths, but severe maternal complications occurred in seven women (anemia in pregnancy, postpartum hemorrhage, pulmonary edema, lung atelectasis, urinary tract obstruction and placental abruption). No cases of uterine rupture were reported. Perinatal death occurred in 3% of fetuses and other severe fetal complications in 15% (perioperative fetal bradycardia/cardiac dysfunction, fistula-related oligohydramnios, chorioamnionitis and preterm prelabor rupture of membranes (PPROM) before 32 weeks). PPROM occurred in 42% of patients and, overall, delivery took place at a median gestational age of 35.3 weeks (interquartile range, 34.0-36.6 weeks). Information provided following additional request, from both centers and patients but mainly from the latter, reduced missing data by 21% for gestational age at delivery, 56% for uterine-scar status at birth and 67% for shunt insertion at 12 months. Compared with the generic Clavien-Dindo classification, the MFAET system ranked complications in a more clinically relevant way. CONCLUSIONS: The nature and rate of severe complications following fetal surgery for spina bifida were similar to those reported in other large series. Spontaneous return of outcome data by referring centers was low, yet patient empowerment improved data collection. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

[Artificial neural networks as a psychiatric instrument]. / Artificiële neurale netwerken als psychiatrisch instrument.

BACKGROUND: Artificial intelligence (AI) has evolved enormously over the past decade and is increasingly being applied to a range of domains, including psychiatry. AI encompasses several modalities, including artificial neural networks (ANNs), referring to computer models partly based on the workings of the brain. ANNs have existed since the ’50s, but only became ‘mainstream’ since the 2010s. The fact that they are inspired by the workings of the brain raises the question of whether they can also be used to model the (dys)functioning of the brain. This question led to the advent of the research field ‘computational psychiatry’. AIM: This article aims at providing an accessible introduction to artificial neural networks, and potential applications hereof in contemporary psychiatric practice. METHOD: Literature review with some examples. RESULTS: In this article we try to outline with some concrete examples what artificial neural networks are and how they can be used to model mechanisms in the brain. We successively discuss ANNs as a model of the human visual system, as a model of prosopagnosia and as a model of auditory hallucinations and finally as a model of autism spectrum disorder. We also describe a number of limitations of this approach. CONCLUSION: A computer model that models the entire brain is challenging at present, but current models can help in testing hypotheses concerning possible mechanisms that give rise to a wide range of neuropsychiatric conditions.

A longitudinal study of the association between basal ganglia volumes and psychomotor symptoms in subjects with late life depression undergoing ECT.

Psychomotor dysfunction (PMD) is a core element and key contributor to disability in late life depression (LLD), which responds well to electroconvulsive therapy (ECT). The neurobiology of PMD and its response to ECT are not well understood. We hypothesized that PMD in LLD is associated with lower striatal volume, and that striatal volume increase following ECT explains PMD improvement. We analyzed data from a two-center prospective cohort study of 110 LLD subjects (>55 years) receiving ECT. Brain MRI and assessment of mood, cognition, and PMD was performed 1 week before, 1 week after, and 6 months after ECT. Volumetry of the caudate nucleus, putamen, globus pallidus, and nucleus accumbens was derived from automatically segmented brain MRIs using Freesurfer®. Linear multiple regression analyses were used to study associations between basal ganglia volume and PMD. Brain MRI was available for 66 patients 1 week post ECT and in 22 patients also six months post ECT. Baseline PMD was associated with a smaller left caudate nucleus. One week after ECT, PMD improved and volume increases were detected bilaterally in the caudate nucleus and putamen, and in the right nucleus accumbens. Improved PMD after ECT did not relate to the significant volume increases in these structures, but was predicted by a nonsignificant volume change in the right globus pallidus. No volume differences were detected 6 months after ECT, compared to baseline. Although PMD is related to lower striatal volume in LLD, ECT-induced increase of striatal volume does not explain PMD improvement.

Implementing a genomic rotational crossbreeding scheme to promote local dairy cattle breeds-A simulation study.

In dairy cattle breeding, there is a clear trend toward the use of only a few high-yielding breeds. One main reason is that efficient breeding programs require a certain population size. Since some numerically small breeds are well known for their functional traits, they might be an interesting crossing partner for high-yielding breeds with the aim to utilize heterosis. This simulation study investigated the transition period of a small cattle population for the implementation of genomic selection and rotational crossbreeding with a high-yielding breed. Real SNP chip genotype data from the numerically small red dairy breed Angler and the high-yielding breed Holstein Friesian were used to simulate the base generations, from which rotational crossbreeding was conducted for 10 generations. A polygenic trait with many quantitative trait loci with additive and directional dominance effects was simulated. Different selection methods for Angler sires (purebred performance, crossbred performance, and weighted purebred-crossbred performance) and different sizes and structures of the reference population (Angler, crossbred animals, and Angler plus crossbred animals) were considered. The results showed that the implementation of a genomic rotational crossbreeding scheme is an appealing option to promote the numerically small Angler breed. The growing reference population consisting of Angler and crossbred individuals maximized the genetic gain for Angler and the performance level for the crossbred individuals. Selection for purebred performance, crossbred performance, or a weighted combination of both hardly affected the results, and differences between selection scenarios were observed only in the long term with decreasing purebred-crossbred correlations.

Synchronized beamline at FLASH2 based on high-order harmonic generation for two-color dynamics studies.

We present the design, integration, and operation of the novel vacuum ultraviolet (VUV) beamline installed at the free-electron laser (FEL) FLASH. The VUV source is based on high-order harmonic generation (HHG) in gas and is driven by an optical laser system synchronized with the timing structure of the FEL. Ultrashort pulses in the spectral range from 10 to 40 eV are coupled with the FEL in the beamline FL26, which features a reaction microscope (REMI) permanent endstation for time-resolved studies of ultrafast dynamics in atomic and molecular targets. The connection of the high-pressure gas HHG source to the ultra-high vacuum FEL beamline requires a compact and reliable system, able to encounter the challenging vacuum requirements and coupling conditions. First commissioning results show the successful operation of the beamline, reaching a VUV focused beam size of about 20 µm at the REMI endstation. Proof-of-principle photo-electron momentum measurements in argon indicate the source capabilities for future two-color pump-probe experiments.

Evidence of different climatic adaptation strategies in humans and non-human primates.

To understand human evolution it is critical to clarify which adaptations enabled our colonisation of novel ecological niches. For any species climate is a fundamental source of environmental stress during range expansion. Mammalian climatic adaptations include changes in size and shape reflected in skeletal dimensions and humans fit general primate ecogeographic patterns. It remains unclear however, whether there are also comparable amounts of adaptation in humans, which has implications for understanding the relative importance of biological/behavioural mechanisms in human evolution. We compare cranial variation between prehistoric human populations from throughout Japan and ecologically comparable groups of macaques. We compare amounts of intraspecific variation and covariation between cranial shape and ecological variables. Given equal rates and sufficient time for adaptation for both groups, human conservation of non-human primate adaptation should result in comparable variation and patterns of covariation in both species. In fact, we find similar amounts of intraspecific variation in both species, but no covariation between shape and climate in humans, contrasting with strong covariation in macaques. The lack of covariation in humans may suggest a disconnect in climatic adaptation strategies from other primates. We suggest this is due to the importance of human behavioural adaptations, which act as a buffer from climatic stress and were likely key to our evolutionary success.

Assessing the accuracy of body mass estimation equations from pelvic and femoral variables among modern British women of known mass.

Femoral head diameter is commonly used to estimate body mass from the skeleton. The three most frequently employed methods, designed by Ruff, Grine, and McHenry, were developed using different populations to address different research questions. They were not specifically designed for application to female remains, and their accuracy for this purpose has rarely been assessed or compared in living populations. This study analyzes the accuracy of these methods using a sample of modern British women through the use of pelvic CT scans (n = 97) and corresponding information about the individuals' known height and weight. Results showed that all methods provided reasonably accurate body mass estimates (average percent prediction errors under 20%) for the normal weight and overweight subsamples, but were inaccurate for the obese and underweight subsamples (average percent prediction errors over 20%). When women of all body mass categories were combined, the methods provided reasonable estimates (average percent prediction errors between 16 and 18%). The results demonstrate that different methods provide more accurate results within specific body mass index (BMI) ranges. The McHenry Equation provided the most accurate estimation for women of small body size, while the original Ruff Equation is most likely to be accurate if the individual was obese or severely obese. The refined Ruff Equation was the most accurate predictor of body mass on average for the entire sample, indicating that it should be utilized when there is no knowledge of the individual's body size or if the individual is assumed to be of a normal body size. The study also revealed a correlation between pubis length and body mass, and an equation for body mass estimation using pubis length was accurate in a dummy sample, suggesting that pubis length can also be used to acquire reliable body mass estimates. This has implications for how we interpret body mass in fossil hominins and has particular relevance to the interpretation of the long pubic ramus that is characteristic of Neandertals.

Evolution of Earth-like Extrasolar Planetary Atmospheres: Assessing the Atmospheres and Biospheres of Early Earth Analog Planets with a Coupled Atmosphere Biogeochemical Model.

Understanding the evolution of Earth and potentially habitable Earth-like worlds is essential to fathom our origin in the Universe. The search for Earth-like planets in the habitable zone and investigation of their atmospheres with climate and photochemical models is a central focus in exoplanetary science. Taking the evolution of Earth as a reference for Earth-like planets, a central scientific goal is to understand what the interactions were between atmosphere, geology, and biology on early Earth. The Great Oxidation Event in Earth's history was certainly caused by their interplay, but the origin and controlling processes of this occurrence are not well understood, the study of which will require interdisciplinary, coupled models. In this work, we present results from our newly developed Coupled Atmosphere Biogeochemistry model in which atmospheric O2 concentrations are fixed to values inferred by geological evidence. Applying a unique tool (Pathway Analysis Program), ours is the first quantitative analysis of catalytic cycles that governed O2 in early Earth's atmosphere near the Great Oxidation Event. Complicated oxidation pathways play a key role in destroying O2, whereas in the upper atmosphere, most O2 is formed abiotically via CO2 photolysis. The O2 bistability found by Goldblatt et al. ( 2006 ) is not observed in our calculations likely due to our detailed CH4 oxidation scheme. We calculate increased CH4 with increasing O2 during the Great Oxidation Event. For a given atmospheric surface flux, different atmospheric states are possible; however, the net primary productivity of the biosphere that produces O2 is unique. Mixing, CH4 fluxes, ocean solubility, and mantle/crust properties strongly affect net primary productivity and surface O2 fluxes. Regarding exoplanets, different "states" of O2 could exist for similar biomass output. Strong geological activity could lead to false negatives for life (since our analysis suggests that reducing gases remove O2 that masks its biosphere over a wide range of conditions). Key Words: Early Earth-Proterozoic-Archean-Oxygen-Atmosphere-Biogeochemistry-Photochemistry-Biosignatures-Earth-like planets. Astrobiology 16, 27-54.

A simple method for cryopreservation of shoot tips of Arabidopsis genotypes.

　　BACKGROUND: The use of the model plant Arabidopsis could be a valuable tool to elucidate the basic mechanisms involved in plant cryopreservation. OBJECTIVE: A simple and powerful protocol, independent of Arabidopsis genotypes, was established using a PVS2 protocol. MATERIALS AND METHODS: Two PVS2 (a and b), one PVS3 droplet-vitrification and one DMSO droplet-freezing protocol were tested with alternating temperatures during the growing phase of donor plants. RESULTS: PVS2 protocols, including cold acclimation of donor plants, resulted in highest recovery. The PVS2a protocol was successfully applied to a collection of different Arabidopsis genotypes with an average recovery of 94%. In addition, Differential Scanning Calorimetry confirmed the occurrence of glass transitions in the PVS3 and PVS2 protocols. CONCLUSION: The PVS2a protocol is suitable to screen the large collection of Arabidopsis mutants and transgenic lines with the aim to identify cellular functions associated with cryopreservation tolerance.

Ancient Ethiopian genome reveals extensive Eurasian admixture throughout the African continent.

Characterizing genetic diversity in Africa is a crucial step for most analyses reconstructing the evolutionary history of anatomically modern humans. However, historic migrations from Eurasia into Africa have affected many contemporary populations, confounding inferences. Here, we present a 12.5× coverage ancient genome of an Ethiopian male ("Mota") who lived approximately 4500 years ago. We use this genome to demonstrate that the Eurasian backflow into Africa came from a population closely related to Early Neolithic farmers, who had colonized Europe 4000 years earlier. The extent of this backflow was much greater than previously reported, reaching all the way to Central, West, and Southern Africa, affecting even populations such as Yoruba and Mbuti, previously thought to be relatively unadmixed, who harbor 6 to 7% Eurasian ancestry.

Incidence of bleeding in 8172 percutaneous ultrasound-guided intraabdominal diagnostic and therapeutic interventions - results of the prospective multicenter DEGUM interventional ultrasound study (PIUS study).

PURPOSE: To analyse the incidence of bleeding after percutaneous ultrasound guided diagnostic and therapeutic intraabdominal interventions in a prospective multicentre study (DEGUM percutaneous interventional ultrasound study). MATERIALS AND METHODS: Within a time period of 2 years diagnostic and therapeutic intraabdominal interventions (with the exclusion of ascites paracentesis) performed percutaneously under continuous ultrasound (US) guidance were prospectively assessed using a pseudonymized standardized web site entry form. Number and type of intervention, operator experience, patient characteristics, medication, lab data as well as technical aspects of the procedure and bleeding complications were analysed according to the interventional radiology standards. RESULTS: 8172 US-guided intraabdominal interventions (liver n = 5903; pancreas n = 501, kidney n = 434, lymph node = 272, biliary system n = 153, spleen n = 63, other abdominal organs and extra-organic targets n = 999) were analysed in 30 hospitals. The majority were diagnostic biopsies including 1780 liver parenchyma, 3400 focal liver lesions and 404 pancreatic lesions. 7525 interventions (92.1 %) were performed in hospitalized patients (mean age 62.6 years). Most operators were highly experienced in US-guided interventions (> 500 interventions prior to the study n = 5729; 70.1 %). Sedation was administered in 1131 patients (13.8 %). Needle diameter was ≥ 1 mm in 7162 punctures (87.9 %) with main focus on core needle biopsies (18 G, n = 4185). Clinically relevant bleeding complications with need of transfusion (0.4 %), surgical bleeding control (0.1 %) and radiological coiling (0.05 %) were very rare. Bleeding complications with fatal outcome occurred in four patients (0.05 %). The frequency of major bleeding complications was significantly higher in patients with an INR > 1.5 (p < 0.001) and patients taking a medication potentially interfering with platelet function or plasmatic coagulation (p < 0.0333). CONCLUSION: This prospective multicentre study confirms the broad spectrum of percutaneous US-guided intraabdominal interventions. However diagnostic liver biopsies dominate with the use of core needle biopsies (18 G). Percutaneous US-guided interventions performed by experienced sonographers are associated with a low bleeding risk. Major bleeding complications are very rare. A pre-interventional INR < 1.5 and individual medication risk assessment are recommended.

Anti-inflammatory and anti-bacterial properties of tetramethylhexadecenyl succinyl cysteine (TSC): a skin-protecting cosmetic functional ingredient.

BACKGROUND: The skin is the first line of defence against exposure to microbial, physical, environmental and chemical insults. In mobilizing a protective response, several different cell types located in our skin release and respond to pro-inflammatory cytokines ensuring skin homeostasis and health. However, chronic activation of this response eventually causes damage resulting in premature ageing. Diosodium tetramethylhexadecenyl succinyl cysteine (TSC or SIG1273), an isoprenylcysteine small molecule, down modulates these inflammatory signalling pathways in various cell types (keratinocytes, peripheral blood mononuclear cells (PBMCs) and endothelial cells) and possesses anti-bacterial properties. Thus, TSC represents a novel cosmetic functional ingredient that provides a broad spectrum of benefits for the skin. OBJECTIVE: To assess the anti-inflammatory properties of TSC in several cutaneous cell types and further investigate its anti-microbial activity. METHODS: Cultured normal human epidermal keratinocytes were exposed to chemical irritant phorbol 12-myrisate 13-acetate (TPA) or ultraviolet-B light (UVB) to induce pro-inflammatory cytokine (IL-6, IL-8 and TNF-α) production. T-cell receptor (TCR) activation of PBMCs and nickel (Ni(2+) ) treatments of human dermal microvascular endothelial cells (HDMECs) were performed resulting in IL-4, IL-6, IL-8 and IL-17 production. Streptococcus pyogenes were cultured to determine minimal inhibitory concentration values. RESULTS: In vitro studies demonstrate TSC blocks TPA and UVB-induced cytokine production in cultured keratinocytes. Similarly, TSC inhibits overproduction of IL-4 and IL-17 in T-cell receptor (TCR)-activated PBMCs as well as nickel induction of IL-6 and IL-8 in HDMECs. Lastly, TSC demonstrated anti-microbial properties, inhibiting cell growth of S. pyogenes. CONCLUSIONS: Tetramethylhexadecenyl succinyl cysteine represents a novel cosmetic functional ingredient that provides a dual modulating benefit of skin protection to individuals by reducing inflammation in keratinocytes, endothelial and mononuclear cell types and S. pyogenes counts.

Potential biosignatures in super-Earth atmospheres II. Photochemical responses.

Spectral characterization of super-Earth atmospheres for planets orbiting in the habitable zone of M dwarf stars is a key focus in exoplanet science. A central challenge is to understand and predict the expected spectral signals of atmospheric biosignatures (species associated with life). Our work applies a global-mean radiative-convective-photochemical column model assuming a planet with an Earth-like biomass and planetary development. We investigated planets with gravities of 1g and 3g and a surface pressure of 1 bar around central stars with spectral classes from M0 to M7. The spectral signals of the calculated planetary scenarios have been presented by in an earlier work by Rauer and colleagues. The main motivation of the present work is to perform a deeper analysis of the chemical processes in the planetary atmospheres. We apply a diagnostic tool, the Pathway Analysis Program, to shed light on the photochemical pathways that form and destroy biosignature species. Ozone is a potential biosignature for complex life. An important result of our analysis is a shift in the ozone photochemistry from mainly Chapman production (which dominates in Earth's stratosphere) to smog-dominated ozone production for planets in the habitable zone of cooler (M5-M7)-class dwarf stars. This result is associated with a lower energy flux in the UVB wavelength range from the central star, hence slower planetary atmospheric photolysis of molecular oxygen, which slows the Chapman ozone production. This is important for future atmospheric characterization missions because it provides an indication of different chemical environments that can lead to very different responses of ozone, for example, cosmic rays. Nitrous oxide, a biosignature for simple bacterial life, is favored for low stratospheric UV conditions, that is, on planets orbiting cooler stars. Transport of this species from its surface source to the stratosphere where it is destroyed can also be a key process. Comparing 1g with 3g scenarios, our analysis suggests it is important to include the effects of interactive chemistry.

Earthquake in a maze: compressional rupture branching during the 2012 M(w) 8.6 Sumatra earthquake.

Seismological observations of the 2012 moment magnitude 8.6 Sumatra earthquake reveal unprecedented complexity of dynamic rupture. The surprisingly large magnitude results from the combination of deep extent, high stress drop, and rupture of multiple faults. Back-projection source imaging indicates that the rupture occurred on distinct planes in an orthogonal conjugate fault system, with relatively slow rupture speed. The east-southeast-west-northwest ruptures add a new dimension to the seismotectonics of the Wharton Basin, which was previously thought to be controlled by north-south strike-slip faulting. The rupture turned twice into the compressive quadrant, against the preferred branching direction predicted by dynamic Coulomb stress calculations. Orthogonal faulting and compressional branching indicate that rupture was controlled by a pressure-insensitive strength of the deep oceanic lithosphere.

Arzoxifene versus raloxifene: effect on bone and safety parameters in postmenopausal women with osteoporosis.

UNLABELLED: Arzoxifene increased bone mineral density and decreased bone turnover to a significantly greater extent than raloxifene. The hot flush incidence was lower with arzoxifene than raloxifene. INTRODUCTION: To assess the effect of arzoxifene versus raloxifene on change in lumbar spine (LS) bone mineral density (BMD) in postmenopausal women with osteoporosis. METHODS: In this 12-month study (NEXT trial), participants were randomly assigned to arzoxifene 20 mg/day (N = 158) or raloxifene 60 mg/day (N = 162). All received daily calcium and vitamin D. Change in LS BMD was assessed by DXA. Secondary objectives included assessment of femoral neck (FN) and total hip BMD, serum bone turnover markers, and safety. RESULTS: Treatment groups were similar at baseline (mean age 63 years, mean LS BMD T-score -2.9). At 12 months, the increase in LS BMD with arzoxifene was greater than with raloxifene (+2.75% vs. +1.66%), as was FN and total hip BMD (P < 0.05). For LS and FN, this effect was also evident at 6 months. Arzoxifene reduced bone turnover to a greater extent than raloxifene at 3, 6, and 12 months (P < 0.05). The proportion of women reporting ≥ 1 adverse event did not differ between treatment groups, nor did vaginal bleeding. No cases of endometrial polyps, hyperplasia, or cancer were reported. Nasopharyngitis and bronchitis were reported more frequently with arzoxifene versus raloxifene (10.1% vs. 2.5%, and 5.1% vs. 0%, respectively) and new/worsening hot flushes were reported less frequently with arzoxifene (7.0% vs. 16.7%) (P < 0.05). CONCLUSIONS: Arzoxifene increased BMD and suppressed bone turnover to a greater extent than raloxifene and resulted in a lower incidence of new/worsening hot flushes. Based on subsequent findings from a fracture outcome study, this difference did not translate into improved fracture efficacy.

The effect of teriparatide compared with risedronate on reduction of back pain in postmenopausal women with osteoporotic vertebral fractures.

UNLABELLED: The effect of teriparatide and risedronate on back pain was tested, and there was no difference in the proportion of patients experiencing a reduction in back pain between groups after 6 or 18 months. Patients receiving teriparatide had greater increases in bone mineral density and had fewer vertebral fractures. INTRODUCTION: This study aimed to understand the effect of teriparatide in reducing back pain in patients with prevalent back pain and vertebral fracture compared to risedronate. METHODS: In an 18-month randomized, double-blind, double-dummy trial, we investigated the effects of teriparatide (20 µg/day) vs. risedronate (35 mg/week) in postmenopausal women with back pain likely due to vertebral fracture. The primary objective was to compare the proportion of subjects reporting ≥30% reduction in worst back pain severity from baseline to 6 months as assessed by a numeric rating scale in each treatment group. Pre-specified secondary and exploratory outcomes included assessments of average and worst back pain at additional time points, disability and quality of life, bone mineral density, incidence of fractures, and safety. RESULTS: At 6 months, 59% of teriparatide and 57% of risedronate patients reported ≥30% reduction in worst back pain and there were no differences between groups in the proportion of patients experiencing reduction in worst or average back pain at any time point, disability, or quality of life. There was a greater increase from baseline in bone mineral density at the lumbar spine (p = 0.001) and femoral neck (p = 0.02) with teriparatide compared to risedronate and a lower incidence of vertebral fractures at 18 months (4% teriparatide and 9% risedronate; p = 0.01). Vertebral fractures were less severe (p = 0.04) in the teriparatide group. There was no difference in the overall incidence of adverse events. CONCLUSIONS: Although there were no differences in back pain-related endpoints, patients receiving teriparatide had greater skeletal benefit than those receiving risedronate.