Lower Quantitative Ultrasound Values Research Articles

Low grade inflammation is associated with lower velocity of sound and broadband ultrasound attenuation in older men, but not with bone loss or fracture risk in a longitudinal aging study

ObjectivesElevated systemic levels of pro-inflammatory cytokines involved in the pathogenesis of osteoporosis. Our objective was to investigate whether low grade systemic inflammation was associated with bone markers, bone quality, bone mass and fracture risk in a population of older persons. MethodsSerum interleukin 6 (IL-6), high-sensitivity C-reactive protein (hsCRP) and erythrocyte sedimentation rate (ESR) were measured in 1287 participants of the Longitudinal Aging Study Amsterdam (LASA), a population based study in a representative sample of older men and women (age 76±6.7years). Bone quality was measured by quantitative ultrasound measurements (QUS) at baseline and after 3years at the calcaneus, and bone mineral density was measured by dual-energy X-ray absorptiometry (DXA) at the spine and hip in a subpopulation. Furthermore, the bone markers osteocalcin (OC) and urinary excretion of deoxypyridinoline (DPD) were determined. Incident clinical fractures were recorded during 6years of follow-up. ResultsMultivariable regression analyses revealed higher IL-6 and ESR levels were associated with lower quantitative ultrasound values in older men (β=−0.98; 95% CI −57.72 to −6.42, p<0.05) and (β=−0.221; 95% CI −15.39 to −3.27, p<0.05) respectively at baseline, but not in women. No significant associations were found between inflammatory markers and bone markers, bone loss at the spine or hips, fracture rate or time to fracture. ConclusionElevated inflammatory markers are associated with impaired bone quality in older men, but not in women. No associations were found with the risk for fractures.

Polymorphisms in inflammation associated genes ALOX15 and IL-6 are associated with bone properties in young women and fracture in elderly

PurposeALOX12 and ALOX15 encode arachidonate lipoxygenases which produce lipid metabolites involved in inflammatory processes. Metabolites generated by ALOX12 and ALOX15 can activate the expression of the potent pro-inflammatory cytokine IL-6, and produce endogenous ligands for PPARG. In this study, polymorphisms in ALOX12, ALOX15, IL6 and PPARG were investigated for association with bone properties in young and elderly Swedish women. MethodsThree SNPs in ALOX12, five in ALOX15, one each in IL6 and PPARG were genotyped in the cohorts PEAK-25 (n=1061 women; all 25y) and OPRA (n=1044 women; all 75y). Bone mineral density (BMD) and quantitative ultrasound (QUS) were analyzed in both cohorts; trabecular bone score (TBS) in PEAK-25; bone loss, fracture incidence and serum C-reactive protein (CRP) were assessed in OPRA. ResultsIn the elderly women ALOX15 (rs2619112) was associated with CRP levels (p=0.004) and incident fracture of any type (p=0.014), although not with BMD or ultrasound. In young women, carrying the common T allele (ALOX 15 rs748694) was associated with lower QUS values (p=0.002–0.006). The IL6 SNP was associated with lower BMD in PEAK-25 (femoral neck p=0.034; hip p=0.012). TBS was not associated with variation in any gene. Variants in the ALOX12 and PPARγ were not associated with BMD in either cohort. ConclusionsThis study suggests that variation in inflammation related genes ALOX15 and IL6 was associated with bone microarchitecture and density in young adult women, but appears to be less important in the elderly, despite an observed association with CRP as a marker of inflammation and incident fracture.

Predictive ability of heel quantitative ultrasound for incident fractures: an individual-level meta-analysis.

The relationship between bone quantitative ultrasound (QUS) and fracture risk was estimated in an individual level data meta-analysis of 9 prospective studies of 46,124 individuals and 3018 incident fractures. Low QUS is associated with an increase in fracture risk, including hip fracture. The association with osteoporotic fracture decreases with time. The aim of this meta-analysis was to investigate the association between parameters of QUS and risk of fracture. In an individual-level analysis, we studied participants in nine prospective cohorts from Asia, Europe and North America. Heel broadband ultrasonic attenuation (BUA dB/MHz) and speed of sound (SOS m/s) were measured at baseline. Fractures during follow-up were collected by self-report and in some cohorts confirmed by radiography. An extension of Poisson regression was used to examine the gradient of risk (GR, hazard ratio per 1 SD decrease) between QUS and fracture risk adjusted for age and time since baseline in each cohort. Interactions between QUS and age and time since baseline were explored. Baseline measurements were available in 46,124 men and women, mean age 70 years (range 20-100). Three thousand and eighteen osteoporotic fractures (787 hip fractures) occurred during follow-up of 214,000 person-years. The summary GR for osteoporotic fracture was similar for both BUA (1.45, 95 % confidence intervals (CI) 1.40-1.51) and SOS (1.42, 95 % CI 1.36-1.47). For hip fracture, the respective GRs were 1.69 (95 % CI, 1.56-1.82) and 1.60 (95 % CI, 1.48-1.72). However, the GR was significantly higher for both fracture outcomes at lower baseline BUA and SOS (p < 0.001). The predictive value of QUS was the same for men and women and for all ages (p > 0.20), but the predictive value of both BUA and SOS for osteoporotic fracture decreased with time (p = 0.018 and p = 0.010, respectively). For example, the GR of BUA for osteoporotic fracture, adjusted for age, was 1.51 (95 % CI 1.42-1.61) at 1 year after baseline, but at 5 years, it was 1.36 (95 % CI 1.27-1.46). Our results confirm that quantitative ultrasound is an independent predictor of fracture for men and women particularly at low QUS values.

Osteoporosis Self Assessment Tool for Asian (OSTA) Index in Comparison to Quantitative Ultrasound of the Calcaneal in Predicting Low Bone Density.

Introduction: Osteoporosis represent a worldwide public health problem, frequently resulting in fractures and leading to psychological problem, social consequences, functional limitation and poor quality of life. So it is important to identify those people who have high risk of osteoporosis, in order to reduce the incidence of osteoporotic fractures. The Osteoporosis Self-Assessment Tool for Asians (OSTA) index is a simple tool based on age and body weight. Calcaneal quantitative ultrasound (QUS) is another simple and low-cost instrument used to prescreen osteoporotic subjects. The aim of this study was to correlate between these two screening methods and to validate usefulness of Osteoporosis self assessment tool for Asian ( OSTA) in comparison with QUS of the calcaneum for the prediction of low bone density in Nepalese women. Methods: This was a two-year descriptive observational study comprising 100 subjects performed at TU Teaching Hospital, Kathmandu, Nepal, from 2007 January to 2009 January who completed semi structured questionnaire with subsequent measurement of Quantitative Ultrasound (QUS) of the calcaneum. The sensitivity, specificity, and diagnostic accuracy of OSTA index was validated with the QUS T-score. Results: When the risk category was defined as OSTA index ≤ -1, and low QUS value as t-score ≤ -2.5, the sensitivity, specificity and diagnostic accuracy of the index were 93.3%, 56.5%, and 62% respectively, and the area under the curve was 0.7651. When the low QUS value was taken as t score ≤ -1.0, the sensitivity, speciÞ city and diagnostic accuracy was 85.2%, 89.1% and 87% respectively. Conclusions: The OSTA index, a simple and free risk assessment tool, can be used to estimate the prevalence of low QUS values in Nepalese women and may help to increase awareness and prevention of low bone mineral density. DOI: http://dx.doi.org/10.3126/noaj.v3i2.9524 NOAJ July-December 2013, Vol 3, Issue 2, 20-25

Phalangeal quantitative ultrasound and metabolic control in pre-menopausal women with type 1 diabetes mellitus.

Several studies have reported increased fracture risk in Type 1 diabetes mellitus (T1DM). Quantitative Ultrasound (QUS) provides information on the structure and elastic properties of bone, which are important determinants of fracture risk, along with bone mineral density. To study phalangeal sites by QUS, examine bone turnover markers and analyze association between these factors with metabolic control in a population of pre-menopausal women with T1DM. Thirty-five T1DM pre-menopausal women (mean age 34.5 ± 6.8 yr) attending the Diabetic Outpatients Clinic in the Department of Internal Medicine, University of Messina, were consecutively enrolled and divided into two groups, taking into account the mean value of glycated hemoglobin in the last three years. Twenty healthy age-matched women served as controls. Phalangeal ultrasound measurements [Amplitude Dependent Speed of Sound (AD-SoS), Ultrasound Bone Profile Index (UBPI), TScore, Z-Score] were performed using a DBM Sonic Bone Profiler. Osteocalcin and deoxypyridinoline served as markers of bone formation and bone resorption, respectively. T1DM women with poor metabolic control showed lower phalangeal QUS values compared to healthy controls (p<0.01) and T1DM women with good metabolic control (p<0.05). No significant differences in QUS measurements were detected between T1DM women with good metabolic control and healthy controls. Lower bone formation and increased bone resorption, although not statistically significant, were observed in patients with poor metabolic control in comparison to patients with good metabolic control. Poor metabolic control may worsen the quality of bone in T1DM. Phalangeal QUS could be considered as a tool to screen T1DM women for osteoporosis in pre-menopausal age.

PO9-227 5-LO/LTA4-H PATHWAY AND LTB4 RECEPTORS ARE INCREASE IN PLAQUE OF PATIENTS WITH CAROTID ATHEROSCLEROSIS. ROLE OF LTB4 IN NFKB ACTIVATION

ALOX12 and ALOX15 encode arachidonate lipoxygenases which produce lipid metabolites involved in inflammatory processes. Metabolites generated by ALOX12 and ALOX15 can activate the expression of the potent pro-inflammatory cytokine IL-6, and produce endogenous ligands for PPARG. In this study, polymorphisms in ALOX12, ALOX15, IL6 and PPARG were investigated for association with bone properties in young and elderly Swedish women.Three SNPs in ALOX12, five in ALOX15, one each in IL6 and PPARG were genotyped in the cohorts PEAK-25 (n = 1061 women; all 25 y) and OPRA (n = 1044 women; all 75 y). Bone mineral density (BMD) and quantitative ultrasound (QUS) were analyzed in both cohorts; trabecular bone score (TBS) in PEAK-25; bone loss, fracture incidence and serum C-reactive protein (CRP) were assessed in OPRA.In the elderly women ALOX15 (rs2619112) was associated with CRP levels (p = 0.004) and incident fracture of any type (p = 0.014), although not with BMD or ultrasound. In young women, carrying the common T allele (ALOX 15 rs748694) was associated with lower QUS values (p = 0.002–0.006). The IL6 SNP was associated with lower BMD in PEAK-25 (femoral neck p = 0.034; hip p = 0.012). TBS was not associated with variation in any gene. Variants in the ALOX12 and PPARγ were not associated with BMD in either cohort.This study suggests that variation in inflammation related genes ALOX15 and IL6 was associated with bone microarchitecture and density in young adult women, but appears to be less important in the elderly, despite an observed association with CRP as a marker of inflammation and incident fracture.

Prediction of absolute risk of non-spinal fractures using clinical risk factors and heel quantitative ultrasound

The relationship between osteoporosis risk factors, bone quantitative ultrasound (QUS) and non-spinal fracture risk was estimated in a cohort of 5,201 postmenopausal women from Spain who were prospectively evaluated during three years. Several clinical risk factors and low heel QUS values were independently associated with non-spinal fracture risk. Low-trauma, non-spinal fractures are a growing source of morbidity and mortality in the elderly. The aim of the present study was to examine the association of heel quantitative ultrasound (QUS) and a series of osteoporosis and fracture risk factors, with incident low energy non-spinal fractures in a population of elderly women, and to incorporate them into fracture prediction models. 5,201 women aged 65 or older were enrolled in a three-year cohort study. Participants completed an osteoporosis and fracture risk factors questionnaire. QUS was measured at the heel with a gel-coupled device. Cox-proportional hazard analyses were performed to evaluate the association with the first incident low-trauma non-spinal fracture. Three hundred and eleven women (6.0%) sustained a total of 363 low-trauma fractures, including 133 forearm/wrist, 54 hip, 50 humerus, 37 leg and 17 pelvic fractures. For every standard deviation decrease in the quantitative ultrasound index, the adjusted hazard ratios (95% CI) for any non-vertebral, hip, forearm/wrist, and humerus fractures were 1.31 (1.15-1.49), 1.40 (1.01-1.95), 1.50 (1.19-1.89) and 1.35 (0.97-1.87), respectively. Similar results were observed with other QUS variables. The best predictive models indicated that age, a history of falls, a previous low-trauma fracture, a family history of fracture, a calcium intake from dairy products of less than 250 mg/day, and lower values of QUS parameters were independently associated with the risk of non-spinal fractures. Both clinical risk factors and QUS are independent predictors of risk of fragility non-spinal fractures. A prediction algorithm using these variables was developed to estimate the absolute risk of non-spinal fractures in elderly women in Spain.

Quantitativer Ultraschall

Methods of quantitative ultrasound (QUS) can be used to obtain knowledge about bone fragility. Comprehensive study results exist showing the power of QUS for the estimation of osteoporotic fracture risk. Nevertheless, the variety of technologies, devices, and variables as well as different degrees of validation of the single devices have to be taken into account. Using methods to simulate ultrasound propagation, the complex interaction between ultrasound and bone could be understood and the propagation could be visualized. Preceding widespread clinical use, it has to be clarified if patients with low QUS values will profit from therapy, as it has been shown for DXA. Moreover, the introduction of quality assurance measures is essential. The user should know the limitations of the methods and be able to interpret the results correctly. Applied in an adequate manner QUS methods could then, due to lower costs and absence of ionizing radiation, become important players in osteoporosis management.

Relationship Between Bone Quantitative Ultrasound and Fractures: A Meta-Analysis

The relationship between bone QUS and fracture risk was estimated in a systematic review of data from 14 prospective studies of 47,300 individuals and 2350 incident fractures. In older women, low QUS values were associated with overall fracture risk, low-trauma fractures, and with hip, forearm, and humerus fractures separately. Bone quantitative ultrasound (QUS) has emerged as a promising technique to evaluate bone status. The aim of this study was to determine the association between measurements of QUS with the risk of fracture. A meta-analysis of prospective cohort studies published between 1985 and June 2005 with a baseline measurement of QUS and subsequent follow-up for fractures was carried out. Fourteen separate study populations, consisting of about 47,300 individuals (85.4% women), with about 124,000 person-years of observation and over 2350 fractures, including 653 hip, 529 forearm, and 386 humeral fractures, were analyzed. The main outcome measure was the estimated relative risk of fracture for a decrease in bone QUS parameters of 1 SD below sex- and age-adjusted mean in women. Eleven studies evaluated QUS at the heel, with patella and phalanx (two studies each) and distal radius (one study) being scarcely used. There was not significant heterogeneity among the studies included in the review. Relative risk estimates (95% CI) for overall fractures were 1.55 (1.35-1.78) for each SD decrease in broadband ultrasound attenuation (BUA), 1.63 (1.37-1.93) for speed of sound (SOS), and 1.74 (1.39-2.17) for QUS index/stiffness index (QUI/SI). Risk estimates were similar or slightly higher for hip fractures and low-energy trauma fractures. Humeral and forearm/wrist fractures were also related with lower QUS values. Measurements of bone QUS are significantly associated with nonspinal fracture risk in older women in a similar degree to DXA. QUS may be a valid alternative to evaluate fracture risk in situations where DXA is not accessible.

Quantitative Ultrasound: Use in Screening for Susceptibility to Stress Fractures in Female Army Recruits

QUS measurements were made on 4139 female Army recruits at the beginning of basic training (BT). QUS predicted stress fracture in female recruits as well as it predicts hip fracture in elderly women. Recruits with low QUS values and a history of smoking and not exercising had an extremely high risk of stress fracture. Stress fractures during basic military training (BT) cause morbidity for the recruits and expense for the Military Services. Females have a higher incidence than males. If recruits at high risk for stress fracture could be accurately identified before they began BT, the military might find it advantageous to provide adaptive training programs for them. Currently no accurate methods of risk identification are available. We measured quantitative ultrasound (QUS) in a population sample of female Army recruits to determine if QUS is a useful tool for determining soldiers at high risk of stress fracture during BT. We recruited 93% of the population of female recruits entering BT at Fort Leonard Wood, MO, during a 10-month period. We measured calcaneal QUS and administered a risk factor questionnaire at baseline and ascertained stress fractures during the 8 weeks of BT. Logistic regression was used to calculate relative risk (RR) of stress fracture. The area under the receiver-operating characteristic (ROC) curve was also analyzed to determine the sensitivity and specificity of speed of sound (SOS) in predicting stress fracture. The incidence of stress fracture was 4.7%. SOS was significantly related to the risk of stress fracture. (p < 0.000) The area under the ROC curve was 0.70. The relative risk (RR) of fracture of those in the lowest quintile (Q1) of SOS was 6.7. The highest risk of stress fracture was found in the subgroup of white women in Q1 of SOS who smoked and didn't exercise (RR, 14.4). Over 16% of the fractures occurred in this subgroup, which indicates that about six of these women would need to be assigned to an alternate BT regimen to prevent one stress fracture. The combination of QUS measurements with evaluation of individual risk factors can identify recruits who are at the very highest risk of stress fracture. The military may find these data helpful to determine the cost-effectiveness of alternate BT regimens.

Correlation of osteoporosis screening by quantitative ultrasound of calcaneus and Osteoporosis Self-Assessment Tool for Asians in Taiwanese.

The Osteoporosis Self-Assessment Tool for Asians (OSTA) index, originally developed for use in postmenopausal Asian populations, is an inexpensive, simple tool based on age and body weight. Calcaneal quantitative ultrasound (QUS) is another simple and low-cost instrument used to prescreen osteoporotic subjects. This study investigated the correlation between these 2 screening methods. OSTA indices were calculated in a total of 3,456 women aged 40 to 95 years (mean, 59.5 +/- 11.7 years) selected from a national epidemiological survey of calcaneal QUS in Taiwan. Age was multiplied by -0.2 and body weight by 0.2. Both values were truncated to yield integers, which were then added together, and compared to the QUS results. When the risk category was defined as OSTA index < or = -1, and low QUS value as t-score < or = -2.5, the sensitivity and the specificity of the index were 84.0% and 61.0%, respectively, and the area under the curve was 0.81. According to the OSTA research group's classification, the high-risk subgroup (index < -4) represented 10.7% of the women 40 years or older, the intermediate-risk subgroup (index -1 to -4) 35.0%, and the low-risk subgroup (index > -1) 54.3%. The prevalence of low QUS values was high among the high-risk category (48.5%), and significantly trended downwards among the moderate- and low-risk categories (21.1% vs 4.4%). As the age of the population increased, there was an increasing false-negative rate (p < 0.001) when using OSTA > -1 to predict the normal QUS value. The OSTA index, a simple and free risk assessment tool, can be used to estimate the prevalence of low QUS values in Asian women and may help to increase awareness and prevention of low bone mineral density.

Community-based survey of low quantitative ultrasound values of calcaneus in Taiwan.

This study investigated prevalence and associated-factors of low quantitative ultrasound (QUS) values by screening calcaneal QUS parameters--broadband ultrasound attenuation (BUA) and speed of sound (SOS)--in population samples of three different Taiwanese communities. The study included 6,322 subjects (2,631 male and 3,691 female), aged 31 yr old or more in Shih-Pai (a metropolitan area in northern Taiwan),Yu-Chi (a mountain area in central Taiwan), and A-Lein (a seaside area in southern Taiwan). The overall response rate was 50.2%. The correlation between BUA and SOS was 0.684, p<0.001. From those who responded, we selected 403 subjects aged 31-40 yr as the reference (the young group), and their BUA was 65.34+/-7.91 dB/MHz. The t-score was calculated from the BUA data of our reference group. The percentile of -2.5<t-score<-1.0 and t-score< or =-2.5 in male subjects was 21.4 and 2.9%, respectively, and in female subjects 24.2 and 14.1%, respectively. The BUA of urban area subjects was higher than that of rural area subjects in almost all age-strata, and overweight was noted to be a protective factor. The effect of age-adjusted odds ratio (AOR) on low QUS values in females was significantly increased every 10 yr from 1.55, 5.13, 13.81, 34.29, to 38.14. This survey showed that age-related decreases in calcaneal ultrasonometry, indicating prevalence of low QUS values, were more obvious in female than male subjects. Overall 38.3% of the female Taiwanese had low QUS values, and this is approximately equivalent to the lifetime risk of fracture at the hip, spine, or distal forearm in Caucasian women. The specific t-score designation, as World Health Organization (WHO) criteria, applied to calcaneal QUS are reasonable when the reference group is selected from the same population.

Prevalence and risk factors of low quantitative ultrasound values of calcaneus in Korean elderly women

Quantitative ultrasound (QUS) of bone is a new radiation-free, low-cost method that measures both bone mass and bone quality. This study was performed to establish the normative data of QUS for Korean women and to determine the prevalence and risk factors of low quantitative ultrasound values in a Korean elderly population. We studied 238 healthy women aged 20–29 years working at a hospital, and 552 women over 50 years of age living in six villages of Chung-Up district, a rural area of South Korea, using QUS measurement of bone. Broadband ultrasound attenuation and speed of sound were measured at the calcaneus, and an index combining these factors (stiffness index) was calculated. T-score was calculated from the data of young normal subjects. Of the 552 elderly women, 34.2% had T-scores between −1.0 and −2.5, and 11.8% had T-scores below −2.5. The prevalence of low quantitative ultrasound values increased with older age, longer duration following menopause, lower body mass index, younger age at menopause and smoking. In multiple logistic regression analysis, age (odds ratio = 1.40 per 5 years, P < 0.05), duration following menopause (odds ratio = 1.35 per 5 years, P < 0.05) and body mass index (odds ratio = 0.78 per quartile, P < 0.05) were independently associated with low quantitative ultrasound values. These results suggested that quantitative ultrasound measurement of the calcaneus could be a useful tool for epidemiological surveys of bone mass.

The epidemiology of quantitative ultrasound: a review of the relationships with bone mass, osteoporosis and fracture risk.

Quantitative ultrasound (QUS) is a simple, inexpensive and non-invasive measure of bone which has been used in research settings for the prediction of osteoporosis. This review summarizes the current status of the epidemiology of QUS analysis, including its relationship with bone mineral density (BMD), risk of osteoporotic fracture and risk factors for osteoporosis. Although only moderately correlated with BMD, QUS appears to be as strong a predictor of osteoporotic fracture as BMD and may predict fracture independent of BMD. Risk factors for low QUS, including age, menopause, body composition and physical inactivity, seem to parallel those of low BMD. More longitudinal research is needed to confirm the clinical utility of QUS and more experimental and population-based studies are needed to determine whether the etiology of low QUS values is different from that of low bone mass.