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.

Effects of non-optimal focusing on dual-frequency ultrasound measurements of bone.

In pulse-echo (PE) ultrasound measurements, the use of focused transducers is desirable for quantitative assessment of bone characteristics because of the attenuation in the overlying soft tissues. However, the variable thickness and composition of the soft tissue overlying bone affect the focal depth of the ultrasound beam and induce errors into the measurements. To compensate for the attenuation-related effects caused by the interfering soft tissue (i.e., fat and lean tissue), a dual-frequency ultrasound (DFUS) technique was recently introduced. The aim of this study was to investigate the effect of non-optimal focal depth of the ultrasound beam on the determination of the integrated reflection coefficient (IRC) of bone when overlaid by an interfering layer composed of oil and water. The feasibility of the DFUS-based correction of the IRC was evaluated through numerical simulations and experimental measurements. Even when the interfering layer-bone interface was out of focus, the total thickness of the interfering layer could be accurately determined with the technique. However, based on the simulations, the errors in the determination of the composition of the interfering layer increased (0.004 to 113.8%) with the increase in distance between the interfering layer-bone interface and the focus of the ultrasound beam. Attenuation compensation, based on the true composition of the interfering layer, resulted in an average relative error of 22.3% in the IRC values calculated from the simulations. Interestingly, the attenuation compensation with the interfering layer composition estimated using the DFUS technique resulted in a smaller average relative error of 14.9% in the IRC values. The simulations suggest that DFUS can reduce the errors induced by soft tissue in bone PE ultrasound measurements. The experimental measurements indicate that the accuracy of the IRC measurements is rather similar when using DFUS correction or correction based on the true composition of the interfering layer. However, the results suggest that accurate determination of soft tissue composition may be difficult without optimal focusing of the ultrasound beam on the soft tissue-bone interface.

Numerical analysis of uncertainties in dual frequency bone ultrasound technique.

Quantitative ultrasound (QUS) measurements are used in the diagnostics of osteoporosis. However, the variation in the thickness and composition of the overlying soft tissue causes significant errors to the bone QUS parameters and diminishes the reliability of the technique in vivo. Recently, the dual frequency ultrasound (DFUS) technique was introduced to minimize the errors related to soft tissue effects. In this study, the significance of soft tissue induced errors and their elimination with the DFUS technique were simulated using the finite difference time domain technique. Furthermore, we investigated the potential of the DFUS corrected integrated reflection coefficient (IRC) of bone to detect changes in the cortical bone density. The effects of alterations in the thickness of fat and lean tissue layers and the inclination between the soft-tissues and between the soft tissue-bone layers were simulated. When the angle of the soft tissue interface was zero, i.e., perpendicular to the incident ultrasound beam, the DFUS-calculated soft tissue composition correlated highly linearly with the true soft tissue composition. The inclination between the soft tissue-bone layers was found to be critical. Even a 2-degree inclination between the soft tissue and the bone surface induced an almost 18% relative error in the corrected IRC. Increasing the inclination between the soft tissue layers increased the error in the DFUS-calculated lean and fat tissue thickness. This error was especially significant at inclination angles greater than 20 degrees. The significant soft tissue induced errors in IRC values (>300 %) could be effectively minimized (<10%) by means of the DFUS correction. Importantly, after the DFUS correction, physiologically relevant variation in the cortical bone density could be detected (p<0.05).

Ultrasound backscatter imaging provides frequency-dependent information on structure, composition and mechanical properties of human trabecular bone.

The strength as well as the acoustic properties of trabecular bone are determined by its structure and composition. Consequently, tissue structure and compositional properties also affect the ultrasound propagation in bone. The diagnostic potential of ultrasound has not been fully exploited in clinical quantitative ultrasound devices. The aim of this study was to investigate the ability of quantitative ultrasound pulse-echo imaging, conducted over a broad range of frequencies (1 to 5 MHz), to predict the mechanics, composition and microstructure of trabecular bone. Ultrasound reflection and backscatter parameters correlated significantly with the ultimate strength of the trabecular bone and the bone volume fraction (r=0.76-0.90, n=20, p<0.01). Ultrasound backscatter associated significantly (independently of bone structure or mineral content) with the collagen content of the bone matrix (r=0.75, r(adjusted)=0.66, p<0.01). Interestingly, the applied ultrasound frequency seemed to relate the sensitivity of ultrasound backscatter to different properties of trabecular bone. At frequencies ranging from 1 to 3.5 MHz, the ultrasound backscatter associated significantly with the tissue mechanical and structural parameters. At 5MHz, the composition of the bone matrix was a more significant determinant of the measured backscatter. This study provides useful information for optimizing the use of pulse-echo measurements, and thereby further emphasizes the diagnostic potential of the ultrasound backscatter measurements of trabecular bone.