Organization of the human cerebral cortex estimated within individuals: networks, global topography, and function.

The cerebral cortex is populated by specialized regions that are organized into networks. Here we estimated networks from functional MRI (fMRI) data in intensively sampled participants. The procedure was developed in two participants (scanned 31 times) and then prospectively applied to 15 participants (scanned 8-11 times). Analysis of the networks revealed a global organization. Locally organized first-order sensory and motor networks were surrounded by spatially adjacent second-order networks that linked to distant regions. Third-order networks possessed regions distributed widely throughout association cortex. Regions of distinct third-order networks displayed side-by-side juxtapositions with a pattern that repeated across multiple cortical zones. We refer to these as supra-areal association megaclusters (SAAMs). Within each SAAM, two candidate control regions were adjacent to three separate domain-specialized regions. Response properties were explored with task data. The somatomotor and visual networks responded to body movements and visual stimulation, respectively. Second-order networks responded to transients in an oddball detection task, consistent with a role in orienting to salient events. The third-order networks, including distinct regions within each SAAM, showed two levels of functional specialization. Regions linked to candidate control networks responded to working memory load across multiple stimulus domains. The remaining regions dissociated across language, social, and spatial/episodic processing domains. These results suggest that progressively higher-order networks nest outward from primary sensory and motor cortices. Within the apex zones of association cortex, there is specialization that repeatedly divides domain-flexible from domain-specialized regions. We discuss implications of these findings, including how repeating organizational motifs may emerge during development.NEW & NOTEWORTHY The organization of cerebral networks was estimated within individuals with intensive, repeat sampling of fMRI data. A hierarchical organization emerged in each individual that delineated first-, second-, and third-order cortical networks. Regions of distinct third-order association networks consistently exhibited side-by-side juxtapositions that repeated across multiple cortical zones, with clear and robust functional specialization among the embedded regions.

Development and Optimization of the Veterans Affairs' National Heart Failure Dashboard for Population Health Management.

BACKGROUND: In 2020, the Veterans Affairs (VA) health care system deployed a heart failure (HF) dashboard for use nationally. The initial version was notably imprecise and unreliable for the identification of HF subtypes. We describe the development and subsequent optimization of the VA national HF dashboard. MATERIALS AND METHODS: This study describes the stepwise process for improving the accuracy of the VA national HF dashboard, including defining the initial dashboard, improving case definitions, using natural language processing for patient identification, and incorporating an imaging-quality hierarchy model. Optimization further included evaluating whether to require concurrent ICD-codes for inclusion in the dashboard and assessing various imaging modalities for patient characterization. RESULTS: Through multiple rounds of optimization, the dashboard accuracy (defined as the proportion of true results to the total population) was improved from 54.1% to 89.2% for the identification of HF with reduced ejection fraction (HFrEF) and from 53.9% to 88.0% for the identification of HF with preserved ejection fraction (HFpEF). To align with current guidelines, HF with mildly reduced ejection fraction (HFmrEF) was added to the dashboard output with 88.0% accuracy. CONCLUSIONS: The inclusion of an imaging-quality hierarchy model and natural-language processing algorithm improved the accuracy of the VA national HF dashboard. The revised dashboard informatics algorithm has higher use rates and improved reliability for the health management of the population.

The impact of digital technology use on nurses' professional identity and relations of power: a literature review.

AIM: This study seeks to review how the use of digital technologies in clinical nursing affects nurses' professional identity and the relations of power within clinical environments. DESIGN: Literature review. DATA SOURCES: PubMed and CINAHL databases were searched in April 2023. METHODS: We screened 874 studies in English and German, of which 15 were included in our final synthesis reflecting the scientific discourse from 1992 until 2023. RESULTS: Our review revealed relevant effects of digital technologies on nurses' professional identity and power relations. Few studies cover outcomes relating to identity, such as moral agency or nurses' autonomy. Most studies describe negative impacts of technology on professional identity, for example, creating a barrier between nurses and patients leading to decreased empathetic interaction. Regarding power relations, technologically skilled nurses can yield power over colleagues and patients, while depending on technology. The investigation of these effects is underrepresented. CONCLUSION: Our review presents insights into the relation between technology and nurses' professional identity and prevalent power relations. For future studies, dedicated and critical investigations of digital technologies' impact on the formation of professional identity in nursing are required. IMPLICATIONS FOR THE PROFESSION: Nurses' professional identity may be altered by digital technologies used in clinical care. Nurses, who are aware of the potential effects of digitized work environments, can reflect on the relationship of technology and the nursing profession. IMPACT: The use of digital technology might lead to a decrease in nurses' moral agency and competence to shape patient-centred care. Digital technologies seem to become an essential measure for nurses to wield power over patients and colleagues, whilst being a control mechanism. Our work encourages nurses to actively shape digital care. REPORTING METHOD: We adhere to the JBI Manual for Evidence Synthesis where applicable. EQUATOR reporting guidelines were not applicable for this type of review. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution.

vSEMERA: pilot project assessing health profession students' experiences in an international virtual research program.

BACKGROUND: The "Virtual Semester for Medical Research Aachen" (vSEMERA) is an international, interdisciplinary, virtual education program developed for health profession students. The first edition (2021) was hosted by the Medical Faculty of RWTH Aachen University (Germany) in cooperation with Centro Universitário Christus (Brazil) and Universidad Peruana Cayetano Heredia (Peru). The primary aim of the 12-weeks program was to provide students with skills in health science research and prepare them for scientific career paths. METHODS: vSEMERA was built on a virtual learning platform, the "vSEMERA-Campus", designed to foster students' learning process and social interactions. Maximum flexibility was offered through synchronous and asynchronous teaching, enabling participants to join via any device from any part of the Globe alongside their regular studies. For the program's first edition (September - November 2021), health profession students from Germany, Brazil, Peru, Spain, and Italy filled all 30 available spots. Satisfaction, quality of the program and courses offered, as well as perceived learning outcomes, were examined using questionnaires throughout and at the end of the program. RESULTS: The program received a rating of 4.38 out of 5 stars. While it met most expectations (4.29 out of 5), participants were unable to attend as many courses as intended (2.81 out of 5), mainly due to scheduling conflicts with the home university schedule (46%), internships (23%), and general timing issues (31%). Participants acknowledged considerable improvements in their scientific skills, English language skills, confidence in scientific project management, research career progression, and enthusiasm for a scientific career. CONCLUSIONS: vSEMERA represents a promising example of an online international learning and exchange program using pedagogical and technological elements of virtual collaboration and teaching. In addition to advancing future vSEMERA editions, our results may offer insights for similar projects that address the targeted integration of scientific research education into an international, digital learning environment.

[From Nazi to Hitler Analyst: The Autobiographical Reinterpretations of the Psychiatrist Johann Recktenwald (1882-1964)]. / Vom Nationalsozialisten zum Hitler-Erklärer: Die autobiografischen Umdeutungen des Psychiaters Johann Recktenwald (1882­1964).

AIM OF THE STUDY: The focus of this article is the psychiatrist Johann Recktenwald (1882-1964) who has so far received little attention: acquitted of the charge of "crimes against humanity", he went public in post-war Germany with a neuropsychiatric treatise on Hitler. But is this appearance as a Hitler-critical psychiatrist consistent with the available historical sources? What was Recktenwald's relationship with the Nazi regime, and how did he behave in the "Third Reich" towards the patients entrusted to his care? METHODS: The paper is largely based on documents from various archives, some of which have been evaluated for the first time, and on court records. The latter are supplemented and compared with the writings of Recktenwald and the available secondary literature. RESULTS: During the "Third Reich", Recktenwald served the Nazi regime in many ways, was jointly responsible for numerous patient murders and thus moved into the role of a Nazi perpetrator. After his acquittal in post-war Germany, he endeavored to construct a personal distance to National Socialism by critically examining Hitler's psychopathology, which at the same time served his own exculpation. CONCLUSION: Recktenwald is a particularly impressive example of the efforts of Nazi perpetrators to retrospectively rewrite their own role in the "Third Reich" - and at the same time a reflection of a post-war society that was willing to accept such biographical reinterpretations in order to avoid coming to terms with the Nazi past.

Vertebral Fractures: Which Radiological Criteria Are Better Associated With the Clinical Course of Osteoporosis?

STUDY PURPOSE: Morphometric methods categorize potential osteoporotic vertebral fractures (OVF) on the basis of loss of vertebral height. A particular example is the widely used semiquantitative morphometric tool proposed by Genant (GSQ). A newer morphologic algorithm-based qualitative (mABQ) tool focuses on vertebral end-plate damage in recognizing OVF. We used data from both sexes in the Canadian Multicentre Osteoporosis Study (CaMos) to compare the 2 methods in identifying OVF at baseline and during 10 years of follow-up. MATERIALS AND METHODS: We obtained lateral thoracic and lumbar spinal radiographs (T4-L4) 3 times, at 5-year intervals, in 828 participants of the population-based CaMos. Logistic regressions were used to study the association of 10-year changes in bone mineral density (BMD) with incident fractures. RESULTS: At baseline, 161 participants had grade 1 and 32 had grade 2 GSQ OVF; over the next 10 years, only 9 of these participants had sustained incident GSQ OVF. Contrastingly, 21 participants at baseline had grade 1 and 48 grade 2 mABQ events; over the next 10 years, 79 subjects experienced incident grade 1 or grade 2 mABQ events. Thus, incident grades 1 and 2 morphologic fractures were 8 times more common than morphometric deformities alone. Each 10-year decrease of 0.01 g/cm2 in total hip BMD was associated with a 4.1% (95% CI: 0.7-7.3) higher odds of having an incident vertebral fracture. CONCLUSIONS: This analysis further suggests that morphometric deformities and morphologic fractures constitute distinct entities; morphologic fractures conform more closely to the expected epidemiology of OVF.

Correction to: Review of Transthyretin Silencers, Stabilizers, and Fibril Removal Agents in the Treatment of Transthyretin Cardiac Amyloid.

On page 2 of the original publication, in the section on TTR Silencers dosing of patisiran in the APOLLO study was stated as being given every 3 months; this is inaccurate as patisiran was dosed every 3 weeks in the APOLLO study.

Review of Transthyretin Silencers, Stabilizers, and Fibril Removal Agents in the Treatment of Transthyretin Cardiac Amyloid.

PURPOSE OF REVIEW: To provide a functional review for practicing clinicians on the current and emerging treatment considerations for transthyretin (TTR) cardiac amyloidosis (ATTR-CA). RECENT FINDINGS: Current treatment considerations are characterized as those silencing TTR translation, stabilizing TTR tetramers, and disrupting amyloid fibril deposition. Historically considered a rare disease state, ATTR-CA is increasingly recognized as an important mediator of heart failure morbidity and mortality. The emergence of widely available therapies for ATTR-CA has developed hope for patients where little was previously present. Thus, it is important that all cardiology clinicians have a functional understanding of the disease state and treatment options. This review will discuss agents within each of the above classes with expanded discussion on tafamidis given its favorable efficacy, safety, and availability. ATTR-CA diagnostic considerations are reviewed with regard to the identification of potential tafamidis candidates, and practical economic considerations are also reviewed.

Tpbpa-Cre-mediated deletion of TFAP2C leads to deregulation of Cdkn1a, Akt1 and the ERK pathway, causing placental growth arrest.

Loss of TFAP2C in mouse leads to developmental defects in the extra-embryonic compartment with lethality at embryonic day (E)7.5. To investigate the requirement of TFAP2C in later placental development, deletion of TFAP2C was induced throughout extra-embryonic ectoderm at E6.5, leading to severe placental abnormalities caused by reduced trophoblast population and resulting in embryonic retardation by E8.5. Deletion of TFAP2C in TPBPA(+) progenitors at E8.5 results in growth arrest of the junctional zone. TFAP2C regulates its target genes Cdkn1a (previously p21) and Dusp6, which are involved in repression of MAPK signaling. Loss of TFAP2C reduces activation of ERK1/2 in the placenta. Downregulation of Akt1 and reduced activation of phosphorylated AKT in the mutant placenta are accompanied by impaired glycogen synthesis. Loss of TFAP2C led to upregulation of imprinted gene H19 and downregulation of Slc38a4 and Ascl2. The placental insufficiency post E16.5 causes fetal growth restriction, with 19% lighter mutant pups. Knockdown of TFAP2C in human trophoblast choriocarcinoma JAr cells inhibited MAPK and AKT signaling. Thus, we present a model where TFAP2C in trophoblasts controls proliferation by repressing Cdkn1a and activating the MAPK pathway, further supporting differentiation of glycogen cells by activating the AKT pathway.

Placental-Specific Overexpression of sFlt-1 Alters Trophoblast Differentiation and Nutrient Transporter Expression in an IUGR Mouse Model.

Since it is known that placental overexpression of the human anti-angiogenic molecule sFlt-1, the main candidate in the progression of preeclampsia, lead to intrauterine growth restriction (IUGR) in mice by lentiviral transduction of mouse blastocysts, we hypothesize that sFlt-1 influence placental morphology and physiology resulting in fetal IUGR. We therefore examined the effect of sFlt-1 on placental morphology and physiology at embryonic day 18.5 with histologic and morphometric analyses, transcript analyses, immunoblotting, and methylation studies. Interestingly, placental overexpression of sFlt-1 leads to IUGR in the fetus and results in lower placental weights. Moreover, we observed altered trophoblast differentiation with reduced expression of IGF2, resulting in a smaller placenta, a smaller labyrinth, and the loss of glycogen cells in the junctional zone. Changes in IGF2 are accompanied by small changes in its DNA methylation, whereas overall DNA methylation is unaffected. In addition, the expression of placental nutrient transporters, such as the glucose diffusion channel Cx26, is decreased. In contrast, the expression of the fatty acid transporter CD36 and the cholesterol transporter ABCA1 is significantly increased. In conclusion, placental sFlt-1 overexpression resulted in a reduction in the differentiation of the spongiotrophoblast into glycogen cells. These findings of a reduced exchange area of the labyrinth and glycogen stores, as well as decreased expression of glucose transporter, could contribute to the intrauterine growth restriction phenotype. All of these factors change the intrauterine availability of nutrients. Thus, we speculate that the alterations triggered by increased anti-angiogenesis strongly affect fetal outcome and programming. J. Cell. Biochem. 118: 1316-1329, 2017. © 2016 Wiley Periodicals, Inc.

Densitometer-Specific Differences in the Correlation Between Body Mass Index and Lumbar Spine Trabecular Bone Score.

Trabecular bone score (TBS) is a gray-level texture measure derived from lumbar spine dual-energy X-ray absorptiometry (DXA) images that predicts fractures independent of bone mineral density (BMD). Increased abdominal soft tissue in individuals with elevated body mass index (BMI) absorbs more X-rays during image acquisition for BMD measurement and must be accommodated by the TBS algorithm. We aimed to determine if the relationship between BMI and TBS varied between 2 major manufacturers' densitometers, because different densitometers accommodate soft tissues differently. We identified 1919 women and 811 men, participants of the Canadian Multicentre Osteoporosis Study, aged ≥40 yr with lumbar spine DXA scans acquired on GE Lunar (4 centers) or Hologic (3 centers) densitometers at year 10 of follow-up. TBS was calculated for L1-L4 (TBS iNsight® software, version 2.1). A significant negative correlation between TBS and BMI was observed when TBS measurements were performed on Hologic densitometers in men (Pearson r = -0.36, p <0.0001) and in women (Pearson r = -0.33, p <0.0001); significant correlations were not seen when TBS was measured on GE Lunar densitometers (Pearson r = 0.00 in men, Pearson r = -0.02 in women). Age-adjusted linear regression models confirmed significant interactions between BMI and densitometer manufacturer for both men and women (p < 0.0001). In contrast, comparable positive correlations were observed between BMD and BMI on both Hologic and GE Lunar densitometers in men and women. In conclusion, BMI significantly affects TBS values in men and women when measured on Hologic but not GE Lunar densitometers. This finding has implications for clinical and research applications of TBS, especially when TBS is measured sequentially on DXA densitometers from different manufacturers or when results from different machines are pooled for analysis.

Reduced Gene Dosage of Tfap2c Impairs Trophoblast Lineage Differentiation and Alters Maternal Blood Spaces in the Mouse Placenta.

Tfap2c is required for placental development and trophoblast stem cell maintenance. Deletion of Tfap2c results in early embryonic loss because of failure in placental development. We evaluated the effect of reduced Tfap2c expression on fetal outcome and placental development. Sixty percent of the heterozygous mice were lost directly after birth. Labyrinthine differentiation was impaired, as indicated by enhanced proliferation and inclusions of cobblestone-shaped cell clusters characterized by expression of Tfap2c and glycogen stores. Moreover, expression of marker genes such as Cdx2, Eomes, Gata3, and Ascl2 are decreased in the spongiotrophoblast and indicate a lowered stem cell potential. On Day 18.5 postcoitum, the labyrinth layer of Tfap2c(+/-) placentas exhibited massive hemorrhages in the maternal blood spaces; these hemorrhages might have contributed to the significantly reduced number of live-born pups. These morphological alterations were accompanied by a shift toward sinusoidal trophoblast giant cells as the cell subpopulation lining the maternal sinusoids and toward reduction in expression of the prolactin gene family member Prl2c2, a finding characteristic of the spiral arteries lining trophoblast cells. The trophoblast stem cells heterozygous for Tfap2c exhibited a reduction in the expression level of stem cell markers and in their proliferation and differentiation capacity but did not exhibit changes in marker genes of the trophoblast giant cell lineage. Taken together, these findings indicate that a reduction in the gene dosage of placental Tfap2c leads to morphological changes in the labyrinth at midgestation and in the maternal blood spaces during late pregnancy.

Injury prevention in male veteran football players - a randomised controlled trial using "FIFA 11+".

The warm-up programme "FIFA 11+" has been shown to reduce football injuries in different populations, but so far veteran players have not been investigated. Due to differences in age, skill level and gender, a simple transfer of these results to veteran football is not recommended. The purpose of this study was to investigate the preventive effects of the "FIFA 11+" in veteran football players. Twenty veteran football teams were recruited for a prospective 9-month (1 season) cluster-randomised trial. The intervention group (INT, n = 146; 45 ± 8 years) performed the "FIFA 11+" at the beginning of each training session, while the control group (CON, n = 119; 43 ± 6 years) followed its regular training routine. Player exposure hours and injuries were recorded according to an international consensus statement. No significant difference was found between INT and CON in overall injury incidence (incidence rate ratio [IRR]: 0.91 [0.64-1.48]; P = 0.89). Only severe injuries reached statistical significance with higher incidence in CON (IRR: 0.46 [0.21-0.97], P = 0.04). Regular conduction (i.e. once a week) of the "FIFA 11+" did not prevent injuries in veteran footballers under real training and competition circumstances. The lack of preventive effects is likely due to the too low overall frequency of training sessions.

DMP1 mutations in autosomal recessive hypophosphatemia implicate a bone matrix protein in the regulation of phosphate homeostasis.

Hypophosphatemia is a genetically heterogeneous disease. Here, we mapped an autosomal recessive form (designated ARHP) to chromosome 4q21 and identified homozygous mutations in DMP1 (dentin matrix protein 1), which encodes a non-collagenous bone matrix protein expressed in osteoblasts and osteocytes. Intact plasma levels of the phosphaturic protein FGF23 were clearly elevated in two of four affected individuals, providing a possible explanation for the phosphaturia and inappropriately normal 1,25(OH)2D levels and suggesting that DMP1 may regulate FGF23 expression.

Atypical Femoral Fractures: A Teaching Perspective.

This article provides an overview of atypical femoral fractures with a highlight on their radiographic findings. Potent antiresorptive agents such as bisphosphonates or denosumab have been associated with the development of such fractures. However, at this time, a causal association has not been conclusively established. Atypical femoral fractures are insufficiency fractures, which frequently present with bone pain. Early identification of characteristic radiographic features and withdrawal of antiresorptive therapy may prevent the development of completed atypical femoral fractures.

Injuries of veteran football (soccer) players in Germany.

There is a lack of injury data for the population of veteran football players. Therefore, a prospective study was conducted to investigate injury incidences and characteristics. Over one season, injuries and exposure of 18 teams (n = 265 players, age: 44.2±7.3 years, BMI: 26.6±3.2 kg/m(2)) were documented. Sixty-three players sustained a total of 88 injuries during the season. The incidence of training injuries (4.5 per 1000 hours) was significantly lower than of match injuries (24.7 per 1000 hours). The majority of injuries (n = 73; 83%) were located at the lower extremities, 52 (47%) were muscle injuries. The injury incidence of veteran football players is similar to other male football players of different skill levels and age groups, indicating a need for the implementation of preventive measures. Prevention programmes should consider the specific injury characteristics, with more muscle injuries in this population compared with younger football players.

Effect of Anticholinergic Medications on Falls, Fracture Risk, and Bone Mineral Density Over a 10-Year Period.

BACKGROUND: Many medications used in older adults have strong anticholinergic (ACH) properties, which may increase the risk of falls and fractures. Use of these medications was identified in a population-based Canadian cohort. OBJECTIVE: To identify the fall and fracture risk associated with ACH medication use. METHODS: Data collection and analysis were conducted at baseline, year 5, and year 10. Cross-sectional analyses were performed to examine associations between ACH medication use and falls. Time-dependent Cox regression was used to examine time to first nontraumatic fracture. Finally, change in bone mineral density (BMD) over 10 years was compared in ACH medication users versus nonusers. RESULTS: Strongly ACH medications were used by 618 of 7753 participants (8.0%) at study baseline, 592 (9.5%) at year 5, and 334 (7.7%) at year 10. Unadjusted ACH medication use was associated with falls at baseline (odds ratio = 1.50; 95% CI = 1.14-1.98; P = 0.004), but the association was no longer significant after covariate adjustment. Similar results occurred at years 5 and 10. ACH medication use was associated with increased incident fracture risk before (hazard ratio = 1.22; CI = 1.13-1.32; P < 0.001) but not after covariate adjustment. Mean (SD) change in femoral neck BMD T-score over 10 years, in those using ACH medications at both years 0 and 5, was -0.60 (0.63) in ACH users versus -0.49 (0.45) in nonusers (P = 0.041), but this was not significant after covariate adjustment. CONCLUSIONS: ACH medications were not found to be independently associated with an increased risk of falling, fractures, or BMD loss. Rather, factors associated with ACH medication use explained the apparent associations.

Prospectively measured 10-year changes in health-related quality of life and comparison with cross-sectional estimates in a population-based cohort of adult women and men.

PURPOSE: To prospectively assess changes in health-related quality of life (HRQOL) over 10 years, by age and sex, and to compare measured within-person change to estimates of change based on cross-sectional data. METHODS: Participants in the Canadian Multicentre Osteoporosis Study completed the 36-item short form (SF-36) in 1995/1997 and 2005/2007. Mean within-person changes for domain and summary components were calculated for men and women separately, stratified by 10-year age groups. Projected changes based on published age- and sex-stratified cross-sectional data were also calculated. Mean differences between the two methods were then estimated, along with the 95 % credible intervals of the differences. RESULTS: Data were available for 5,569/9,423 (59.1 %) of the original cohort. Prospectively collected 10-year changes suggested that the four physically oriented domains declined in all but the youngest group of men and women, with declines in the elderly men exceeding 25 points. The four mentally oriented domains tended to improve over time, only showing substantial declines in vitality and role emotional in older women, and all four domains in older men. Cross-sectional estimates identified a similar pattern of change but with a smaller magnitude, particularly in men. Correspondence between the two methods was generally high. CONCLUSIONS: Changes in HRQOL may be minimal over much of the life span, but physically oriented HRQOL can decline substantially after middle age. Although clinically relevant declines were more evident in prospectively collected data, differences in 10-year age increments of cross-sectional data may be a reasonable proxy for longitudinal changes, at least in those under 65 years of age. Results provide additional insight into the natural progression of HRQOL in the general population.

Choice of lumbar spine bone density reference database for fracture prediction in men and women: a population-based analysis.

The diagnosis of osteoporosis in men is controversial, although most studies demonstrate similar fracture rates for men and women with the same level of hip bone mineral density (BMD). Whether this applies to the lumbar spine is currently uncertain and has important implications with respect to choice of reference population for T-score calculation and osteoporosis diagnosis. This question was specifically addressed in the population-based Canadian Multicentre Osteoporosis Study cohort of 4745 women and 1887 men ages 50+ yr at the time of baseline lumbar spine dual energy x-ray absorptiometry. In up to 10 yr of observation, incident clinical major osteoporotic fractures occurred in 110 men (5.8%) vs 543 women (11.4%) (p < 0.001). Mean lumbar spine BMD in men was greater than in women, both among those with and those without incident major osteoporotic fracture (p < 0.001). Men were at slightly lower risk for incident major osteoporotic fracture than women for an equivalent lumbar spine BMD (age- and BMD-adjusted rate ratio 0.75, 95% confidence interval 0.60-0.93, p = 0.008) with similar findings after adjustment for the World Health Organization fracture risk assessment clinical risk factors or competing mortality. No significant sex difference in the BMD relationship was seen for vertebral fractures (clinical or radiographic) or for all fractures. In summary, this large population-based longitudinal cohort study found similar or lower fracture risk for men vs women after adjustment for absolute lumbar spine BMD and additional covariates. The least complicated model for describing fracture risk is therefore to use the same reference lumbar spine data for generating T-scores in men and women.