Heel Quantitative Ultrasound Research Articles

Antipsychotic medication use in association with quantitative heel ultrasound (QUS)

PurposeAntipsychotic medication use has been associated with decreased bone mineral density; however, less is known whether antipsychotics affect other parameters of bone health. Therefore, the aim of this study was to investigate the association between antipsychotic medication use and quantitative heel ultrasound (QUS) in a population based sample of men and women. MethodsThirty-one antipsychotic users and 155 non-users matched for age and sex were drawn from the Geelong Osteoporosis Study. QUS was undertaken and included the parameters: Broadband ultrasound attenuation (BUA), speed of sound (SOS) and stiffness index (SI). Current medication use, lifestyle factors, anthropometry and socio-economic status were collected. Generalized Estimation Equation models were conducted to determine associations between antipsychotic medication use and each of the QUS parameters, adjusting for covariates. ResultsAntipsychotic users were less active, consumed less alcohol, were more likely to smoke and take antidepressants; otherwise, the groups were similar. After adjusting for age, sex and weight, antipsychotic users had a 7.7 % lower mean BUA [108.70 (95 % CI 104.26–113.14) vs. 116.42 (95 % CI 115.48–117.37) dB/MHz, p = 0.005] and 7.4 % lower mean SI [89.92 (95 % CI 86.89–92.95) vs. 97.30 (95 % CI 96.48–98.12) %, p < 0.001] compared to non-users. Differences in mean SOS between antipsychotic users and non-users failed to reach statistical significance (p = 0.07). ConclusionAntipsychotic use was associated with lower QUS parameters. The risk of bone deterioration should be considered when antipsychotics are prescribed.

Lipopolysaccharide-binding protein and bone health: data from a population-based sample of men.

The objective of this study was to investigate the association between serum lipopolysaccharide-binding protein (LBP) and potential downstream effects on skeletal density, quality, and turnover in a population-based sample of men. This cross-sectional study utilised data from 1149 men (aged 20-96year) enrolled in the Geelong Osteoporosis Study. Blood samples were obtained and lipopolysaccharide-binding protein (LBP), bone resorption marker, C-telopeptide (CTx), and formation marker, type 1 procollagen amino-terminal-propeptide (P1NP), were measured. Bone mineral density (BMD) was measured using dual-energy X-ray absorptiometry. Stiffness Index (SI), broadband ultrasound attenuation (BUA), and speed of sound (SOS) were derived from quantitative heel ultrasound (QUS). Linear regression models were developed to test associations between log-transformed LBP (ln-LBP), BMD, QUS, and bone turnover, after adjusting for potential covariates. Serum LBP ranged from 1.07-208.53ng/mL (median 16.53ng/mL). Those with higher levels were older, less mobile, and had lower BMD at the mid-forearm, otherwise, groups were similar. Before and after adjustment for age, ln-LBP was associated with lower BMD at the spine, total body, and mid-forearm. Further adjustment for weight attenuated associations at the spine and total body, yet the relationship at the mid-forearm was sustained (β - 0.014 ± 0.004, p = 0.001). SOS and SI were not associated with ln-LBP either before or after adjustment for age; however, weight was identified as an effect modifier in the relationship between ln-LBP and BUA. An association was observed for those weighing greater than 82.7kg (β 3.366 ± 0.929, p < 0.001), after adjustment for potential covariates. Neither bone turnover marker was associated with ln-LBP. Our data do not support a clear association between serum LBP and measures of bone health in this sample of men.

Anticonvulsant use and bone health in a population-based study of men and women: cross-sectional data from the Geelong Osteoporosis Study

BackgroundAnticonvulsant use has been linked to bone deficits in specific patient populations. We studied the association between anticonvulsant use and bone health in a population-based sample of men and women.MethodsData from 926 men (24-73 yr) and 1070 women (21-94 yr) participating in the Geelong Osteoporosis Study were included. Bone mineral density (BMD, g/cm2) of the PA-spine and total hip was measured using dual-energy X-ray absorptiometry (Lunar). Bone quality was determined using quantitative heel ultrasound (QUS). Anthropometry was conducted and socioeconomic status was determined. Medication and lifestyle information was obtained via questionnaire. Linear regression was used to test associations between anticonvulsant use and bone health before and after adjustment for potential confounders.ResultsSeventeen (1.8%) men and 20 (1.9%) women reported anticonvulsant use. In men, anticonvulsant users had 9.1% lower adjusted mean BMD at the spine and hip compared to non-users. Body mass index was an effect modifier at the spine. Anticonvulsant users also had 1.8% lower speed of sound (SOS), 10.6% lower broadband ultrasound attenuation (BUA) and 13.7% lower stiffness index (SI) compared to non-users. In women, BMD tended to be lower at the hip compared to non-users as with the bone quality measure, BUA. No significant associations were observed at the spine or the other bone quality measures, SOS and SI.ConclusionOur data suggest that bone quantity and quality, assessed using BMD and QUS, are lower for men and possibly women who use anticonvulsants. While further exploration into potential mechanisms is needed, our findings suggest that monitoring bone health among users of anticonvulsants is warranted.

Quantitative Ultrasound of the Heel in Women With Knee Osteoarthritis

The prevalence of multiple falls is higher in older women, and knee pain is associated with multiple falls in women; thus, it is important to detect individuals at risk of fractures among women with knee osteoarthritis. We aimed to clarify the association between knee osteoarthritis and the quantitative ultrasound (QUS) parameter, and investigate the clinical relevance of the QUS parameter with osteoarthritis-related characteristics in women with knee osteoarthritis. This was a cross-sectional study. We recruited 101 women with knee osteoarthritis at a local orthopedic hospital and 102 healthy individuals from the community. Heel QUS measurements were performed using the QUS device, measuring the stiffness index. We also assessed knee pain, quadriceps strength, and physical activity in women with knee osteoarthritis. We fitted a multiple regression model to estimate the association between knee osteoarthritis and the stiffness index. We also fitted 3 multiple regression models to investigate the clinical relevance of the QUS parameter with osteoarthritis-related characteristics in women with knee osteoarthritis. Compared with the control group, individuals with grade 2 osteoarthritis did not demonstrate a significant difference in stiffness index (p = 0.68); however, those with grade 3 osteoarthritis (p < 0.001) and 4 (p < 0.001) showed a lower stiffness index than that of the control group. Additionally, although the QUS parameter did not show an association with knee pain score (p = 0.70) or quadriceps strength (p = 0.11), we found a significant association between the QUS parameter and physical activity (p = 0.003). Our results demonstrate that women with moderate or severe knee osteoarthritis showed lower QUS parameters compared to healthy women, and the QUS parameter was associated with physical activity in women with knee osteoarthritis.

Vitamin K deficiency, evaluated with higher serum ucOC, was correlated with poor bone status in women

BackgroundAn increase in serum undercarboxylated osteocalcin concentrations suggests vitamin K deficiency. Clinical intervention studies suggested that the vitamin K supplementation might contribute to preventing bone loss in postmenopausal women. Evidence on the relationship between serum undercarboxylated osteocalcin (ucOC) levels and bone parameters of quantitative ultrasound (QUS) is limited. We examined the correlation between serum ucOC concentrations and bone status as measured by QUS among middle-aged and older Japanese men and women.MethodsThe subjects were community-dwelling men (n = 358) and women (n = 503) aged ≥ 40 years in Japan. Heel QUS parameters, including the stiffness index, speed of sound, and broadband ultrasound attenuation, were measured. Serum ucOC concentrations were measured by electrochemiluminescence immunoassay. Grip strength was measured in the dominant hand. Information on alcohol drinking, current smoking, exercise, and menopause in women was collected.ResultsSerum ucOC concentrations were significantly associated with age in both sexes. Serum ucOC concentrations in men were higher at ≥ 80 years than those in the age groups of 40–49, 50–59, and 60–69 years. Serum ucOC concentrations in women were higher in the age groups of 50–59 and 60–69 years than those at 40–49 years. Partial correlation analysis adjusting for covariates (age, body mass index, grip strength, alcohol drinking, current smoking, and exercise in men; age, body mass index, grip strength, alcohol drinking, current smoking, exercise, and menopause in women) showed that serum ucOC concentrations were negatively significantly correlated with all QUS parameters in women. Serum ucOC concentrations were not correlated with them in men.ConclusionsVitamin K deficiency, evaluated with higher serum ucOC, was correlated with poor bone status in women.

A study of the incidence of hip fractures in post-menopausal patients undergoing hemodialysis using quantitative ultrasound, digital image processing and the fracture risk assessment tool

To investigate whether a combination of readily available osteoporosis screening systems, instead of dual energy X-ray absorptiometry (DXA), can aid in the identification of characteristic features of hip fracture in post-menopausal patients undergoing hemodialysis. Forty patients (58-90 years old) who had undergone quantitative ultrasound (QUS) on more than one occasion were included. Heel QUS (conducted yearly for 3 years), digital image processing (DIP), and the fracture risk assessment tool (FRAXR) were used to evaluate bone fragility. The latter two assessments (DIP and FRAXR) were conducted on 25 and 26 of the 40 patients mentioned above respectively, for this study. Hip fractures were identified in five patients. The mean values of broadband ultrasound attenuation (BUA) and speed of sound (SOS) in patients with hip fractures were 80±7 dB/MHz and 1,491±14 m/s, respectively, while the recorded values in patients without fractures were 88±9 dB/MHz and 1,506±22 m/s, respectively. The maximum value of BUA and SOS in patients with hip fractures were 91 dB/MHz and 1,510 m/s, respectively. These values were similar to the mean values in patients without fractures. The DIP (YAM) was 55-67% in four patients with fractures, compared to 44 - 91% in 25 examined patients without fractures. Moreover, in four patients with fractures, the FRAXR score was 12 - 55% for major osteoporotic fracture (MOF) and 3.3 - 9.3% for hip fracture (HF), compared to 4.4 - 33% for MOF and 0.3 -18% for HF in 26 examined patients without fractures. The results of these three methods were not statistically significant between patients with and without fractures. The combination of the three screening systems was not superior diagnostic method for hip fractures in post-menopausal patients, compared to DXA. Heel QUS and FRAXR (MOF, HF), both of which do not include bone mineral content (BMC) and DIP (peripheral cortical bone), which accounts for BMC, were used to evaluate bone fragility. In patients undergoing hemodialysis, the clinical importance of measuring DXA is growing, but it is necessary to estimate not only bone mass, but also bone quality. New modalities for the evaluation of bone quality are required in the future.

Bone mineral density as a dose-response predictor for osteoporosis: a propensity score analysis of longitudinal incident study (KCIS no. 39).

Osteoporosis is a global disease burden for aging society. The role of quantitative ultrasound (QUS) in the prediction for osteoporosis in a dose-response manner is hardly addressed. We aimed to show the dose-response of QUS measurement in the prediction for osteoporosis by a community-based study. A prospective cohort study. Participants were recruited between 2000 and 2004. Demographic data and heel QUS measurement were collected at baseline. Diagnosis of osteoporosis was ascertained by the follow-up of this cohort over time. In order to reduce the imbalance of baseline characteristics in the observational study, we applied propensity score by using proportional odds regression analysis to match the quintiles of QUS T-score. A total of 44 957 subjects composed of 17 678 men (39.3%) and 27 279 women (69.7%) were recruited. After adjustments for propensity score, an increase in one unit of QUB T-score led to 7% reduction in the risk for osteoporosis [adjusted odds ratio (OR) = 0.93, 95% confidence interval (CI): 0.89-0.96, P < 0.0001]. Higher quintile of QUS T-score yielded a lower risk of osteoporosis with a gradient relationship [OR: 0.82 (95%CI: 0.72-0.92); OR: 0.81 (95%CI: 0.71-0.91); OR: 0.77 (95%CI: 0.68-0.87) and OR: 0.76 (95%CI: 0.67-0.86)] from the second to highest quintile opposed to first quintile (P < 0.0001). The cumulative incidence of osteoporosis was higher in the lower quintile during follow-up (log-rank test, P < 0.001). QUS is an independent predictor for osteoporosis in a dose-response manner using a large population-based cohort. Due to the lower cost and portability of QUS measurement, the pre-screening for osteoporosis by QUS can be considered in the area with limited resources can be a feasible and alternative method.

RANKL/RANK/OPG Polymorphisms and Heel Quantitative Ultrasound in Young Adults.

The receptor activator of the nuclear factor-kappa B ligand (RANKL), the receptor activator of nuclear factor-kappa B (RANK), and the osteoprotegerin (OPG) signaling pathway play an important role in the regulation of bone remodeling and osteoclast differentiation. Quantitative ultrasound (QUS) is a relatively recent and noninvasive method providing structural information on microstructure, bone elasticity, and connectivity. However, in contrast to bone mineral density measurements, the possible association of the RANKL/RANK/OPG pathway with heel QUS has not been analyzed. The aim of this study was to assess, for the first time, the contribution of the RANKL/RANK/OPG pathway genes in the genetic background of heel QUS parameters. Ten single-nucleotide polymorphisms (SNPs) of RANKL (rs9594759, rs12585014, rs7988338, rs2148073), RANK (rs1805034, rs12458117, rs3018362), and OPG (rs4355801, rs3102735, rs2073618) were selected as genetic markers and genotyped using Open Array technology in 575 self-reported Caucasian individuals aged 18-25. Bone mass in the right calcaneus was estimated with QUS to obtain the broadband ultrasound attenuation (BUA) measurement (dB/MHz). Linear regression analyses were performed to test the possible association between the SNPs and BUA. Linear regression analysis of all the tested SNPs revealed no significant association with the BUA parameter after adjusting for age, gender, weight, height, physical activity, and calcium intake. The lowest p-value was observed for the rs9594759 RANKL polymorphism and heel QUS (p = .06; b* = -.075, 95% CI [-0.960, 0.028]). Our results suggest that the polymorphism of the RANKL, RANK, and OPG genes does not make a significant genetic contribution to heel ultrasound measurements in a population of young Caucasian adults. Further studies replicating the results in independent populations are needed to support these initial findings.

Serum uric acid is associated with quantitative ultrasound parameters in men: data from the Camargo cohort.

This study analyzes the association between serum uric acid levels and heel quantitative ultrasound (QUS) parameters in men aged 50 or more from the Camargo cohort. We found that higher serum uric acid levels are positively associated with all QUS measurements, suggesting a better bone quality in men with elevated serum uric acid values. Higher serum uric acid concentrations have been associated with higher bone mineral density and lower prevalence of fractures. However, there are no studies that have assessed the bone quality properties in Caucasians. Therefore, we have analyzed the association between quantitative ultrasound (QUS) and serum uric acid levels in adult men from a population-based cohort. A total of 868 men older than 50 were recruited from a larger cohort (Camargo Cohort) after excluding those with any known condition or drug treatment with a possible influence on bone metabolism, or those with a previous diagnosis of gout or taking hipouricemic agents. Bone turnover markers (PINP and CTX), 25OH-vitamin D and PTH levels were measured by electrochemiluminiscence. BMD was determined by DXA, and heel QUS with a gel-coupled device. Lumbar, femoral neck and total hip BMD was significantly higher in men with higher serum uric acid levels. QUS parameters were also significantly higher in men with high uric acid levels than those with lower values, and increased continuously across quartiles after adjustment for confounding variables. In multiple regression analysis, serum uric acid was significantly associated with all QUS parameters. Finally, men with serum acid levels above median showed higher values in all the QUS parameters than men with lower values. Higher serum uric acid levels in men older than 50 years are positively associated with QUS parameters. These data might suggest a better bone quality in men with elevated serum uric acid values.

Alcohol consumption and body composition in a population-based sample of elderly Australian men

Alcohol is calorie dense, and impacts activity, appetite and lipid processing. The aim of this study was to therefore investigate the association between alcohol consumption and components of body composition including bone, fat and lean tissue. Participants were recruited from a randomly selected, population-based sample of 534 men aged 65 years and older enrolled in the Geelong Osteoporosis Study. Alcohol intake was ascertained using a food frequency questionnaire and the sample categorised as non-drinkers or alcohol users who consumed ≤2, 3-4 or ≥5 standard drinks on a usual drinking day. Bone mineral density (BMD), lean body mass and body fat mass were measured using dual energy X-ray absorptiometry; overall adiposity (%body fat), central adiposity (%truncal fat) and body mass index (BMI) were calculated. Bone quality was determined by quantitative heel ultrasound (QUS). There were 90 current non-drinkers (16.9 %), 266 (49.8 %) consumed 1-2 drinks/day, 104 (19.5 %) 3-4 drinks/day and 74 (13.8 %) ≥5 drinks/day. Those consuming ≥5 drinks/day had greater BMI (+4.8 %), fat mass index (+20.1 %), waist circumference (+5.0 %), %body fat (+15.2 %) and proportion of trunk fat (+5.3 %) and lower lean mass (-5.0 %) than non-drinkers after adjustment for demographic and lifestyle factors. Furthermore, they were more likely to be obese than non-drinkers according to criteria based on BMI (OR = 2.83, 95 %CI 1.10-7.29) or waist circumference (OR = 3.36, 95 %CI 1.32-8.54). There was an inverse relationship between alcohol consumption and QUS parameters and BMD at the mid forearm site; no differences were detected for BMD at other skeletal sites. Higher alcohol intake was associated with greater total and central adiposity and reduced bone quality.

Quantitative Heel Ultrasound (QUS) measures of bone quality in association with mood and anxiety disorders

BackgroundThe common mental disorders are potential risk factors for low bone mass as a result of disease and/or medication-related processes. Quantitative heel ultrasound (QUS) is a portable and relatively cheap screening tool for determining fracture risk. Thus, we investigated the association between QUS parameters, mood and anxiety disorders in a population-based sample of 745 men and 897 women. MethodsUsing a clinical interview (SCID-I/NP), mood and anxiety disorders were identified. Bone quality was established using QUS and included the following parameters: Broadband Ultrasound Attenuation (BUA), Speed of Sound (SOS) and Stiffness Index (SI). Anthropometry, socio-economic status (SES), medication use and lifestyle factors were determined. ResultsIn men, mood and anxiety disorders were associated with lower age–weight- and smoking-adjusted SOS, BUA and SI. In women, age was an effect modifier. Among younger women (≤40yr), mood disorders were associated with lower age–weight- and smoking-adjusted SOS and SI but not BUA. No differences were detected in older women or women with anxiety disorders. These patterns persisted after adjustment for activity, alcohol, calcium intake, SES and medications. LimitationsCross-sectional study design, and possible residual or unrecognised confounding. ConclusionOur data suggest that bone quality, as measured by QUS, is reduced among men and younger women with a history of mood disorders. Furthermore, an inverse association between anxiety disorders and bone quality was evident for men. Thus, QUS may be a useful screening tool for determining fracture risk within these populations.

Influence of Inflammatory Polyarthritis on Quantitative Heel Ultrasound Measurements

BackgroundThere are few data concerning the impact of inflammatory polyarthritis (IP) on quantitative heel ultrasound (QUS) measurements. The aims of this analysis were i) to determine the influence of IP on QUS measurements at the heel and, ii) among those with IP to determine the influence of disease related factors on these measurements.MethodsMen and women aged 16 years and over with recent onset IP were recruited to the Norfolk Arthritis Register (NOAR). Individuals with an onset of joint symptoms between 1989 and 1999 were included in this analysis. At the baseline visit subjects underwent a standardised interview and clinical examination with blood taken for rheumatoid factor. A population-based prospective study of chronic disease (EPIC-Norfolk) independently recruited men and women aged 40 to 79 years from the same geographic area between 1993 and 1997. At a follow up assessment between 1998 and 2000 subjects in EPIC-Norfolk were invited to have quantitative ultrasound measurements of the heel (CUBA-Clinical) performed. We compared speed of sound (SOS) and broadband ultrasound attenuation (BUA), in those subjects recruited to NOAR who had ultrasound measurements performed (as part of EPIC-Norfolk) subsequent to the onset of joint symptoms with a group of age and sex matched non-IP controls who had participated in EPIC-Norfolk. Fixed effect linear regression was used to explore the influence of IP on the heel ultrasound parameters (SOS and BUA) so the association could be quantified as the mean difference in BUA and SOS between cases and controls. In those with IP, linear regression was used to examine the association between these parameters and disease related factors.Results139 men and women with IP and 278 controls (mean age 63.2 years) were studied. Among those with IP, mean BUA was 76.3 dB/MHz and SOS 1621.8 m/s. SOS was lower among those with IP than the controls (difference = −10.0; 95% confidence interval (CI) –17.4, -2.6) though BUA was similar (difference = −1.2; 95% CI −4.5, +2.1). The difference in SOS persisted after adjusting for body mass index and steroid use. Among those with IP, disease activity as determined by the number of swollen joints at baseline, was associated with a lower SOS. In addition SOS was lower in the subgroup that satisfied the 1987 ACR criteria. By contrast, disease duration, steroid use and HAQ score were not associated with either BUA or SOS.ConclusionsIn this general population derived cohort of individuals with inflammatory polyarthritis there is evidence from ultrasound of a potentially adverse effect on the skeleton. The effect appears more marked in those with active disease.

Discriminative Ability of Heel Quantitative Ultrasound in Postmenopausal Women with Prevalent Vertebral Fractures: Application of Optimal Threshold Cutoff Values Using Classification and Regression Tree Models

Quantitative ultrasound (QUS) of the heel has been proposed as a screening tool to evaluate the bone status and risk of osteoporotic fragility fractures. The aim of this study was to define threshold values that would maximize the predictive ability of QUS to discriminate subjects with vertebral fractures using the classification and regression trees (CART) models. A cross-sectional analysis was made of a cohort of 1,132 postmenopausal women with a mean age of 58years. A total of 205 women (18.1%) presented with a history of vertebral fracture. For all patients, a questionnaire of osteoporosis risk factors was given and measurements of the heel QUS and bone mineral density at the lumbar spine and the proximal femur, obtained by dual-energy X-ray absorptiometry (DXA), were made. Spinal radiographs were assessed for vertebral fractures. Sensitivity, specificity, predictive values, likelihood ratios, and receiver operator characteristics (ROC) curve QUS values were calculated using the optimal threshold identified in the CART models. Cutoff values calculated from best CART model (i.e., a QUS index >90.5%) yielded a sensitivity of 80.3% (95% CI 69.2-88.1), a negative predictive value of 94% (95% CI 90.1-96.5), and a specificity of 68.8% (95% CI 63.3-73.8). This cutoff value would obviate the need to perform DXA in 32.8% of the women of our population at risk for vertebral fractures. The area under the ROC curve of the best model was 0.8071. QUS was shown to discriminate between women with and without a history of vertebral fracture and constitutes a useful tool for assessing vertebral fracture risk. The application of decision trees (CART analyses) was helpful to define the optimal threshold QUS values.

Heel Ultrasound Can Assess Maintenance of Bone Mass in Women With Breast Cancer

Postmenopausal women with early stage breast cancer are at increased risk for bone loss and fractures. Bisphosphonates can prevent bone loss, but little data are available on changes in bone mass assessed by heel quantitative ultrasound (QUS). Our objectives were to determine if (1) heel QUS would provide a reliable and accessible method for evaluation of changes in bone mass in women with breast cancer when compared with the current standard of bone mass measurement, dual-energy X-ray absorptiometry (DXA) and (2) oral risedronate could affect these changes. Eighty-six newly postmenopausal (up to 8yr) women with nonmetastatic breast cancer were randomized to risedronate, 35mg once weekly or placebo. Outcomes were changes in heel QUS bone mass measurements and conventional DXA-derived bone mineral density (BMD). Over 2yr, bone mass assessed by heel QUS remained stable in women on risedronate, whereas women on placebo had a 5.2% decrease (p≤0.05) in heel QUS bone mass. Both total hip BMD and femoral neck BMD assessed by DXA decreased by 1.6% (p≤0.05) in the placebo group and remained stable with risedronate. Spine BMD remained stable in both groups. Heel QUS was moderately associated with BMD measured by DXA at the total hip (r=0.50), femoral neck (r=0.40), and spine (r=0.46) at baseline (all p≤0.001). In conclusion, risedronate helps to maintain skeletal integrity as assessed by heel QUS for women with early stage breast cancer. Heel QUS is associated with DXA-derived BMD at other major axial sites and may be used to follow skeletal health and bone mass changes in these women.

Quantitative ultrasound of the heel and fracture risk assessment: an updated meta-analysis

Meta-analysis of prospective studies shows that quantitative ultrasound of the heel using validated devices predicts risk of different types of fracture with similar performance across different devices and in elderly men and women. These predictions are independent of the risk estimates from hip DXA measures. Clinical utilisation of heel quantitative ultrasound (QUS) depends on its power to predict clinical fractures. This is particularly important in settings that have no access to DXA-derived bone density measurements. We aimed to assess the predictive power of heel QUS for fractures using a meta-analysis approach. We conducted an inverse variance random effects meta-analysis of prospective studies with heel QUS measures at baseline and fracture outcomes in their follow-up. Relative risks (RR) per standard deviation (SD) of different QUS parameters (broadband ultrasound attenuation [BUA], speed of sound [SOS], stiffness index [SI], and quantitative ultrasound index [QUI]) for various fracture outcomes (hip, vertebral, any clinical, any osteoporotic and major osteoporotic fractures) were reported based on study questions. Twenty-one studies including 55,164 women and 13,742 men were included in the meta-analysis with a total follow-up of 279,124 person-years. All four QUS parameters were associated with risk of different fracture. For instance, RR of hip fracture for 1 SD decrease of BUA was 1.69 (95% CI 1.43-2.00), SOS was 1.96 (95% CI 1.64-2.34), SI was 2.26 (95%CI 1.71-2.99) and QUI was 1.99 (95% CI 1.49-2.67). There was marked heterogeneity among studies on hip and any clinical fractures but no evidence of publication bias amongst them. Validated devices from different manufacturers predicted fracture risks with similar performance (meta-regression p values > 0.05 for difference of devices). QUS measures predicted fracture with a similar performance in men and women. Meta-analysis of studies with QUS measures adjusted for hip BMD showed a significant and independent association with fracture risk (RR/SD for BUA = 1.34 [95%CI 1.22-1.49]). This study confirms that heel QUS, using validated devices, predicts risk of different fracture outcomes in elderly men and women. Further research is needed for more widespread utilisation of the heel QUS in clinical settings across the world.

Discriminative Ability of Heel Quantitative Ultrasound in Postmenopausal Women With Prevalent Low-Trauma Fractures: Application of Optimal Threshold Cutoff Values Using CART Models

Quantitative ultrasound (QUS) of the heel has been proposed as a screening tool to evaluate the bone status and risk of osteoporotic fragility fractures. The aim of this study was to define threshold values of QUS that would maximize the predictive ability of this technique to discriminate subjects with fragility fractures. A cross-sectional analysis was made of a cohort of 1132 postmenopausal women with a mean age of 58 yr. A total of 361 women (31.9%) presented with a history of osteoporotic fracture. Most fractures (74.1%) were nonvertebral. For all patients, a questionnaire of osteoporosis risk factors and measurements of the heel QUS and bone mineral density at the lumbar spine and the proximal femur obtained by dual-energy X-ray absorptiometry (DXA) were assessed. Spinal radiographs were assessed for fractures and historical nonvertebral fragility fractures. Sensitivity, specificity, predictive values, likelihood ratios, and receiver operator characteristic (ROC) curve QUS values were calculated using the optimal threshold identified in the classification and regression trees (CART) models. Cutoff values calculated from the best CART model (i.e., a quantitative ultrasound index (QUI) greater than 88.5% in women aged 58 yr or older) yielded 88.8% (95% confidence interval [CI]: 81.4–93.5) for sensitivity, a negative predictive value of 93.8 (95% CI: 89.4–96.4), and 70.4% (95% CI: 64.6–75.7) for specificity. This cutoff value would obviate the need to perform DXA in 43.1% of the population. The area under the ROC curve of the best model was 0.8363 (95% CI: 0.8249–0.8477). In conclusion, QUS was shown to discriminate between women with and without a history of fragility fracture and constitutes a useful tool for assessing fracture risk. The application of decision trees (CART analyses) was helpful to define the optimal threshold QUS values.

Quantitative ultrasound and radiographic absorptiometry are associated with vertebral deformity in Japanese Women: the Hizen–Oshima study

We evaluated the ability of heel quantitative ultrasound (QUS) and metacarpal radiographic absorptiometry (RA) to identify subjects with vertebral deformities in Japanese women aged ≥40. Both QUS and RA were associated with vertebral deformities, and the estimated prevalence at each T-score widely varied with age. Heel QUS and metacarpal RA have been used for screening patients to evaluate risk of osteoporotic fractures. The aim of this study was to evaluate the ability of QUS and RA to identify women with vertebral deformities in 570 Japanese women aged ≥40, and to estimate the prevalence of vertebral deformity at each T-score. Calcaneal QUS and metacarpal RA were performed. Radiographic vertebral deformities were assessed by quantitative morphometry, defined as vertebral heights more than 3 SD below the normal mean. The receiver operating characteristic analysis showed that both calcaneal stiffness index (SI) and metacarpal bone mineral density (BMD) were associated with vertebral deformities. Using the T-score of -2.5 as a cutoff value, the specificity and sensitivity for identifying individuals with vertebral deformities was 65% and 83% for calcaneal SI, and 40% and 88% for metacarpal BMD, respectively. The prevalence of vertebral deformity was estimated using age-adjusted logistic regression models. Women with calcaneal SI T-score of -2.5 had a 2% estimated probability of vertebral deformity at age 40, and 22% at age 80. For metacarpal BMD T-score of -2.5, estimated probability was less than 1% at age 40, and 27% at age 80. Both calcaneal SI and metacarpal BMD were associated with prevalence of vertebral deformity. Furthermore, the prevalence widely varied with age at any given bone value.

Influence of Lifestyle Factors on Quantitative Heel Ultrasound Measurements in Middle-Aged and Elderly Men

We examined the distribution of quantitative heel ultrasound (QUS) parameters in population samples of European men and looked at the influence of lifestyle factors on the occurrence of these parameters. Men aged between 40 and 79years were recruited from eight European centers and invited to attend for an interviewer-assisted questionnaire, assessment of physical performance, and quantitative ultrasound (QUS) of the calcaneus (Hologic; Sahara). The relationships between QUS parameters and lifestyle variables were assessed using linear regression with adjustments for age, center, and weight. Three thousand two hundred fifty-eight men, mean age 60.0years, were included in the analysis. A higher PASE score (upper vs. lower tertile) was associated with a higher BUA (β coefficient=2.44dB/Mhz), SOS (β=6.83m/s), and QUI (β=3.87). Compared to those who were inactive, those who walked or cycled more than an hour per day had a higher BUA (β=3.71dB/Mhz), SOS (β=6.97m/s), and QUI (β=4.50). A longer time to walk 50ft was linked with a lower BUA (β=-0.62dB/Mhz), SOS (β=-1.06m/s), and QUI (β=-0.69). Smoking was associated with a reduction in BUA, SOS, and QUI. There was a U-shaped association with frequency of alcohol consumption. Modification of lifestyle, including increasing physical activity and stopping smoking, may help optimize bone strength and reduce the risk of fracture in middle-aged and elderly European men.

Is QUS or DXA Better for Predicting the 10-Year Absolute Risk of Fracture?

Although quantitative ultrasound (QUS) is known to be correlated with BMD and bone structure, its long-term predictive power for fractures in comparison with DXA is unclear. We examined this in a sample of men and women in the European Prospective Investigation into Cancer (EPIC)-Norfolk who had both heel QUS and hip DXA between 1995 and 1997. From 1455 participants (703 men) 65-76 yr of age at baseline, 79 developed a fracture over 10.3 +/- 1.4 yr of follow-up. In a sex-stratified Cox proportional-hazard model including age, height, body mass index, prior fracture, smoking, alcohol intake, and total hip BMD, a 1 SD decrease in BMD was associated with a hazard ratio (HR) for fracture of 2.26 (95% CI: 1.74-2.95). In the multivariable model with heel broadband ultrasound attenuation (BUA) in place of BMD, HR for a 1 SD decrease in BUA was 2.04 (95% CI: 1.55-2.69). Global measures of model fit showed relative superiority of the BMD model, whereas the area under the receiving operator characteristic (ROC) curve was slightly higher for the BUA model. Using both Cox models with BMD and BUA measures, we calculated exact 10-yr absolute risk of fracture for all participants and categorized them in groups of <5%, 5% to <15%, and >or=15%. Comparison of groupings based on two models showed a total reclassification of 28.8% of participants, with the greatest reclassification (approximately 40%) among the intermediate- and high-risk groups. This study shows that the power of QUS for prediction of fractures among the elderly is at least comparable to that of DXA. Given the feasibility and lower cost of ultrasound measurement in primary care, further studies to develop and validate models for prediction of 10-yr risk of fracture using clinical risk factors and QUS are recommended.

The effect of including quantitative heel ultrasound in models for estimation of 10-year absolute risk of fracture

The role of quantitative ultrasound (QUS) in clinical practice is debatable. An unanswered question is that whether combining QUS and BMD measurements could improve the prediction of fracture risk. We examined this in a sample of men and women in the European Prospective Investigation into Cancer (EPIC)-Norfolk who had both heel QUS and hip DXA between 1995 and 1997 and were followed for any incident fracture up to 2007. From 1455 participants (703 men) aged 65–76 years at baseline, 79 developed a fracture over 10.3±1.4 years of follow-up. Two separate sex-stratified Cox proportional-hazard models were used including clinical risk factors and total hip BMD. Heel broadband ultrasound attenuation (BUA) was also included in the second model. Global measures of model fit, area under ROC curve, and the Hosmer–Lemeshow statistic showed relative superiority of the model including BUA. Using each model, we calculated 10-year absolute risk of fracture for all participants and categorized them in groups of <5%, 5% to <15%, and ≥15%. Comparison of groupings showed a total re-classification of 16.6% of participants after inclusion of BUA with the greatest re-classification (30.7%) among the group with intermediate risk. Adding a QUS measurement to models based on clinical risk factors and BMD improves the predictive power of models and suggests that further attention should be paid to QUS as a clinical tool for fracture risk assessment.