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
Population-based screening for osteoporosis is still controversial and has not been implemented. Non-participation in systematic screening was evaluated in 34,229 women age 65–81 years. ...Although participation rate was high, non-participation was associated with comorbidity, aging other risk factors for fractures, and markers of low social status, e.g., low income, pension, and living alone. A range of strategies is needed to increase participation, including development of targeted information and further research to better understand the barriers and enablers in screening for osteoporosis.
Introduction
Participation is crucial to the success of a screening program. The objective of this study was to analyze non-participation in Risk-stratified Osteoporosis Strategy Evaluation, a two-step population-based screening program for osteoporosis.
Methods
Thirty-four thousand two hundred twenty-nine women aged 65 to 81 years were randomly selected from the background population and randomized to either a screening group (intervention) or a control group. All women received a self-administered questionnaire designed to allow calculation of future risk of fracture based on FRAX. In the intervention group, women with an estimated high risk of future fracture were invited to DXA scanning. Information on individual socioeconomic status and comorbidity was obtained from national registers.
Results
A completed questionnaire was returned by 20,905 (61%) women. Non-completion was associated with older age, living alone, lower education, lower income, and higher comorbidity. In the intervention group, ticking “not interested in DXA” in the questionnaire was associated with older age, living alone, and low self-perceived fracture risk. Women with previous fracture or history of parental hip fracture were more likely to accept screening by DXA. Dropping out when offered DXA, was associated with older age, current smoking, higher alcohol consumption, and physical impairment.
Conclusions
Barriers to population-based screening for osteoporosis appear to be both psychosocial and physical in nature. Women who decline are older, have lower self-perceived fracture risk, and more often live alone compared to women who accept the program. Dropping out after primary acceptance is associated not only with aging and physical impairment but also with current smoking and alcohol consumption. Measures to increase program participation could include targeted information and reducing physical barriers for attending screening procedures.
Our objective is to evaluate an ultrasound probe for measurements of velocity and anisotropy in human cortical bone (tibia). The anisotropy of cortical bone is a known and mechanically relevant ...property in the context of osteoporotic fracture risk. Current in vivo quantitative ultrasound devices measuring the velocity of ultrasound in long bones can only be applied in the axial direction. For anisotropy measurements a second direction for velocity measurements preferably perpendicular to the axial direction is necessary. We developed a new ultrasound probe which permits axial transmission measurements with a simultaneous second perpendicular direction (tangential). Anisotropy measurements were performed on isotropic and anisotropic phantoms and two excised human female tibiae (age 63 and 82). Anisotropy ratios (AI; ratio of squared ultrasound velocities in the two directions) were for the isotropic phantom 1.06 ± 0.01 and for the anisotropic phantom 1.14 ± 0.03 (mean ± standard deviation). AI was 1.83 ± 0.29 in the tibia from the older donor and 1.37 ± 0.18 in the tibia from the younger donor. The AIs were in the expected range and differed significantly (p<0.05, t-test) between the tibiae. Measured sound velocities were reproducible (mean standard deviation of short time precision of both channels for phantom measurements 31 m/s) and in agreement with reported velocities of the phantom material. Our results document the feasibility of anisotropy measurements at long bones using a single probe. Further improvements in the design of the probe and tests in vivo are warranted. If this approach can be evaluated in vivo an additional tool for assessing the bone status is available for clinical use.
Summary A quantitative ultrasound (QUS) device for measurements at the proximal femur was developed and tested in vivo (Femur Ultrasound Scanner, FemUS). Hip fracture discrimination was as good as ...for DXA, and a high correlation with hip BMD was achieved. Our results show promise for enhanced QUS-based assessment of osteoporosis. Introduction Dual X-ray absorptiometry (DXA) at the femur is the best predictor of hip fractures, better than DXA measurements at other sites. Calcaneal quantitative ultrasound (QUS) can be used to estimate the general osteoporotic fracture risk, but no femoral QUS measurement has been introduced yet. We developed a QUS scanner for measurements at the femur (Femur Ultrasound Scanner, FemUS) and tested its in vivo performance. Methods Using the FemUS device, we obtained femoral QUS and DXA on 32 women with recent hip fractures and 30 controls. Fracture discrimination and the correlation with femur bone mineral density (BMD) were assessed. Results Hip fracture discrimination using the FemUS device was at least as good as with hip DXA and calcaneal QUS. Significant correlations with total hip bone mineral density were found with a correlation coefficient R ² up to 0.72 and a residual error of about one half of a T-score in BMD. Conclusions QUS measurements at the proximal femur are feasible and show a good performance for hip fracture discrimination. Given the promising results, this laboratory prototype should be reengineered to a clinical applicable instrument. Our results show promise for further enhancement of QUS-based assessment of osteoporosis.
•A new ultrasound device for the estimation of cortical bone porosity is presented.•Axial transmission velocities in different directions are measured.•The velocities measured reflect bone anisotropy ...which correlates with porosity.•The method was validated on cylindrical phantoms and phantoms with aligned pores.•Errors caused by phantom surface curvature could be compensated.
Quantitative ultrasound (QUS) measurements of trabecular bone are a useful tool for the assessment of osteoporotic fracture risk. However, cortical bone properties (e.g. porosity) have an impact on bone strength as well and thus current research is focused on QUS assessment of cortical bone properties. Simulation studies of ultrasound propagation through cortical bone indicate that anisotropy, calculated from the ratio of the velocities in axial and tangential directions, is correlated with porosity. However, this relationship is affected by error sources, specifically bone surface curvature and variability of probe positioning. With the aim of in vivo estimation of cortical porosity a new ultrasound device was developed, which sequentially measures velocities in 3 different directions (axial=0° and ±37.5°) using the axial transmission method. Measurements on planar porosity phantoms (0–25%) were performed to confirm the results of the afore mentioned simulation studies. Additionally, measurements on cylindrical phantoms without pores (min. radius=34mm for strongest curvature) were performed to estimate the influence of surface curvature on velocity measurements (the tibia bone surface is fairly flat but may show surface curvature in some patients). The velocities in the axial and ±37.5° directions were used to calculate an anisotropy index. The velocities measured on the porosity phantoms showed a decrease by −6.3±0.2m/s and −10.1±0.2m/s per percent increase in porosity in axial and ±37.5° directions, respectively. Surface curvature had an effect on the velocities measured in ±37.5° directions which could be minimized by a correction algorithm resulting in an error of 5m/s. The anisotropy index could be used to estimate porosity with an accuracy error of 1.5%. These results indicate that an estimation of porosity using velocity measurements in different directions might be feasible, even in bones with curved surface. These results obtained on phantom material indicate that the approach tested may be suited for porosity measurements on human tibia bone.
Summary
This Danish cross-sectional study (
n
= 20,905) showed that women aged 65–81 years generally underestimated fracture risk compared to absolute risk estimated by the FRAX® algorithm. ...Significant association was found between risk factors (e.g., previous fracture, parental hip fracture, and self-rated heath) and self-perceived fracture risk. Although women recognized the importance of some fracture risk factors, a number of significant risk factors appeared to be less well known.
Introduction
The aim of this study is to investigate women’s self-perceived fracture risk and potential factors associated with this and to compare self-perceived risk with absolute fracture risk estimated by FRAX® in women aged 65–80 years.
Methods
Data from 20,905 questionnaires from the ROSE study were analyzed. The questionnaire included 25 items on osteoporosis, risk factors for fractures, and self-perceived risk of fractures and enabled calculation of absolute fracture risk by FRAX®. Data were analyzed using bivariate tests and regression models.
Results
Women generally underestimated their fracture risk compared to absolute risk estimated by FRAX®. Women with risk factors for facture estimated their fracture risk significantly higher than their peers. No correlation between self-perceived risk and absolute risk was found. The ordered logistic regression model showed a significant association between high self-perceived fracture risk and previous fragility fracture, parental hip fracture, falls, self-rated heath, conditions related to secondary osteoporosis, and inability to do housework.
Conclusions
These women aged 65–81 years underestimated their risk of fracture. However, they did seem to have an understanding of the importance of some risk factors such as previous fractures, parental hip fracture and falls. Risk communication is a key element in fracture prevention and should have greater focus on less well-known risk factors. Furthermore, it is important to acknowledge that risk perception is not based solely on potential risk factors but is also affected by experiences from everyday life to personal history.
Abstract Type 2 diabetes mellitus increases skeletal fragility; however, the contributing mechanisms and the efficacy of bone-forming agents are unclear. We studied diabetes and parathyroid hormone ...(PTH) treatment effects on cortical porosity (Ct.Po), non-enzymatic glycation (NEG) and bone mechanics in Zucker diabetic fatty (ZDF) rats. Eleven-week old ZDF diabetic (DB) and non-diabetic (ND) rats were given 75 μg/kg PTH (1–84) or vehicle 5 days per week over 12 weeks. The right femora and L4 vertebrae were excised, micro-CT scanned, and tested in 3-point bending and uniaxial compression, respectively. NEG of the samples was determined using fluorescence. Diabetes increased Ct.Po (vertebra (vert): + 40.6%, femur (fem): + 15.5% vs. ND group, p < 0.05) but had no effect on NEG. PTH therapy reduced vertebral NEG in the ND animals only (− 73% vs untreated group, p < 0.05), and increased femoral NEG in the DB vs. ND groups (+ 63%, p < 0.05). PTH therapy had no effect on Ct.Po. Diabetes negatively affected bone tissue mechanics where reductions in vertebral maximum strain (− 22%) and toughness (− 42%) were observed in the DB vs. ND group (p < 0.05). PTH improved maximum strain in the vertebra of the ND animals (+ 21%, p < 0.05) but did not have an effect in the DB group. PTH increased femoral maximum strain (+ 21%) and toughness (+ 28%) in ND and decreased femoral maximum stress (− 13%) and toughness (− 27%) in the DB animals (treated vs. untreated, p < 0.05). Ct.Po correlated negatively with maximum stress (fem: R = − 0.35, p < 0.05, vert: R = − 0.57, p < 0.01), maximum strain (fem: R = − 0.35, p < 0.05, vert: R = − 0.43, p < 0.05) and toughness (fem: R = − 0.34, p < 0.05, vert: R = − 0.55, p < 0.01), and NEG correlated negatively with toughness at the femur (R = − 0.34, p < 0.05) and maximum strain at the vertebra (R = − 0.49, p < 0.05). Diabetes increased cortical porosity and reduced bone mechanics, which were not improved with PTH treatment. PTH therapy alone may worsen diabetic bone mechanics through formation of new bone with high AGEs cross-linking. Optimal treatment regimens must address both improvements of bone mass and glycemic control in order to successfully reduce diabetic bone fragility. This article is part of a Special Issue entitled “Bone and diabetes”.
Quantitative ultrasound (QUS) at the calcaneus has similar power as a bone mineral density (BMD)- measurement using DXA for the prediction of osteoporotic fracture risk. Ultrasound equipment is less ...expensive than DXA and free of ionizing radiation. As a mechanical wave, QUS has the potential of measuring different bone properties than dual X-ray absorptiometry (DXA,) which depends on X-ray attenuation and might be developed into a tool of comprehensive assessment of bone strength. However, site- specific DXA at the proximal femur shows best performance in the prediction of hip fractures. To combine the potential of QUS with measurements directly at the femur, we developed a device for in vivo QUS measurements at this site. Methods comprise ultrasound transmission through the bone, reflection from the bone surface, and backscat- ter from the inner trabecular structure. The complete area of the proximal femur can be scanned except at the femoral head, which interferes with the ilium. To avoid edge artifacts, a subregion of the proximal femur in the trochanteric region was selected as measurement region. First, in vivo measurements demonstrate a good signal to noise ratio and proper depiction of the proximal femur on an attenuation image. Our results demonstrate the feasibility of in vivo measurements. Further improvements can be expected by refinement of the scanning technique and data evaluation method to enhance the potential of the new method for the estimation of bone strength.
Summary
Quantitative ultrasound (QUS) measurement variables vary between European countries in a different way to hip bone mineral density. Standardization of data can be achieved through statistical ...approaches to reduce any between-center differences in QUS measurement variables. However, further validation of this method is required before it can be widely applied.
Introduction
European between-center differences in hip bone mineral density (BMD) have been shown to exist; however, little is known about the geographical heterogeneity of QUS measurement variables. We aimed to examine the differences in QUS variables between three different European countries.
Methods
Five calcaneal and phalangeal QUS devices in Sheffield, Aberdeen (UK), Kiel and Berlin (Germany), and three devices in Paris (France) were used to measure QUS variables in younger (
n
= 463, 20–39 years old) and older (
n
= 2,399, 55–79 years old) women participating in the European multicenter Osteoporosis and Ultrasound (OPUS) study. Broadband ultrasound attenuation, speed of sound, stiffness index, amplitude-dependent speed of sound, bone transmission time, and ultrasonic bone profiler index data were collected. Between-center differences were examined using ANOVA followed by post hoc Fisher's least significant difference tests, and ANCOVA with linear contrasts.
p
< 0.05 indicated statistical significance.
Results
Between-center differences in nonstandardized QUS measurement variables existed for younger (
p
= 0.0023 to
p
< 0.0001) and older women (
p
< 0.001). Anthropometric characteristics exerted a significant influence on nonstandardized data (
p
= 0.045 to
p
< 0.001). However, following statistical standardization, based on height and weight or based on measurements made in young people, geographical heterogeneity in QUS measurement variables was no longer apparent.
Conclusions
QUS measurement variables vary between European countries in a different way to those for hip BMD. Standardization of data can be achieved through statistical approaches to reduce any between-center differences in QUS measurement variables. However, further validation of this method is required before it can be widely applied.
Summary We observed higher proximal femur bone mineral density (BMD) in European women compared to average values derived from US Caucasian women in the National Health and Nutrition Examination ...Survey (NHANES) study. Across European centres, Parisian women had lower proximal femur BMD compared to women from Kiel or Sheffield. Introduction Proximal femur BMD of US adults (NHANES III) may not accurately reflect that of European women. We examined the heterogeneity of BMD across European and US Caucasian women and across different European populations. Methods Proximal femur BMD was measured in women ages 20-39 years (n = 258) and 55-79 years (n = 1,426) from three European centres. Cross-calibrated BMD for total hip, femoral neck, trochanter and intertrochanter were examined. International variation in BMD was assessed by comparing means and SDs in the European data with those from the US NHANES III study. European populations were stratified into 5-year age bands to establish individual centre reference intervals. Between-centre differences were assessed using ANOVA and post hoc Fisher's least significant difference tests. Results European women had higher BMD than US women: The differences were 7.1% to 14.2% (p < 0.001) and 0% to 3.9% (p < 0.05) in the older and younger women, respectively. Standard deviations for BMD at the different sites were comparable to those for US women. Among older, but not younger European women, proximal femur BMD was significantly lower in French women (Paris) than in women from Germany (Kiel) or the UK (Sheffield) (difference = 5.0% to 9.6%, p < 0.05). Conclusions International variation in hip BMD does exist, with international and between-centre differences being less evident at the femoral neck.
