Tieteelliset referenssit - Bindex

”Bindex® screening can be shown to be cost-effective compared to current practice.”

Lewiecki M. (2020) Pulse-echo Ultrasound Identifies Caucasian and Hispanic Women at Risk for Osteoporosis

Background: Pulse-echo ultrasonography (PEUS) is a novel ultrasound method that measures the thickness of cortical bone at peripheral skeletal sites with a handheld device connected to a personal computer using proprietary software. Previous studies have shown a significant correlation between density index (DI), a PEUS-derived parameter, and bone mineral density (BMD) measured by dual-energy X-ray absorptiometry at the hip. DI thresholds that discriminate patients likely to have osteoporosis with 90% sensitivity and 90% specificity have been established in a population of Caucasian women in Finland and validated in a study of predominately Caucasian women in the state of Minnesota in the USA. The DI thresholds have not previously been evaluated in non-Caucasian populations.

Methodology: This study aimed to determine whether previously established DI thresholds in Caucasian women require adjustment in Hispanic women. PEUS measurements at the proximal tibia and dual-energy X-ray absorptiometry BMD at the hip were evaluated in Caucasian and Hispanic women at a single investigative site in Albuquerque, New Mexico, USA. DI was calculated for each patient and compared with BMD. The performance of DI threshold values for these populations was compared.

Results: The study enrolled 293 postmenopausal women (153 Caucasian, 140 Hispanic) with and without osteoporosis. The sensitivity and specificity for DI thresholds to distinguish women with total hip or femoral neck T-score ≤ -2.5 or > -2.5 was similar in Caucasians (sensitivity 80%, specificity 86%) and Hispanics (sensitivity 80%, specificity 91%).

Conclusions: The findings of this study confirm the utility of previously established DI thresholds to identify women who are likely or unlikely to have osteoporosis and suggest that the same thresholds can be used for postmenopausal Caucasian and Hispanic women.

https://pubmed.ncbi.nlm.nih.gov/32527649/

van den Berg P. (2020) The use of pulse-echo ultrasound in women with a recent non-vertebral fracture to identify those without osteoporosis and/or a subclinical vertebral fracture: a pilot study

A pilot study on the use of P-EU to identify patients without osteoporosis and/or a subclinical vertebral fracture after a recently sustained non-vertebral fracture (NVF).

Introduction: Screening with portable devices at emergency departments or plaster rooms could be of interest to limit referrals for dual X-ray absorptiometry (DXA) and vertebral fracture assessment (VFA). We calculated the number of negative tests for osteoporosis and/or subclinical vertebral fractures (VFs) using pulse-echo ultrasonometry (P-UE) at different thresholds.

Patients and methods: In this cross-sectional study, 209 consecutive women of 50-70 years with a recent non-vertebral fracture (NVF) were studied at the Fracture Liaison Service (FLS) of one hospital. All women received DXA/VFA and P-EU (Bindex®) assessments. Various P-EU thresholds (based on the density index (DI, g/cm2)) were analyzed to calculate the best balance between true negative (indeed no osteoporosis and/or subclinical VF) and false negative tests (osteoporosis and/or subclinical VF according to DXA/VFA).

Results: Eighty-three women had osteoporosis (40%) and 17 women at least one VF (8%). Applying the manufacturer’s recommended P-EU threshold (DI 0.844 g/cm2) being their proposed cut-off for not having hip osteoporosis resulted in 77 negative tests (37%, 31% true negative and 6% false negative tests). A DI of 0.896 g/cm2 resulted in 40 negative tests (19.3%) (38 true negative (18.3%) and 2 false negative tests (1.0%)).

Conclusion: The application of P-EU enables the identification of a substantial proportion of women with recent non-vertebral fractures at the FLS who would not need a DXA/VFA referral because they had no osteoporosis and/or subclinical vertebral fractures. The most conservative P-EU threshold resulted in 18.3% true negative tests verified by DXA/VFA against 1% false negative test results.

https://pubmed.ncbi.nlm.nih.gov/32291527/

Nazari-Farsani S. (2020) Bone Mineral Density and Cortical-Bone Thickness of the Distal Radius Predict Femoral Stem Subsidence in Postmenopausal Women

Background: The distal radius is an optional site for evaluation of bone quality in postmenopausal women before cementless total hip arthroplasty. We hypothesized that dual-energy X-ray absorptiometry (DXA) and pulse-echo ultrasonometry of the distal radius may help discriminate subjects at high risk of femoral stem subsidence.

Methods: A prospective cohort of postmenopausal women with primary hip osteoarthritis underwent total hip arthroplasty with implantation of a parallel-sided femoral stem. Postoperative stem migration was measured using radiostereometric analysis. Preoperatively, subjects had multisite DXA measurement of bone mineral density (BMD) and pulse-echo ultrasonometry of the cortical-bone thickness. The diagnostic abilities of these methods to discriminate <2 mm and ≥2 mm femoral stem subsidence were tested.

Results: The accuracy of the distal radius BMD and cortical-bone thickness of the distal radius were moderate (area under the curve, 0.737 and 0.726, respectively) in discriminating between <2 mm and ≥2 mm stem subsidence. Women with low cortical-bone thickness of the radius were more likely (odds ratio = 6.7; P = .002) to develop stem subsidence ≥2 mm. These subjects had lower total hip BMD (P = .007) and reduced thickness of the medial cortex of the proximal femur (P = .048) with lower middle (P < .001) and distal (P = .004) stem-to-canal fill ratios.

Conclusion: Femoral stem stability and resistance to subsidence are sensitive to adequate bone stock and unaltered anatomy. DXA and pulse-echo ultrasonometry of the distal radius may help discriminate postmenopausal women at high risk of stem subsidence.

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Soini E (2018) Cost-effectiveness of pulse-echo ultrasonometry in osteoporosis management

Purpose: Osteoporosis is asymptomatic morbidity of the elderly which develops slowly over several years. Osteoporosis diagnosis has typically involved Fracture Risk Assessment (FRAX) followed by dual energy X-ray absorptiometry (DXA) in specialist care. Point-of-care pulse-echo ultrasound (PEUS) was developed to overcome DXA-related access issues and to enable faster fracture prevention treatment (FPT) initiation. The objective of this study was to evaluate the cost-effectiveness of two proposed osteoporosis management (POMs: FRAX→PEUS-if-needed→DXA-if-needed→FPT-if-needed) pathways including PEUS compared with the current osteoporosis management (FRAX→DXA-if-needed→FPT-if-needed).

Materials and methods: Event-based probabilistic cost–utility model with 10-year duration for osteoporosis management was developed. The model consists of a decision tree for the screening, testing, and diagnosis phase and is followed by a Markov model for the estimation of incidence of four fracture types and mortality. Five clinically relevant patient cohorts (potential primary FPT in women aged 75 or 85 years, secondary FPT in women aged 65, 75, or 85 years) were modeled in the Finnish setting. Generic alendronate FPT was used for those diagnosed with osteoporosis, including persistence overtime. Discounted (3%/year) incremental cost-effectiveness ratio was the primary outcome. Discounted quality-adjusted life-years (QALYs), payer costs (year 2016 value) at per patient and population level, and cost-effectiveness acceptability frontiers were modeled as secondary outcomes.

Results: POMs were cost-effective in all patient subgroups with noteworthy mean per patient cost savings of €121/76 (ranges €107–132/52–96) depending on the scope of PEUS result interpretation (test and diagnose/test only, respectively) and negligible differences in QALYs gained in comparison with current osteoporosis management. In the cost-effectiveness acceptability frontiers, POMs had 95%–100% probability of cost-effectiveness with willingness to pay €24,406/QALY gained. The results were robust in sensitivity analyses. Even when assuming a high cost of PEUS (up to €110/test), POMs were cost-effective in all cohorts.
Conclusion: The inclusion of PEUS to osteoporosis management pathway was cost-effective.

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Karjalainen JP (2018) Pulse-echo ultrasound method for detection of post-menopausal women with osteoporotic BMD

We lack effective diagnostics of osteoporosis at the primary health care level. An ultrasound device was used to identify subjects in the osteoporotic range as defined by DXA. A case finding strategy combining ultrasound results with DXA measurements for patients with intermediate ultrasound results is presented.

We lack effective screening and diagnostics of osteoporosis at primary health care. In this study, a pulse-echo ultrasound (US) method is investigated for osteoporosis screening.

A total of 1091 Caucasian women (aged 50–80 years) were recruited for the study and measured with US in the tibia and radius. This method measures cortical thickness and provides an estimate of bone mineral density (BMD) and density index (DI). BMD assessment of the hip was available for 988 women. A total of 888 women had one or more risk factors for osteoporosis (OPsusp), and 100 women were classified healthy. Previously determined thresholds for the DI were evaluated for assessment of efficacy of the technique to detect hip BMD at osteoporotic range (T-score at or below − 2.5).

In the OPsusp group, the application of thresholds for the DI showed that approximately 32%of the subjects would require an additional DXA measurement. The multi-site ultrasound (US) measurement-based DI showed 93.7% sensitivity and 81.6% specificity, whereas the corresponding values for single-site US measurement-based DI were 84.7 and 82.0%, respectively. The ultrasound measurements showed a high negative predictive value 97.7 to 99.2%in every age decade examined (ages 50–59, 60–69, 70–79 years).

The study data demonstrate that a strategy of combining ultrasound measurement with added DXA measurements in cases with intermediate ultrasound results (about 30%) can be useful for identifying subjects at risk for a low bone mineral density in the osteoporotic range.

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Schousboe JT (2016) Prediction of hip osteoporosis by DXA using a novel pulse-echo ultrasound device, Osteoporosis International

Pulse-echo ultrasonometry can be used as a pre-screen for hip osteoporosis before dual-energy x-ray absorptiometry (DXA), potentially allowing DXA to be avoided for the majority of post-menopausal women. Pulse-echo ultrasound measures of tibia cortical thickness are also associated with radiographically confirmed prior fractures, independent of femoral neck bone mineral density.

Five hundred fifty-five post-menopausal women age 50 to 89 had femoral neck and total hip BMD measured by dual-energy x-ray absorptiometry (DXA), and pulse-echo ultrasound measures of distal radius, proximal tibia, distal tibia cortical thickness, and multi- and single-site density indices (DI). Using previously published threshold ultrasound values, we estimated the proportion of women who would avoid a follow-up DXA after pulse-echo ultrasonometry, and the sensitivity and specificity of this for the detection of hip osteoporosis. Logistic regression models were used to estimate the associations of pulse-echo ultrasound measures with radiographically confirmed clinical fractures within the prior 5years.

Using multi-site and single-site DI measures, follow-up DXA could be avoided for 73 and 69% of individuals, respectively, while detecting hip osteoporosis with 80-82% sensitivity and 81% specificity. Radiographically confirmed prior fracture was associated with ultrasound measures of single-site DI (odds ratio (OR) 1.55, 95% confidence interval (CI). 1.06 to 2.26) and proximal tibia cortical thickness (OR 1.47, 95% CI 1.10 to 1.96), adjusted for age, body mass index, and femoral neck BMD.

Pulse-echo ultrasonometry can be used as an initial screening test for hip osteoporosis. Prospective studies of how well pulse-echo ultrasound measures predict subsequent clinical fractures are warranted.

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Karjalainen JP (2016) Sensitivity and specificity of osteoporosis diagnostics at primary healthcare with Bindex®, WCO-IOF-ESCEO

A new ultrasound based point of care device (Bindex®) has been recently introduced for osteoporosis (OP) screening and diagnostics at primary healthcare. Bindex® measures cortical thickness and determines parameter called density index (DI). Thresholds (90% sensitivity and specificity, triage approach) for DI in OP assessment have been determined in Finnish Caucasian population along the International Society of Clinical Densitometry (ISCD) guidelines. In this study, the sensitivity and specificity are assessed in data set combining three independent trials.

A total of 1830 Caucasian females participated the study (age 67.2 ± 8.9 years). Subjects were measured with dual energy x-ray absorptiometry (DXA) to determine bone mineral density (BMD) at proximal femur. Further, the cortical thickness was measured at three locations (distal radius, distal and proximal tibia) with Bindex®. Subjects were diagnosed with OP when T-score at femoral neck or total proximal femur was below -2.5 (NHANES III reference database). A subgroup of 1344 subjects was formed in which the subjects with T-score -2.1 – -2.9 were removed due to the precision error in T-score values and uncertainty of osteoporosis/healthy status. In this subgroup, OP was diagnosed when T-score was at or below -2.9. Density index was calculated either by using measurement at one location (DI1, proximal tibia) or all three locations (DI3).

A total of 70 to 73% of the subjects could be directly diagnosed by using Bindex® measurement. Sensitivity in OP diagnostics was 82% and 87% for DI1 and DI3, respectively. Specificity was 83% for both DI1 and DI3. In the subgroup, sensitivity in OP diagnostics was 90% and 93% for DI1 and DI3, respectively. Specificity was 87% for both DI1 and DI3.

The suggested thresholds for the DI were tested in a large population and performance of the technique seems consistent when data from several studies were combined. The ultrasound based Bindex measurement for osteoporosis detection shows good performance for OP detection at primary care level.

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Karjalainen JP (2015) New Method for Point-of-care Osteoporosis Screening and Diagnostics, Osteoporosis International

Due to the lack of diagnostics in primary health care, over 75% of osteoporotic patients are not diagnosed. A new ultrasound method for primary health care is proposed. Results suggest applicability of ultrasound method for osteoporosis diagnostics at primary health care.

A total of 572 Caucasian women (age 20 to 91years) were examined using pulse-echo US measurements in the tibia and radius. This method provides an estimate of bone mineral density (BMD), i.e. density index (DI). Areal BMD measurements at the femoral neck (BMDneck) and total hip (BMDtotal) were determined by using axial dual-energy X-ray absorptiometry (DXA) for women older than 50years of age (n = 445, age = 68.8 ± 8.5years). The osteoporosis thresholds for the DI were determined according to the International Society for Clinical Densitometry (ISCD). Finally, the FRAX questionnaire was completed by 425 participants.

Osteoporosis was diagnosed in individuals with a T-score -2.5 or less in the total hip or femoral neck (n = 75). By using the ISCD approach for the DI, only 28.7% of the subjects were found to require an additional DXA measurement. Our results suggest that combination of US measurement and FRAX in osteoporosis management pathways would decrease the number of DXA measurements to 16% and the same treatment decisions would be reached at 85.4% sensitivity and 78.5% specificity levels.

The present results demonstrate a significant correlation between the ultrasound and DXA measurements at the proximal femur. The thresholds presented here with the application to current osteoporosis management pathways show promise for the technique to significantly decrease the amount of DXA referrals and increase diagnostic coverage; however, these results need to be confirmed in future studies.

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