Abstract Introduction A diagnostic gap exists in the current dual photon X-ray absorptiometry (DXA) based diagnostic approach to osteoporosis. Other diagnostic devices have been developed, but no ...comprehensive review concerning the applicability of these diagnostic devices for population-based screening have been performed. Material and
m
ethods A systematic review of Embase, Medline and the Cochrane Central Register for Controlled Trials was performed for population-based studies that focused on technical methods that could either indicate bone mineral density (BMD) by DXA, substitute for DXA in prediction of fracture risk, or that could have an incremental value in fracture prediction in addition to DXA. Quality of included studies was rated by QUADAS 2. Results Many other technical devices have been tested in a population-based setting. Five studies aiming to indicate BMD and 17 studies aiming to predict fractures were found. Overall, the latter studies had higher methodological quality. The highest number of studies was found for quantitative ultrasound (QUS). The ability to indicate BMD or predict fractures was moderate to minor for all examined devices, using reported
a
rea
u
nder the
c
urve (AUC) of Receiver Operating Characteristic curves values as standard. Conclusions Of the methods assessed, only QUS appears capable of perhaps replacing DXA as standalone examination in the future whilst radiographic absorptiometry could provide important information in areas with scarcity of DXA. QUS may be of added value even after DXA has been performed. Evaluation of proposed cutoff-values from population-based studies in separate population-based cohorts is still lacking for most examination devices.
Summary
Use of antiosteoporotic medication in the population-based, risk-stratified osteoporosis strategy evaluation (ROSE) screening study, comparing the use of FRAX followed by DXA with usual care, ...was examined. Screening increased the overall use of medication. Being recommended treatment by the hospital and higher age increased the likelihood of starting medication, but, nevertheless, a large percentage opted not to start treatment.
Introduction
The aim of the study was to examine the impact on medication prescription, adherence, and persistence of osteoporotic medicine in the randomized population-based ROSE screening study for osteoporosis.
Methods
The Danish ROSE study included a population-based random sample of women aged 65–81 years randomized to either a two-step screening program consisting of FRAX followed by DXA for high-risk participants or opportunistic screening for osteoporosis (usual care). This sub-study on the intention-to-treat population examined the impact of the screening program on antiosteoporotic medication redemption rates, adherence, and persistence using Danish registers.
Results
A total of 30,719 of 34,229 women were treatment-naïve. Significantly more participants in the screening group started on antiosteoporotic medication, but no differences in adherence and persistence rates were found. Higher age was associated with a higher likelihood of starting medication. A low Charlson comorbidity score (= 1) was associated with higher treatment initiation but lower adherence and persistence of antiosteoporotic treatment. A total of 31.7% of participants advised to initiate treatment did not follow the advice.
Conclusions
Screening for osteoporosis using FRAX followed by DXA increased the overall use of antiosteoporotic medication in the screening group without differences in adherence and persistence rates. A large percentage of participants advised to initiate treatment did nevertheless fail to do so.
Summary
The Risk-stratified Osteoporosis Strategy Evaluation (ROSE) study investigated the effectiveness of a two-step screening program for osteoporosis in women. We found no overall reduction in ...fractures from systematic screening compared to the current case-finding strategy. The group of moderate- to high-risk women, who accepted the invitation to DXA, seemed to benefit from the program.
Introduction
The purpose of the ROSE study was to investigate the effectiveness of a two-step population-based osteoporosis screening program using the Fracture Risk Assessment Tool (FRAX) derived from a self-administered questionnaire to select women for DXA scan. After the scanning, standard osteoporosis management according to Danish national guidelines was followed.
Methods
Participants were randomized to either screening or control group, and randomization was stratified according to age and area of residence. Inclusion took place from February 2010 to November 2011. Participants received a self-administered questionnaire, and women in the screening group with a FRAX score ≥ 15% (major osteoporotic fractures) were invited to a DXA scan. Primary outcome was incident clinical fractures. Intention-to-treat analysis and two per-protocol analyses were performed.
Results
A total of 3416 fractures were observed during a median follow-up of 5 years. No significant differences were found in the intention-to-treat analyses with 34,229 women included aged 65–80 years. The per-protocol analyses showed a risk reduction in the group that underwent DXA scanning compared to women in the control group with a FRAX ≥ 15%, in regard to major osteoporotic fractures, hip fractures, and all fractures. The risk reduction was most pronounced for hip fractures (adjusted SHR 0.741,
p
= 0.007).
Conclusions
Compared to an office-based case-finding strategy, the two-step systematic screening strategy had no overall effect on fracture incidence. The two-step strategy seemed, however, to be beneficial in the group of women who were identified by FRAX as moderate- or high-risk patients and complied with DXA.
Summary
To evaluate the case-finding strategy for osteoporosis in Norway, a questionnaire concerning risk factors for osteoporosis and history of osteodensitometry was mailed to a population-based ...cohort of 6000 men and 6000 women. Suboptimal examination rates among high risk and reallocation of scanning capacity to seemingly low-risk individuals was found.
Purpose
In Norway, a case-finding strategy for osteoporosis has been used. No data exist regarding the efficacy of this approach. The aim was to examine the prevalence of risk factors for osteoporosis and factors related to the use of dual X-ray absorptiometry (DXA) in Norway.
Methods
Questionnaires regarding previous history of DXA, risk factors for osteoporosis and fracture were sent to an age-stratified, nationwide cross-sectional sample of 6000 men and 6000 women aged 40–90 years, drawn from the Norwegian Civil Registration System.
Results
Valid responses (6029) were included. Twenty-two point three percent of women and 3.8 % of men had been examined by DXA. Suboptimal examination rates among high risk (e.g., current/previous glucocorticoid treatment or previous low-energy fracture) and reallocation of scanning capacity to seemingly low-risk individuals was found. Of all DXA, 19.5 % were reported by women without any risk factor for osteoporosis, similarly by 16.2 % of men. Distance to DXA facilities and current smoking were inversely related to probability of reporting a DXA.
Conclusions
Suboptimal examination rates among high risk and reallocation of scanning capacity to seemingly low-risk individuals were found. Distance to DXA, current smoking, and male sex constituted possible barriers to the case-finding strategy employed. Cheap and more available diagnostic tools for osteoporosis are needed, and risk stratification tools should be employed more extensively.
Summary
There is a need of studies exploring the link between socioeconomic status and DXA scans and osteoporotic fracture, which was the aim of the present study. No differences in socioeconomic ...status and risk of osteoporotic fractures were found. However, women with further/higher education and higher income are more often DXA-scanned.
Introduction
Lower socioeconomic status is known to be associated with a range of chronic conditions and with access to health care services. The link between socioeconomic status and the use of DXA scans and osteoporotic fracture, however, needs to be explored more closely. Therefore, the aim of this study was to examine the relationship between socioeconomic status and both DXA scan utilization and major osteoporotic fractures (MOF) using a population-based cohort of Danish women and national registers.
Methods
The study included 17,155 women (65–81 years) sampled from the Risk-stratified Osteoporosis Strategy Evaluation study (ROSE). Information on socioeconomic background, DXA scans, and MOFs was retrieved from national registers. Competing-risk regression analyses were performed. Mean follow-up was 4.8 years.
Results
A total of 4245 women had a DXA scan (24.7%) and 1719 (10.0%) had an incident MOF during follow-up. Analyses showed that women with basic education had a lower probability of undergoing DXA scans than women with further or higher education (greater than upper secondary education and vocational training education) (subhazard ratio (SHR) = 0.82; 95% CI 0.75–0.89, adjusted for age and comorbidity). Moreover, women with disposable income in the low and medium tertiles had a lower probability of undergoing DXA scans than women in the high-income tertile (SHR = 0.90; 95% CI 0.84–0.97 and SHR = 0.88, 95% CI 0.82–0.95, respectively, adjusted for age and comorbidity). No association between socioeconomic background and probability of DXA was found in adjusted analyses.
Conclusion
The study found no differences in risk of osteoporotic fractures depending on socioeconomic status. However, women with further or higher education as well as higher income are more often DXA-scanned.
Extrapyramidal symptoms (EPS) are seen in 50-75% of patients treated with typical antipsychotics and are a cause of treatment failure in at least 30% of the patients. Using atypical antipsychotics, ...the EPS incidence is lower, but a low-dosage strategy using typical antipsychotics is also known to cause fewer EPS. What conclusions can be drawn for the daily clinical practice? A naturalistic study including all schizophrenic inpatients in a psychiatric ward (n=123) analysed the effects of treatment concerning positive/negative symptoms, EPS, number of days to re-hospitalization and inpatient-days in the year after baseline admittance, using atypical and typical antipsychotics as recommended by the Danish Society of Psychiatry. The incidence of EPS was significantly higher in patients who were treated with typical antipsychotics in relation to atypical antipsychotics (46% vs. 12%, P<0.001). Patients with EPS had significantly more negative symptoms and a poorer level of function at discharge. Nevertheless, no difference regarding re-hospitalization and inpatient-days was found, whether the patient was treated with typical or atypical antipsychotics. However, it is important to underline that patients treated with atypical oral antipsychotic do as well as patients on typical depot antipsychotics.
Population-based reference values for peak bone mass density in Danish men. BMD of total hip (1.078 +/- 0,14 g/cm2) differed significantly from values from National Health and Nutrition Examination ...Survey III and of total lumbar spine ((1.073 +/- 0.125 g/cm2) differed significantly from Hologic values.
Geographic, ethnic, and socio-economic factors are known to affect bone mineral density (BMD) and peak bone mass significantly. Reference values for male peak bone mass are scarce, and the diagnosis of male osteoporosis often relies on values provided by producers of dual-energy X-ray absorptiometry (DXA) equipment.
The aim of the present study was 1) to establish population-based reference values for BMD in young men and 2) to study subgroups based on variables with suspected impact on bone metabolism. We included 783 young Caucasian men aged 20 to 30 years in the Odense Androgen Study (OAS).
Peak BMD was attained within the third decade. Obesity (BMI > 30 kg/m2) was associated with higher BMD. Abuse of anabolic steroids as well as chronic illness was associated with lower BMD. Our population-based reference values for BMD of the total hip (1.078 +/- 0.14 g/cm2) differed significantly from published values from National Health and Nutrition Examination Survey III for non-Hispanic white men, while BMD of total lumbar spine (1.073 +/- 0.125 g/cm2) differed significantly from Hologic reference values.
Locally derived reference values are important to avoid false positive or false negative findings during work-up in patients evaluated for osteoporosis.
PICK1 is a neuronal scaffolding protein containing a PDZ domain and an auto-inhibited BAR domain. BAR domains are membrane-sculpting protein modules generating membrane curvature and promoting ...membrane fission. Previous data suggest that BAR domains are organized in lattice-like arrangements when stabilizing membranes but little is known about structural organization of BAR domains in solution. Through a small-angle X-ray scattering (SAXS) analysis, we determine the structure of dimeric and tetrameric complexes of PICK1 in solution. SAXS and biochemical data reveal a strong propensity of PICK1 to form higher-order structures, and SAXS analysis suggests an offset, parallel mode of BAR-BAR oligomerization. Furthermore, unlike accessory domains in other BAR domain proteins, the positioning of the PDZ domains is flexible, enabling PICK1 to perform long-range, dynamic scaffolding of membrane-associated proteins. Together with functional data, these structural findings are compatible with a model in which oligomerization governs auto-inhibition of BAR domain function.
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•The PDZ domains are far apart and flexible with respect to the BAR domain•PICK1 forms higher oligomeric species in solution•The N-BAR domain is directly involved in the parallel, offset oligomerization mode•Oligomerization is likely to regulate BAR domain auto-inhibition
Karlsen et al. present structures of PICK1 demonstrating that the protein binding PDZ domains are flexible with respect to the membrane binding BAR domain enabling long-range scaffolding interactions. Furthermore, PICK1 oligomerization involves an offset, parallel arrangement of the BAR domains, possibly governing BAR domain auto-inhibition.
This review looked at the effect of cataract surgery on the regulation of circadian rhythms and compared the effect of blue light–filtering and clear intraocular lenses (IOLs) on circadian rhythms. A ...systematic review and metaanalysis were performed, and the level of evidence was evaluated based on the principles described in the Grading of Recommendations Assessment, Development, and Evaluation system. A literature search of PubMed, Embase, and Cochrane Library databases was performed, as well as a search for unpublished trials at the U.S. National Institutes of Health Clinical Trials web site. Trials that reported the effect of cataract surgery on circadian rhythms were included. Outcomes were the Pittsburgh Sleep Quality Index (PSQI) global score, number of poor sleepers, Epworth Sleepiness Score, sleep efficiency, and mean concentration of melatonin. Cataract surgery improved regulation of circadian rhythms measured by the PSQI questionnaire, but the clinical relevance is uncertain. There was no difference between the effect of the 2 IOL types. Financial Disclosure No author has a financial or proprietary interest in any material or method mentioned.
The fields of DNA and RNA nanotechnology have established nucleic acids as valuable building blocks for functional nanodevices with applications in nanomedicine. Here, a simple method for designing ...and assembling a 3D scaffolded RNA origami wireframe structure with intrinsic functioning small interfering RNAs (siRNAs) embedded is introduced. Uniquely, the method uses an mRNA fragment as scaffold strand, which is folded by sequence‐complementarity of nine shorter synthetic strands. High‐yield production of the intended 3D structure is verified by transmission electron microscopy (TEM). Production of functional siRNAs is facilitated by incorporating recognition sites for Dicer at selected locations in the structure, and efficient silencing of a target reporter gene is demonstrated.
A 3D scaffolded RNA origami wireframe structure with intrinsic small interfering RNAs (siRNAs) is characterized by transmission electron microscopy (TEM) and demonstrated to efficiently silence a target reporter gene when transfected into H1299 cells. Production of functional siRNAs is facilitated by implementing recognition sites for Dicer at selected locations in the structure.
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