Quantitative ultrasound radiomics guided adaptive neoadjuvant chemotherapy in breast cancer: early results from a randomized feasibility study.

Background: In patients with locally advanced breast cancer (LABC) receiving neoadjuvant chemotherapy (NAC), quantitative ultrasound (QUS) radiomics can predict final responses early within 4 of 16-18 weeks of treatment. The current study was planned to study the feasibility of a QUS-radiomics model-guided adaptive chemotherapy. Methods: The phase 2 open-label randomized controlled trial included patients with LABC planned for NAC. Patients were randomly allocated in 1:1 ratio to a standard arm or experimental arm stratified by hormonal receptor status. All patients were planned for standard anthracycline and taxane-based NAC as decided by their medical oncologist. Patients underwent QUS imaging using a clinical ultrasound device before the initiation of NAC and after the 1st and 4th weeks of treatment. A support vector machine-based radiomics model developed from an earlier cohort of patients was used to predict treatment response at the 4th week of NAC. In the standard arm, patients continued to receive planned chemotherapy with the treating oncologists blinded to results. In the experimental arm, the QUS-based prediction was conveyed to the responsible oncologist, and any changes to the planned chemotherapy for predicted non-responders were made by the responsible oncologist. All patients underwent surgery following NAC, and the final response was evaluated based on histopathological examination. Results: Between June 2018 and July 2021, 60 patients were accrued in the study arm, with 28 patients in each arm available for final analysis. In patients without a change in chemotherapy regimen (53 of 56 patients total), the QUS-radiomics model at week 4 of NAC that was used demonstrated an accuracy of 97%, respectively, in predicting the final treatment response. Seven patients were predicted to be non-responders (observational arm (n=2), experimental arm (n=5)). Three of 5 non-responders in the experimental arm had chemotherapy regimens adapted with an early initiation of taxane therapy or chemotherapy intensification, or early surgery and ended up as responders on final evaluation. Conclusion: The study demonstrates the feasibility of QUS-radiomics adapted guided NAC for patients with breast cancer. The ability of a QUS-based model in the early prediction of treatment response was prospectively validated in the current study. Clinical trial registration: clinicaltrials.gov, ID NCT04050228.

New point-of-care calcaneal ultrasound densitometer (Osteosys BeeTLE) compared to standard dual-energy X-ray absorptiometry (DXA).

Dual-energy X-ray absorptiometry (DXA) represents the gold standard for measuring bone mineral density (BMD). However, its size and bulkiness limit its use in mass screening. Portable and easily accessible instruments are more suitable for this purpose. We conducted a study to assess the repeatability, sensitivity, accuracy, and validation of a new ultrasound densitometer for the calcaneus (OsteoSys BeeTLe) compared to standard DXA. BMD (g/cm2) was measured at the femoral and lumbar spine levels using DXA (Discovery Acclaim (Hologic, Waltham, MA, USA) or Lunar Prodigy (GE Healthcare, Madison, WI, USA) devices). Bone Quality Index (BQI, a dimensionless measure of bone quality derived from measures of SOS [Speed Of Sound] and BUA [broadband ultrasound attenuation]) was measured with OsteoSys BeeTLe. The Bland-Altman test and simple linear regression were used to evaluate the association between values measured with the two instruments. Additionally, the ability of the T-score calculated with BeeTLe to identify patients with previous osteoporotic fractures was tested using ROC curves. A total of 201 patients (94.5% females) with a mean age of 62.1 ± 10.2 were included in the study. The BeeTLe instrument showed a coefficient of variation (CV, in 75 repeated measurements) of 1.21%, which was not statistically different from the CV of DXA (1.20%). We found a significant association between BQI and BMD at the femoral neck (r2 = 0.500, p < 0.0001), total femur (r2 = 0.545, p < 0.0001), and lumbar spine (r2 = 0.455, p < 0.0001). T-scores bias were 0.215 (SD 0.876), 0.021 (SD 0.889) and 0.523 (SD 0.092), for femoral neck, total hip and lumbar spine respectively. AUC for discriminating fracture and non-fractured patients were not significantly different with OsteoSys BeeTLe and standard DXA. In this preliminary study, BeeTLe, a new point-of-care ultrasound densitometer, demonstrated good repeatability and performance similar to DXA. Therefore, its use can be proposed in screening for osteoporosis.

Osteopenia and Osteoporosis Screening Detection: Calcaneal Quantitative Ultrasound with and without Calibration Factor Comparison to Gold Standard Dual X-ray Absorptiometry.

BACKGROUND: osteoporosis is a worldwide major health problem that normally diagnosed in advanced stages. So, an early detection at preclinical stage is now an interesting issue. A key factor to early diagnosis the disease is the used of noninvasive bone densitometry. Dual energy x-ray absorptiometry (DXA) is the gold standard techniques for the proposed. However, the high cost, non-widely available and exposed to ionizing radiation are still a drawback of the machine. Therefore, a cheaper, smaller and non-ionizing device such quantitative ultrasound (QUS) is now a favor alternative method, but the possibility of used QUS measurement instead of DXA is still limited due to their uncertainties. So, the aim of our study was to calibrated the QUS with the DXA to allowing the possible to establish a calibration factor (CF) to improve the measured value closer to the standard method. METHODOLOGY: 135 healthy men and women aged 30-88 years were recruited for lumbar spine/femoral neck DXA and calcaneal QUS scanning. The Pearson's correlation between T- and Z-score from the two systems were studied. Moreover, the sensitivity, specificity and percentage of diagnosed accuracy for both with and without CF were calculated. RESULTS: The significant correlation between the two systems showed a positive trajectory in highly correlation (r = 0.784-0.899). Analyses showed a higher sensitivity, specificity and reduced the misdiagnosed rates when applied the CF in QUS values. CONCLUSIONS: QUS results showed a significantly correlated with DXA results for both lumbar spine and femoral neck sites with some percentage differences. These differences can be reduced by applied an individual specific machine CF to improve a QUS results. As identification of high risk of osteopenia and osteoporosis to reduce the demand of DXA propose, using a QUS alternative method can be a reliable that provide a cheaper and lack of ionizing radiation.

In vivo validation of an in situ calibration bead as a reference for backscatter coefficient calculation.

Objectives: The study aims to assess the capability of Quantitative Ultrasound (QUS) based on the backscatter coefficient (BSC) for classifying disease states, such as breast cancer response to neoadjuvant chemotherapy and quantifying fatty liver disease. We evaluate the effectiveness of an in situ titanium (Ti) bead as a reference target in calibrating the system and mitigating attenuation and transmission loss effects on BSC estimation. Methods: Traditional BSC estimation methods require external references for calibration, which do not account for ultrasound attenuation or transmission losses through tissues. To address this issue, we use an in situ titanium (Ti) bead as a reference target, because it can be used to calibrate the system and mitigate the attenuation and transmission loss effects on estimation of the BSC. The capabilities of the in situ calibration approach were assessed by quantifying consistency of BSC estimates from rabbit mammary tumors (N=21). Specifically, mammary tumors were grown in rabbits and when a tumor reached 1 cm or greater in size, a 2-mm Ti bead was implanted into the tumor as a radiological marker and a calibration source for ultrasound. Three days later, the tumors were scanned with a L-14/5 38 array transducer connected to a SonixOne scanner with and without a slab of pork belly placed on top of the tumors. The pork belly acted as an additional source of attenuation and transmission loss. QUS parameters, specifically effective scatterer diameter (ESD) and effective acoustic concentration (EAC), were calculated using calibration spectra from both an external reference phantom and the Ti bead. Results: For ESD estimation, the 95% confidence interval between measurements with and without the pork belly layer was (6.0,27.4) using the in situ bead and (114, 135.1) with the external reference phantom. For EAC estimation, the 95% confidence interval were (-8.1, 0.5) for the bead and (-41.5, -32.2) for the phantom. These results indicate that the in situ bead method shows reduced bias in QUS estimates due to intervening tissue losses. Conclusions: The use of an in situ Ti bead as a radiological marker not only serves its traditional role but also effectively acts as a calibration target for QUS methods. This approach accounts for attenuation and transmission losses in tissue, resulting in more accurate QUS estimates and offering a promising method for enhanced disease state classification in clinical settings.

Review of Envelope Statistics Models for Quantitative Ultrasound Imaging and Tissue Characterization.

The homodyned K-distribution and the K-distribution, viewed as a special case, as well as the Rayleigh and the Rice distributions, viewed as limit cases, are discussed in the context of quantitative ultrasound (QUS) imaging. The Nakagami distribution is presented as an approximation of the homodyned K-distribution. The main assumptions made are (1) the absence of log-compression or application of nonlinear filtering on the echo envelope of the radiofrequency signal and (2) the randomness and independence of the diffuse scatterers. We explain why other available models are less amenable to a physical interpretation of their parameters. We also present the main methods for the estimation of the statistical parameters of these distributions. We explain why we advocate the methods based on the X-statistics for the Rice and the Nakagami distributions and the K-distribution. The limitations of the proposed models are presented. Several new results are included in the discussion sections, with proofs in the appendix.

Pulse-Echo Technique to Compensate for Laminate Membrane Transmission Loss in Phantom-Based Ultrasonic Attenuation Coefficient Measurements.

OBJECTIVES: Accurately measuring the attenuation coefficient (AC) of reference phantoms is critical in clinical applications of quantitative ultrasound. Phantom AC measurement requires proper compensation of membrane transmission loss. Conventional methods require separate membrane samples to obtain membrane transmission loss. Unfortunately, separate membrane samples are often unavailable. A pulse-echo approach is proposed herein to compensate for membrane transmission loss without requiring separate membrane samples. METHODS: The proposed method consists of the following steps. First, the insertion loss, caused by phantom attenuation and membrane transmission loss, is measured. Second, the membrane reflection coefficient is measured. Third, the unknown acoustic parameters of the membrane and phantom material are estimated by fitting theoretical reflection coefficient to the measured one. Finally, the fitted parameters are used to estimate membrane transmission loss and phantom AC. The proposed method was validated through k-Wave simulations and phantom experiments. Experimental AC measurements were repeated on 5 distinct phantoms by 2 operators to assess the repeatability and reproducibility of the proposed method. Five transducers were used to cover a broad bandwidth (0.7-16 MHz). RESULTS: The acquired AC in the simulations had a maximum error of 0.06 dB/cm-MHz for simulated phantom AC values ranging from 0.5 to 1 dB/cm-MHz. The acquired AC in the experiments had a maximum error of 0.045 dB/cm-MHz for phantom AC values ranging from 0.28 to 1.48 dB/cm-MHz. Good repeatability and cross-operator reproducibility were observed with a mean coefficient of variation below 0.054. CONCLUSION: The proposed method simplifies phantom AC measurement while providing satisfactory accuracy and precision.

Implementation of Non-Invasive Quantitative Ultrasound in Clinical Cancer Imaging.

Quantitative ultrasound (QUS) is a non-invasive novel technique that allows treatment response monitoring. Studies have shown that QUS backscatter variables strongly correlate with changes observed microscopically. Increases in cell death result in significant alterations in ultrasound backscatter parameters. In particular, the parameters related to scatterer size and scatterer concentration tend to increase in relation to cell death. The use of QUS in monitoring tumor response has been discussed in several preclinical and clinical studies. Most of the preclinical studies have utilized QUS for evaluating cell death response by differentiating between viable cells and dead cells. In addition, clinical studies have incorporated QUS mostly for tissue characterization, including classifying benign versus malignant breast lesions, as well as responder versus non-responder patients. In this review, we highlight some of the important findings of previous preclinical and clinical studies and expand the applicability and therapeutic benefits of QUS in clinical settings. We summarized some recent clinical research advances in ultrasound-based radiomics analysis for monitoring and predicting treatment response and characterizing benign and malignant breast lesions. We also discuss current challenges, limitations, and future prospects of QUS-radiomics.

Trabecular bone score and phalangeal quantitative ultrasound are associated with muscle strength and fracture risk in hemodialysis patients.

There is growing interest in the relationship between chronic kidney disease (CKD) and fragility fracture risk. Bone mineral density (BMD) is a major determinant of bone strength, although its role as a predictor of fracture in advanced CKD and hemodialysis is still under debate. We aimed to further investigate surrogates of bone quality and their associations with muscle strength and fracture risk in hemodialysis. Multiple clinical risk factors for fracture and an estimated 10-year probability of fracture, BMD at lumbar spine and femur, trabecular bone score (TBS), X-ray vertebral morphometry, phalangeal bone quantitative ultrasonography (QUS), tibial pulse-echo ultrasonography (PEUS), and handgrip strength were evaluated in a setting of hemodialysis patients in treatment with acetate-free biofiltration (AFB) or bicarbonate hemodialysis. The bone ultrasound measurements, both at phalangeal and tibial sites, were significantly associated with lumbar and femoral DXA values. Handgrip strength was significantly associated with the 10-year probability of fracture (r = -0.57, p < 0.001 for major fractures and r = -0.53, p < 0.001 for hip fracture, respectively), with femur neck, total femur, and L1-L4 BMD values (r = 0.47, p = 0.04; r = 0.48, p = 0.02; r = 0.58, p = 0.007, respectively), with TBS at the lumbar spine (r = 0.71, p < 0.001) and with the phalangeal QUS measure of AD-SoS (r = 0.369, p = 0.023). In the hemodialysis group, 10 participants (24.3%) reported at least one morphometric vertebral fracture (Vfx); conversely, only six participants (15%) showed Vfx in the control group. In the hemodialysis group, participants with Vfx compared with participants without Vfx reported significantly different TBS, bone transmission time (BTT), cortical thickness, and handgrip strength (p < 0.05). At multiple regression analysis, by identifying as dependent variable the 10-year fracture risk for major fracture, after correcting for age, BMI, time since dialysis, AD-SoS, cortical bone thickness, and handgrip strength, only BTT (ß = -15.21, SE = 5.91, p = 0.02) and TBS (ß = -54.69, SE = 21.88, p = 0.02) turned out as independently associated with fracture risk. In conclusion, hemodialysis patients showed a higher fracture risk and lower surrogate indices of bone strength as TBS and QUS parameters. In this cohort of patients, handgrip strength measurements appeared to be a useful instrument to identify high-fracture-risk subjects.

Dietary Saturated Fat and Bone Health in Young Adults: The Young Finns Cohort.

Previous studies suggest that saturated fat (SFA) intake may negatively impact on bone. However, few human studies on the topic exist. Women and men aged 31-46 years from the Cardiovascular Risk in Young Finns study attended the peripheral quantitative computed tomography and ultrasound bone measurements in 2008 (n = 1884-1953, ~ 56% women). In addition, fracture diagnoses in 1980-2018 were searched for the national health care registers and 431 participants had at least one fracture. Food consumption was gathered with the 48-h dietary recall interviews and food frequency questionnaire in 1980-2007. In the present study, radial, tibial, and calcaneal bone traits, and fractures were examined relative to the long-term intake of SFA. No consistent associations were seen between bone outcomes and SFA intake that would have replicated in both women and men. The only evidence for differential distributions was seen in cortical density and cortical-to-total area ratio at the radial shaft, and speed of sound at the calcaneus, which were 0.1-0.4% higher in women in the lowest tertile of SFA intake compared with the highest tertile. In addition, among men, the odds ratio (OR) of fractures was greater in the second (OR 1.86, 95% confidence interval (CI) 1.03-3.33) and third tertile of SFA intake (OR 2.45, 95% CI 1.38-4.36) compared with the lowest tertile, independently of many risk factors of osteoporosis. In this observational study, we found no robust evidence of the associations of dietary long-term SFA intake with bone outcomes. Therefore, additional studies are needed to confirm the association of dietary SFA with bone health in humans.

Relationships between QUS and HR-pQCT, DXA, and bone turnover markers.

INTRODUCTION: Relationship of quantitative ultrasound (QUS) with high-resolution peripheral quantitative computed tomography (HR-pQCT), dual-energy X-ray absorptiometry (DXA), and bone-related biochemical markers was analyzed. MATERIALS AND METHODS: The subjects were 480 individuals. Speed of sound (SOS) was measured by calcaneal QUS. Volumetric bone mineral density (vBMD) and microarchitecture of trabecular and cortical bone in the distal radius and tibia were assessed by HR-pQCT. Areal bone mineral density (aBMD) in the lumbar spine and proximal femur were measured by DXA. TRACP-5b, P1NP, 25 (OH) vitamin D, and pentosidine were evaluated by biochemical tests. The correlation of each parameter was analyzed for all subjects and by sex and age group. RESULTS: QUS was moderately correlated with Tb.vBMD and Tb.BV/TV in the radius and tibia. No correlation was seen with Ct.vBMD or cortical porosity (Ct.Po). Although a correlation was seen with cortical thickness (Ct.Th) in the tibia in all subjects, no correlation was seen in women aged ≥ 60 years. QUS showed moderate correlations with aBMD in the proximal femur. Although moderate correlation was seen with aBMD in the lumbar spine in all subjects, no correlation was seen in subjects aged ≥ 60 years. No significant correlations were seen between QUS and biochemical markers. CONCLUSIONS: Moderate correlations were seen between QUS and Tb.vBMD and microarchitecture in the radius and tibia and aBMD of the proximal femur. On the other hand, practically no correlations were seen with Ct.vBMD or Ct.Po and the bone-related biochemical markers. Only in middle age, moderate correlations were seen with Ct.Th in the tibia and with aBMD of the lumbar spine.

To study the awareness of osteoporosis in postmenopausal Indian women in a Northeast part of India: An evaluation of the Osteoporosis Health Belief Scale.

AIM AND OBJECTIVE: Our study's objective is to determine the level of awareness in postmenopausal women in Guwahati, Northeast part of India, using the Osteoporosis Health Belief Scale (OHBS). SETTINGS AND DESIGN: Osteoporosis is the most common silent health problem in postmenopausal Indian women. An awareness level among this subset of women needs to study. The present study is based on a self-explanatory questionnaire. METHODS: We conducted a self-explanatory questionnaire study on 2000 postmenopausal women in Guwahati, North East region of India. The bone mineral density (BMD) was measured using calcaneum Quantitative ultrasound (QUS) to assess BMD. Baseline characteristics were noted and analyzed. RESULTS: The awareness level was noted only in757 (37.85%). Women with education level 12th standard and above have some awareness regarding osteoporosis. CONCLUSIONS: Based on the present study, we can conclude that there is a lack of awareness in postmenopausal women regarding osteoporosis in India's North-East region. This subset of women is unaware of the condition that can leads to fragility fracture if not address in time. The study emphasizes that health care professionals should conduct frequent awareness programs in the community to prevent this silent disease, and morbidities so arise from osteoporosis can be minimized.

The quantitative ultrasound method for assessing low bone mass in women with anorexia nervosa.

This study investigated the potential role of quantitative ultrasound (QUS) to assess low bone mass in anorexia nervosa patients (AN). Bone parameters from QUS and DXA were positively correlated and significantly reduced in AN compared with controls, suggesting that QUS is a pertinent technique to assess low bone mass in these patients. PURPOSE: The aim of this study was to investigate the potential role of an alternative technique, quantitative ultrasound (QUS), to assess low bone mass in patients with anorexia nervosa (AN). METHODS: Two hundred seven young women (134 patients with AN and 73 healthy controls) with ages ranging from 14.4 to 38.4 years participated in this observational cross-sectional study. Bone mass was concomitantly evaluated by DXA to determine areal bone mineral density (aBMD; g/cm2) at hip, lumbar spine, and radius and by QUS to determine broadband ultrasound attenuation (BUA; dB/MHz) at the heel. RESULTS: BUA (66.5 ± 4.6 dB/MHz vs 61.0 ± 5.0 dB/MHz) and aBMD at the hip (0.916 ± 0.013 g/cm2 vs 0.806 ± 0.010 g/cm2), lumbar spine (0.966 ± 0.012 g/cm2 vs 0.886 ± 0.010 g/cm2), and radius (0.545 ± 0.005 g/cm2 vs 0.526 ± 0.04 g/cm2) were significantly decreased (p < 0.01) in patients with AN compared with controls. When patient and control data were pooled, BUA was significantly correlated with aBMD at the hip (r = 0.60, p < 0.001), lumbar spine (r = 0.48, p < 0.001), and radius (r = 0.40, p<0.001). In patients with AN, BUA and aBMD were mainly and positively correlated with weight, lean tissue mass, body mass index (BMI), and minimal BMI life and negatively with the duration of both disease and amenorrhea. Better concordance between the two techniques was obtained when absolute BUA and aBMD values were used according to the WHO T score classification. CONCLUSION: BUA measurement at the heel by QUS appears to be a pertinent nonionizing technique to assess low bone mass in patients with AN.

Development of a QUS Device to Evaluate Deterioration of Cortical Bone: Verification by HR-pQCT and Measurements in Healthy Individuals and Dialysis Patients.

INTRODUCTION: The objectives of this study were to identify what is reflected in cortical speed of sound (cSOS) measured by a cortical quantitative ultrasound (cortical QUS) device we have developed, and to investigate cSOS measurements in healthy individuals and dialysis patients. METHODS: The cSOS and the SOS were measured by cortical QUS and conventional QUS in 20 volunteers, and the correlations between these measurements and areal bone mineral density measured by dual-energy X-ray absorptiometry and bone microstructural parameters on high-resolution peripheral quantitative computed tomography were analyzed. The cSOS and the SOS were measured in 91 young adults (47 men, 44 women), 64 elderly people (30 men, 33 women), and 64 dialysis patients (33 men, 31 women). The period of hemodialysis and intact parathyroid hormoneevels were also investigated in the dialysis patients. RESULTS: cSOS was correlated with cortical tissue mineral density (tibia: r = 0.74, radius: r = 0.72) on high-resolution peripheral quantitative computed tomography, reflecting the degree of minaralization and microporosity of cortical bone. There was no correlation with the thickness of cortical bone, suggesting that it measured the bone quality rather than bone mass. Elderly women had lower cSOS than young adults (3865 ± 74 vs 3971 ± 63 m/s, p < 0.01). Many of dialysis patients showed very low cSOS and it was related to higher intact parathyroid hormone levels (male: ß = -0.67, female: ß = -0.60). CONCLUSIONS: Our cortical QUS device is capable of evaluating the qualitative degradation of cortical bone, which cannot be assessed by conventional QUS, and its use in combination with conventional QUS may provide a better understanding of fracture risk.

Poor Bone Quality in Patients With Amyotrophic Lateral Sclerosis.

Objective: Musculoskeletal functional deterioration in Amyotrophic lateral sclerosis (ALS) is associated with an increase in bone fractures. The purpose of this study was to evaluate the influence of sex, ALS type, on bone quality in patients with ALS compared to healthy controls. The impact on bone health of the clinical status and some metabolic parameters was also analyzed in ALS patients. Methods: A series of 33 voluntary patients with ALS, and 66 healthy individuals matched in sex and age underwent assessment of bone mass quality using quantitative ultrasound (QUS) of the calcaneus. Ultrasonic broadband attenuation (BUA), the speed of sound (SOS), stiffness index and T-score were measured. Bone mineral density (BMD) was estimated using standard equations. Apart from fat and muscle mass percentage determinations, clinical baseline measures in ALS patients included ALSFRS-R score, Barthel index for activities of daily living, pulmonary function measured using FVC, and muscular strength assessed by a modified MRC grading scale. Laboratory tests included serum calcium, 25-HO-cholecalciferol (Vitamin D), alkaline phosphatase (ALP), T4 and TSH. Results: All bone parameters evaluated were statistically significant lower in ALS patients than in healthy controls. ALS females showed significantly lower bone parameters than healthy females. According to the estimated BMD, there were 25 ALS patients (75.8%) and 36 (54.5%) healthy individuals showing an osteoporotic profile (BMD <0.700 g/cm2). Only 16.7% of the ALS females had T-scores indicative of healthy bones. There was no correlation between any of the clinical parameters analyzed and the bone QUS measurements. Vitamin D and TSH levels positively correlated with all the bone parameters. Conclusions: This study confirms that ALS patients, particularly females, exhibited deteriorated bone health as compared to healthy individuals. These structural bone changes were independent of ALS subtype and clinical status. Bone health in ALS patients seems to be related to certain metabolic parameters such as Vitamin D and TSH levels.

Bone strength of the proximal femur in healthy subjects with ossification of the posterior longitudinal ligament.

We compared the bone strength measured via quantitative computed tomography-based finite element method (QCT/FEM) between healthy adults with and without ossification of the posterior longitudinal ligament (OPLL). No statistically significant difference was observed in the bone strength between healthy adults with and without OPLL. Hyperostosis of the posterior longitudinal ligament in OPLL may not be associated with the systemic bone strength. INTRODUCTION: Although patients with OPLL have been reportedly associated with increased level of bone mineral density (BMD) using dual-energy X-ray absorptiometry (DXA), little is known about the bone strength in OPLL subjects. The aim of this study is to investigate the bone strength measured via QCT/FEM in healthy subjects with OPLL using the medical check-up data, including whole-body CT scans. METHODS: We examined 796 participants (529 men and 267 women) who underwent CT scans in a single health center between January 2008 and May 2009. We identified OPLL in whole spine and divided the subjects into two groups: non-OPLL and OPLL groups. We calculated the predicted bone strength (PBS) of the proximal femur using QCT/FEM and examined the bone mineral status of the calcaneus using quantitative ultrasound (QUS). We compared the PBS and the QUS parameters between the non-OPLL and OPLL groups. RESULTS: Seventy-four subjects (9.3%; 57 men and 17 women) were diagnosed with OPLL in the whole spine. The OPLL group was significantly older than the non-OPLL group. No statistically significant difference was observed in the PBS and the QUS parameters between the non-OPLL and OPLL groups in both sexes. Furthermore, no statistically significant difference was noted in the PBS and the QUS parameters between two groups in age- and gender-matched analysis. CONCLUSIONS: Our results suggest that hyperostosis of the posterior longitudinal ligament in OPLL may not be associated with bone strength and bone mineral status at the extremities.

Quantitative ultrasound for monitoring bone status in institutionalized adults with refractory epilepsy and intellectual disability: A 7-year follow-up study.

PURPOSE: Long-term exposure to anti-epileptic drugs has been shown to decrease bone mineral density (BMD). The aim of this 7-year follow-up study was to explore changes in bone status, using quantitative ultrasound (QUS) and Dual-energy X-ray Absorptiometry (DXA) in adults with refractory epilepsy and intellectual disability (ID) residing at a long-term care facility. Both measurements can be challenging to conduct in this population. METHODS: In 2009 and 2016, a total of 126 patients (18-79 years) underwent QUS of the heel and DXA of lumbar spine (LS) and hip (femoral neck (FN) and total hip (TH)). Subgroup analysis was performed for patients with (group A, n = 53) and without (group B, n = 73) bisphosphonate use during follow-up. RESULTS: Overall, weak to moderate correlations between changes in DXA and QUS parameters were found. For group A, correlations varied from r = .31 to .59, whereas correlations did not exceed r = .40 in group B. Patients in group A showed a larger increase or a smaller decrease in BMD for all DXA regions during follow-up (p < .001 for ΔLS and ΔFN BMD, p = .001 for ΔTH BMD). For change in QUS parameters, no significant difference between groups was found. CONCLUSION: In this study we demonstrated the limited use of QUS in the monitoring of bone status in our study population. Although correlations between changes in QUS parameters and axial DXA are positive and mostly significant, QUS only explains little of the variability in DXA values and is inadequate for measuring treatment response in this population.

Relationship between bone turnover markers and the heel stiffness index measured by quantitative ultrasound in post-menopausal Japanese women.

Background: Osteoporosis in women is a serious health problem. The relationships between biochemical markers of bone turnover and bone mineral density (BMD) in women have been reported, but no study has examined relationships between tartrate-resistant acid phosphatase-5b (TRACP-5b) or bone-specific alkaline phosphatase (BAP) and bone mass measured by quantitative ultrasound (QUS) in Japanese post-menopausal women. Aim: To investigate the serum TRACP-5b and BAP levels and to determine their associations with the heel stiffness index measured by QUS in post-menopausal women. Subjects and methods: The subjects were 510 post-menopausal women who were invited to participate in periodic health examinations in 2011-2013 (the Unzen Study). The heel stiffness index (bone mass) was measured by QUS. Serum samples were collected and TRACP-5b and BAP levels were measured. Results: Multiple regression analysis showed that a higher log (TRACP-5b) was correlated with a lower stiffness index (p = 0.014) and log (BAP) was not correlated with stiffness index after adjusting for covariates (p = 0.136). Conclusion: Higher rates of bone resorption are associated with a lower stiffness index in Japanese post-menopausal women. These results may indicate that high bone resorption affects bone mass more than bone formation, resulting in a low bone mass.

Clinical utilities of quantitative ultrasound in osteoporosis associated with inflammatory rheumatic diseases.

Secondary osteoporosis is an important co-morbidity related to inflammatory rheumatic diseases that is attributed to several factors including inflammatory cytokines, inactivity and glucocorticoid treatment. Quantitative ultrasound (QUS) has been utilized in osteoporosis research due to its detectability of bone density as well as bone quality. The current narrative review is to address the potential utilities of QUS in secondary osteoporosis of inflammatory rheumatic diseases, focusing on the clinical aspects of QUS in these diseases, based on the conformity of QUS with dual emission X-ray absorptiometry (DXA), the relationship with disease characteristics, and its capability of fracture prediction. Although limited data demonstrate that QUS had moderate to strong correlation with DXA, and might be useful as a potential imaging tool to screen for osteoporosis, further research is still required for QUS to be utilized effectively for the best outcome in these patients with rheumatic diseases.

Higher step count is associated with greater bone mass and strength in women but not in men.

In this cross-sectional study, peripheral bone traits were examined relative to total daily steps measured with pedometer. Higher number of steps was associated with greater bone values at the calcaneus and tibia in women, but not in men. In women, dose-dependent associations at the radius were congruent with the weight-bearing bones. INTRODUCTION: Habitual physical activity measured as daily steps may contribute to bone density and strength at the calcaneus and other weight-bearing bones. METHODS: Subgroups of 705-837 women and 480-615 men aged 31-46 years from the Cardiovascular Risk in Young Finns Study participated in the present study. Participants were instructed to use pedometer for 1 week, and the total daily steps, divided into tertiles, were evaluated relative to quantitative ultrasound-measured bone traits at the calcaneus and peripheral quantitative computed tomography-measured bone traits at the tibia and radius. Analysis of covariance was used to examine the between-group differences. RESULTS: In women, significant dose-dependent between-group differences were found in the weight-bearing bones and in non-weight-bearing radius. The differences in broadband ultrasound attenuation and speed of sound at the calcaneus were 3.8 and 0.5% greater in women within the highest tertile of daily steps compared to the lowest tertile (p values for trend ≤ 0.04). In tibia, women in the highest tertile (> 8765 steps/day) had on average 1-5.4% greater bone cross-sectional area, bone mineral content (BMC), trabecular density, and bone strength index at the distal site and 1.6-2.7% greater bone areas, BMC and strength strain index (SSI) at the shaft compared to women with less daily steps (p values for trend ≤ 0.02). Similarly, in radius, BMC and BSI at the distal site, and bone cross-sectional areas, BMC and SSI at the shaft were 1.7-3.4% greater in women within the highest tertile of daily steps compared to their peers (p values for trend ≤ 0.04). In men, the differences in calcaneal, tibial, and radial bone traits were mainly non-significant between the tertiles of daily steps. CONCLUSION: Observed significant positive associations between daily steps and various bone traits at the calcaneus, tibia, and radius in women suggest that habitual physical activity may benefit skeletal health in adulthood.

Attempt at standardization of bone quantitative ultrasound in Japan.

Dual X-ray absorptiometry (DXA) is used to diagnose osteoporosis. On the other hand, quantitative ultrasound (QUS) is widely used to assess bone density as part of medical screening as it is relatively inexpensive and easy to perform. Current QUS devices do not share precise ultrasound-related parameters, such as frequency, waveform, beam pattern, transient response, definition of propagation time, definition of degree of attenuation, and precise measurement site, resulting in different measurements across models. The Japan Osteoporosis Society established a QUS Standardization Committee in 2007 to investigate standardization of speed of sound (SOS) and broadband ultrasonic attenuation (BUA) measurements to resolve this issue. The committee came up with a formula to convert SOS and BUA values yielded by each model available in Japan. This has made it possible to convert QUS measurements from different models into standardized values, greatly improving the effectiveness of QUS measurements.