Abstracts from the Second International Symposium on Bone Ultrasonometry for Clinical Practitioners (Germany)

Abstracts from the Second International Symposium on Bone Ultrasonometry for Clinical Practitioners (Germany) Clifford J. Rosen, MD In this edition of the Journal of Clinical Densitometry we have included 44 abstracts from the Second International Symposium on Bone Ultrasonometry for Clinical Practitioners. The editorial board felt very strongly that including these abstracts would provide the reader with an opportunity to remain current in this ever-growing area. We believe that clinical investigations with ultrasound will occupy a growing part of the bone field and will be center stage in subsequent journals. In fact, we are in the enviable position of having established a process for peer review that will allow clinical ultrasound papers to be widely disseminated. Unfortunately, this did not happen with bone density manuscripts, so clinicians were left trying to define utility without a large database. In the upcoming issues of /CD, readers will have the opportunity to see more ultrasound papers. Additionally, the third edition of this year's journal will be devoted t o the full papers presented a t this International Symposium. Quantitative Ultrasound Evaluation of Bone Mineral Status at the Calcaneus in Patients with Eating Disorders Th. A. Abatzi,' J Nijs,' H Borghs,' W Vandereycken,2J Peuskens, and J Dequeker' 'Department of Rheumatology, University Hospital, Pellenberg, University Psychiatric Hospital St. Joseph, Kortenberg, 2PsychiatricClinic Brothers Alexianen, Tienen, Catholic University Leuven Osteoporosis is well-documented in patients with anorexia nervosa. However, the results in patients with bulimia nervosa are controversial.The pathogenesis is still unknown as several factors contribute to the development of brittle bone disease as malnutrition, amenorrhea, hypercortisolemia, and loss of weight. The authors used the quantitative ultrasound technique (QUS) tool for bone evaluation, because QUS parameters are thought to be independent of weight in contrast to DXA density measurements. Fifty-four patients with anorexia nervosa (age range 13-29) consecutively admitted at the psychiatric hospitals were investigated with the Achilles plus densitometer (Lunar, USA) at the nondominant 0 s calcis. Fifteen of the patients were from binge-eatinglpurging type (ANB), 39 from restricting type (ANR), and 19 patients had bulimia nervosa (BN) (18-28) diagnosed according to the criteria of Diagnostic and Statistical Manual of Mental Disorders, 4th ed. of the American Psychiatric Association. The results were compared to the reference values of 165 young, healthy age-matched females and expressed as z-scores (kindly provided by F. Alenfeld and D. Felsenberg, Berlin, unpublished). The data showed that patients with eating disorders, according to the subgroups, have diverging QUS results at the calcaneus. Broadband ultrasound attenuation is significantly lower in ANR (-0.57 ? 1, p < 0.005) and ANB (-0.81 f 0.8, p < 0.005), and significantly higher in the BN (0.55 k 0.1, p c 0.05) group. Speed of sound is significantly higher in the ANR (1.08 f 2, p < 0.005). These differences can be a result of various factors, including bone architecture, degree of mineralization, and other unknown variables between the groups.

Factors Influencing QUS Parameters of the Calcaneum: Suggestions for an Improved Measurement Procedure R Barkmann and CC Gluer

Osteoporosediagnostik Kiel, Radiologische Diagnostik, CAU Kiel, Germany Quantitative Ultrasound (QUS) parameters depend on properties of the surrounding soft tissue and its surface. Factors such as temperature and air bubbles are known to influence water-based BUA and SOS measurements at the

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calcaneum, leading to the need for of careful skin preparation and waiting for stable measurement values. The authors wanted to investigate the influence of air bubbles at the skin and of the temperature of the soft tissue on preparation time and results of QUS measurements. Using the UBIS 3000 that features a temperature stabilized water bath at 3OoC, the authors measured both feet of six healthy objects, six times each, on different days. First, the temperatures of both heel sides were measured using an infrared sensor. Then two alternative preparation procedures were carried out on each foot. One foot was wiped with alcohol according to manufacturer recommendations;then the other foot was immersed into another water bath stabilizedat 30°C and a water beam was directed to both sides of the heel in order to remove air bubbles from the skin. The sequence was changed from day to day. Each foot was measured immediately following this procedure. The UBIS 3000 started scanning when BUA reached an equilibrium. The time of drift between foot immersion and scan start was logged. The time of drift did not depend on temperature, but rather on preparation mode. Preparation using a waterbeam resulted in a significantly reduced time of drift compared to preparation using alcohol (2.4 k 2.0 min vs 4.1 k 2.1 min, mean SD, p < 0.001). BUA and SOS results both significantly depended on temperature but not on preparation mode. The slope was + 0.27 k0.09 dBIMHzI°C,p < 0.01 for BUA and -3.6 f0.5 m/sl°C,p < 0.0001 for SOS vs skin temperature (mean SE slope). Ultrasound parameters are influenced by soft tissue temperature. Even after several minutes of immersion in a temperature-stabilized water bath, BUA and SOS did not reach their final level. A strong drift of BUA within the first minutes did not depend on temperature, but probably on the existence of air bubbles at the surface of the skin. If these results can be confirmed, it might be possible to reduce the measurement time by introducing a different preparation procedure and to increase the precision of BUA and SOS by correcting for differences in skin temperature.

Fracture DiscriminationAbility of Quantitative Ultrasound Measurements at Several Cortical Sites of the Peripheral Skeleton R Barkmann,' D Hans,2 E Kantor~vich,~ C Singa1,3 H K Genant,zM Heller, and CC Gluerl

'Osteoporosediagnostik Kiel, Radiologische Diagnostik, CAU Kiel, Germany; *Osteoporosisand Arthritis Research Group, Department of Radiology, University of California, San Francisco; 3Sunlight Ultrasound Technobgy Ltd., Rehovot, Israel A new instrument measuring ultrasound velocity (Omnisense, Sunlight Ultrasound Technology) in a reflection mode enables measurements at a larger variety of sites, including bones that are not accessible from two opposite sides. The authors investigatedwhether this method offers good fracture discrimination and if a combination of sites can improve this ability. In a first study we measured the phalanx, metacarpal, and radius using a prototype of the Omnisense on 28 women with previous fractures of hip, spine, or forearm (ages 76-81, k 5.0) and 34 controls without fractures (ages 69-51, f 6.5). Discrimination of fractured vs control cases was assessed using age-adjusted regression analysis and ROC analysis. Age-adjusted ODD ratios were 4.14.5 (p < 0.01), and areas under the ROC curve were 0.88-0.89 for the three sites. A combination of all bones increased the area to 0.95. The increase was significant compared to each of the single bones (p < 0.05). Conclusion. QUS measurements in reflection mode at the radius, phalanx, and metacarpal offer good fracture discrimination. A combination improves this ability when compared to single measurements. This study had a small sample size and results were obtained on a prototype device. Further studies are required to confirm the potential of multisite QUS measurements in fracture discrimination.

Comparison of Grip Strength and Digital Quantitative Ultrasound Measurement (QUS) in Elderly People H Bischoff,' D Lindemann,' U Schlonvogt,' R Vonthein,' F HartLz H B Stahelin,' and R TheilerZ

Departments of 'Geriatrics and 2Rheumatology,University Hospital, Basel, Switzerland Introduction. Grip strength is considered to be a good indicator of upper limb strength and functional status. Previous studies have demonstrated a strong relationship between bone mineral density and muscle function. Both parameters were identified as powerful synergistic predictors of fracture incidence. Aim.The purpose of this study was to compare grip strength with digital QUS in elderly women and men. Methods. The authors enrolled 37 residents of a geriatric ward (15 women and 22 men). Mean age was 80.7 yr (range 60-95). Grip strength (GS) was measured by a Martin vigorimeter (rubber bulb, which is grasped by the hand) in a standardized position. Maximal strength out of three measurements, taken at the dominant hand, was documented as ma. A digital ultrasound device (IGEA) was used to measure QUS (speed of sound as SOS in mls and ultrasound bone profile score as UBPS).

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Results. GS declined with age (Y = -0.53; p = 0.0008) and increased with body mass index (BMI; r = 0.37, 0.04). SOS and UBPS correlated highly significant (Y = 0.87; p < 0.0001). Higher values were documented in male subjects for SOS (female mean value in m/s + standard error (SE): 1729.7 + 28.5; male: 1822 + 2 3 . 5 ; ~= 0.017) = 0.001). In a multiple linear regression model, and UBPS (female mean value + SE: 24.7 + 4.1; male: 44.1 + 3 . 4 ; ~ SOS was explained by age (p = 0.21), sex (p = 0.003), BMI (p = 0.73), and GS (p = 0.026). R2of the whole model was 0.32. Similarly, UBPS was explained by age (p = 0.92), sex (O.OOOl), BMI @ = 0.87), and GS (0.015). R2was 0.45. Conclusion. In elderly people, digital QUS, measured as SOS and UPBS, documented higher values in male subjects and was significantly related to grip strength.

p

=

Clinical Evaluation of the Sahara Clinical Bone Sonometer M Bouxsein,’ S Greenspan,’ L Ferguson,’ D Baran,2 P Balikian,2 J Hopkins,* D KieL3 E von Stetten,4 KE W i l ~ o n P, ~Steiger,4 and JA Stein4 ‘Beth Israel Hospital, Boston, MA; 2UMassMedical Center, Worcester, MA; 3HebrewRehab. Center; Boston, MA; and 4Hologic, Inc., Waltham, MA Tho in vivo performane of a waterless calcaneal ultrasound system (Hologic Sahara) was compared to that of a previous generation water-based system (Walter-Sonix UBA 575+), and to that of the standard dual energy X-ray absorptiomety (DXA) technique. Sahara is compact and portable, and allows rapid (1 0 s) radiation-free assessment of bone status and risk for fracture without the complications of a water bath. Diagnostic senhtiviry, short-term measurement precision, and the relationship between Sahara, UBA, and DXA results were investigated. Two hundred forty-seven subjects were recruited at three centers for assignment into one of six groups on the basis of age, facture history, and femur neck DXA t-score: Young healthy (Group 1,’n = 64, age = 30 k 4), Elderly Normal (11, n = 16, age = 62 f 7 ) , Elderly Osteopenic (111, n = 50, age = 66 k 8), Elderly Osteoporotic (IV, n = 57, age = 73 f 8), Elderly Osteoporoticwith fracture (W,n = 25, age =74 f8), and Extremely Elderly (VI, n = 35, age = 91 f 5). Sahara, UBA, heel DXA, and AP spine DXA measurements were performed to compare diagnostic spitivity. Replicate ultrasound measurements (5 Sahara, 3 UBA) were performed with repositioning to assess short-term precision. Intergroup differences expressed as t-scores indicated similar sensitivities to age and clinical status for all ultrasound and DXA parameters. Strong linear correlations were found between all heel results ( R> 0.82), with Sahara vs UBA the strongest ( R = 0.91). Sahara standardized precision (SCV), defined as the precision error divided by the annual loss in a reference population, was superior (2.45) to UBA (SCV = 3.6), but poorer than for AP or neck DXA (SCV = 1-2). It is concluded that diagnostic sensitivity of Sahara results is similar to that of UBA and DXA results and standardized precision values for Sahara are superior to those for the UBA system, but remain poorer than for AP spine or femur neck DXA.

Bone Ultrasonographyand Biochemical Markers of Bone Turnover C Cepollaro, S Gonnelli, A Montagnani, 5 Martini, R Palmieri, C Pondrelli, D Bruni, MS Campagna, and C Gennari Institute of Internal Medicine, University of Siena, Italy In the last years, ultrasound (US) techniques have been widely employed in the assessment of osteoporosis. However, few data have been reported on the relationship between US parameters and bone turnover. The present study was aimed to evaluate the correlation between biochemical markers of bone turnover and US parameters in order to assess if bone markers could be able to predict the variations of US parameters. The authors studied 40 postmenopausal women, osteopenic or osreoporotic without osteoporotic fracture (ages 60.5 k 5.0), who had been treated only with calcium (1000 rng/d) for 4 yr. At baseline and at 12-11-10 intervals, the authors measured BMD at lumbar spine (BMD-LS) and femoral neck (BMD-FN) by dual X-ray absortiometry (DXA) (Hologic QDR lOOO), and speed of sound (SOS), broadband ultrasound attenuation (BUA), and stiffness (S) at the 0 s calcis, by Achilles (Lunar Corp.). At the same time, biochemical markers both of bone formation:alkaline phosphatase (ALP), and bone alkaline phosphatase (bALP), and of bone resorpti0n:urinai-y hydroxyproline (HOP) and urinary a-Crosslaps (a-CrossLaps, RIA, Osteometer Biotech) were also performed. At baseline, biochemical markers did not show any significant correlation with US and BMD. In contrast, significant (p < 0.05) correlation was found between the perceptual changes of SOS and perceptual changes of bALP and a-Crosslaps. No significant correlation was found between perceptual change of BMD and bone markers. In conclusion, longitudinal variations of ultrasound parameters, namely SOS, seem to be related to some biochemical markers of bone turnover. Therefore, the assessment of bone turnover may be useful to predict the pattern of US parameters.

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Clinical Quality Assurance in the Use of QUS Systems: A Proposalof a Cettfication Framework C. Cepollaro,' 5 Gonnelli,' C Gennari,' C Wuster,2 P Heilmann,' and R Theiler3 'Inst. Internal Medicine, University of Siena, Italy; zUniversity of Heidelberg, Germany; and 3Rheumaklinik, Kantonsspital Aarau In this last decade, the number of models of QUS systems and their spread in clinical applications has significantly increased. It appears evident from the practical experience that QUS systems have to be used by properly trained personnel. The knowledge of ultrasound propagation features as well as details of the technique should be known by the user to perform consistent measurements. In addition, it is also mandatory to consider the clinical profile of the subject being measured in order to reach a clinically significant diagnosis. In order to keep a high standard in the use of QUS in the clinical setting, this new medical discipline should be given a structure allowing to transfer, train, and monitor such application. A proposal is shown in the figure.

v \End User

I

II

The authors believe that universities and research centers are the proper candidates to lead the entire educational process as well as to give guidelines for the correct management of results. They should be entitled to certify QUS users as well as "tutors'' who would be capable to train new users. This pattern should be applied to each methodology present, or entering, the market. Manufacturers should therefore be able to provide theoretical and technical information to allow a proper and consistent training of potential users. It could be useful to establish a clinical quality assurance group capable to guarantee a significant and consistent use of QUS devices in the medical community.

Ultrasound and Bone Mineral Density Assessments of the Calcaneus in Normal Early Menopausal Women Sulin Cheng,'**Dennis Taaffe,' Sari Ollikainen,' Harry Genant? and Harri Suominenl 'Department of Health Sciences, University of /yvaskyla, Finland; and ZDeptartment of Radiology, University of California, San Francisco This study investigated the associations between quantitative ultrasound (QUS) and bone mineral densicy of the calcaneus in 80 Caucasian women, ages 50-57 (mean 53 k 2) yr, who were healthy and within 1-5 yr afier the onset of menopause. Using the QUS-1TM Ultrasonometer (Metra Biosystems, Inc.), the authors assessed broadband ultrasound attenuation (BUA and UBI-4, dB/MHz), and amultiple factor index (UBI4T, &/MHz/p). Bone mineral content (BMCu, g/cm), area density (BMD g/cm*), and true density (BMDV g/cm3) were measured by single photon absorptiometry. Computed tomography was used to identify the QUS scanning location. BMClBMD was obtained by scanning calcaneus from the posterior-inferior towards anterior-superior direction (1 1, 13, 15, and 17% of the foot length), matching sites where QUS was performed. The QUS scanning area was graduallyenlarged (79 mm', 105 mm', and 219 mm'). All the QUS variables were significantly correlated with BMC and BMDJBMDv(r = 0.237 - 0.5 17, p = 0.035 <0.001). The significant association between QUS and BMC became stronger with enlarged QUS scanning areas. However, the associationbetween QUS and BMDV showed an opposite relationship.When controlled for the effects of bodyweight and height, the significant correlation between QUS and BMClBMD variables became stronger (T= 0.324 - 0 . 5 4 1 , ~= 0.004 - <0.001). The agreement between QUS variables and BMC or BMD for classifyingsubjects, using three criteria (> -1SD, -lSD to -2SD, and < -2SD), was 79-85% (Kappavalues).The disagreement between QUS and BMC/BMD for classifying those subjects with > -lSD was 7.5-12.5%, -lSD to -2SD was 6.4-1 1.2%, and < -2SD was 0-1.3%. However, <30% variance of BUA can be explained by BMC or BMD in these healthy early menopausal

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women. This low value could be a result of the limited biological range of the subjects studied. There was a 1.45.9% difference in QUS parameters among different scanning areas (paired t-test, p = 0.092 - <0.001). This suggests that controlling reproducible measurements at the same location is important for clinical monitoring. It is necessary to develop a QUS quality control program for comparing different studies, since the same device could provide significantly different results. Caution: QUSl is an investigational device limited by United States law to investigational use.

The Influence of Bone Width on Ultrasound Measurements at the Calcaneus ML Frost, GM Blake, and I Fogelman Osteoporosis Unit, Guy's Hospital, London, UK There is growing evidence that quantitativeultrasound (QUS) can be used to assess skeletal status and predict fracture risk Bone status at the calcaneus can be quantiied by ultrasound attenuation and ultrasound velocity. At present, the UBA575+ (Hologic Inc., Ulaltham, MA) is the only commercial device which measures bone width and provides a measurement of the tme velocity of sound through bone only. The UBA575+ is a water-based system which measures broadband ultrasound attenuation (BUA), the average velocity of sound between the transducers (SOS) and true bone velocity (BV). There are three main objectives to thii study: to examine the distribution of bone widths in a large group of women, to assess whether bone width influences BUA or velocity measurements,and if the diagnosticvalue of velocity measurements is increased by normalizingfor calcaneal width. A total of 739 women (aged 18-82yr, mean 48.1) had QUS measurements on the UBA575+and 558 of these were scanned in duplicate. The distribution of bone widths follow a Gaussian disuibution, with a mean bone width of 30.1 mm and SD of 3.22 mm (Fig. 1).The bone widths ranged from 2 2 4 0 mm. The precision error was 11 mm. Linear regression analysis revealed a significant negative correlation between bone width and both BUA (Y = 0 . 1 7 , ~< 0.0001) and BV (Y = 0 . 3 1 , ~ < 0.0001). The relationship benveen bone width and SOS was not significant (p = 0.43). A highly significant relationship was observed between BV and SOS measurements (Y = 0.95, p < 0.0001). The two measurements of BV and SOS converged at a common velocity of approx 1.495 m/s, which is in the lower part of the ranges of BV and SOS values. This area of low BV and SOS values is particularly important in identlfying patients with osteoporosis. BUA was also significantly correlatedwith BV (Y = 0 . 8 1 , ~< 0.0001).

In conclusion, the negative correlation between bone width and both BUA and BV was not expected, but the typical variability in calcaneal widths is typically only 3 mrn, so the impact on the ultrasound parameters will be small. The SOS and BV measurements are highly correlated and therefore there seems to be no clinical advantage in measuring BV instead of SOS. Estimating bone widths is another source of imprecision, and precision is important in clinical bone densitometry, especiallylongitudinal studies. Unless a marked variability in bone widths is encountered (e.g., pediatric subjects) SOS seems to be a reliable surrogate for measuring velocity of sound in the calcaneus.

Ultrasound Parameters in the Follow Up of Osteoporotic Women Treated with Estrogen 5 Gonnelli, C Cepollaro, C Pondrelli, A Montagnani, B Rossi, M Montomoli, S Pacini, B Lucani, and C Gennari Institute of Internal Medicine, University of Siena, Italy Speed of sound (SOS) and broadband ultrasound attenuation (BUA) of ultrasound in bone have been proposed as alternatives to radiation-based methods for the quantitative assessment of osteoporosis. The authors have previously shown that SOS, BUA, and stiffness (S) are able to monitor osteoporotic patients treated with salmon calcitonin. The aim of the present study was to evaluate the ability of US parameters for monitoring osteoporotic patients treated with estrogen. Eighty osteoporotic women (age range 49-60 yr) were studied. Forty of them were treated for 2 yr with estrogen and calcium (Group 1) and 40 patients were given only calcium (Group 2). At baseline and after 1 and 2 yr,

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the authors measured the BMD at the lumbar spine by DXA (Hologic QDR 1000) and SOS, BUA, and S at the 0s calcis, by Achilles (Lunar Corp.). In Group 1, BMO increased by 3.21%, SOS by 0.26%, BUA by 1.14%, and S by 2.86%. In contrast, subjects in Group 2 decreased in all parameters (BMD -1.71%, SOS -0.44?40, BUA -2.64% and S -4.80%). The differences between groups were significant (p < 0.01) for all parameters. At the end of the study period, changes in BMD and in US parameters significantly correlated (p < 0.001). In conclusion, ultrasound measurements may be helpful also in monitoring the response to estrogen treatment in osteoporotic patients.

Is Quantitative Ultrasound Sonography (QUS) Able to Identify Osteoporosis in Postmenopausal Women? P Hadji, G Emons, and K-D Schulz

Department of Obstetrics and Gynecology, University of Marburg, Germany The aim of this study was to determine if QUS at the calcaneus is able to identify osteoporosis of postmenopausal women in gynecologicalpractice. Speed of sound (SOS), broadband ultrasound attenuation (BUA), and stiffness index (SI) of the calcaneus were measured in n = 764 postmenopausal women, mean age 61 yr, using the Achilles ultrasound bone densitometer (Lunar Corp., Madison, WI). In addition, the authors measured blood levels of E2 and FSH in 157 women. Osteoporotic risk factors were assessed by a detailed questionnaire. Women using any medication known to affect bone metabolism were excluded from the study. Shorc-term precision in vivo expressed as coefficient ofvariance (CV) was 1.2% for BUA, 0.17% for SOS, and 1.3% for stiffness, respectively. A total of 102women were measured at the right and left calcaneus with a coefficient of correlationof Y = 0.92 for SOS, r = 0.84 for BUA, and r = 0.93 for SI (V I 0.001). There was a significant yearly postmenopausaldecrease of 0.06% for SOS, 0.44% for BUA, and 0.74% for SI (V I 0.001). One hundred sixty-fivewomen with a history of osteoporosis (identifiedby DXA or Qcr) according to t h e w 0 criteria, as well as 141women with an osteoporosis-related fractureof the spine, hip, or the distal forearm, shaved significantlylaver results in all ultrasound parameters (SOS, BUA, SI) (V I 0.00 1). In conclusion, quantitative ultrasound sonography of the calcaneus measures properties of bone that show a physiological postmenopausal decline, a low precision error, and a high correlation of right vs left. These results indicate that QUS is able to identify postmenopausal women with a history of osteoporosis as well as women with previous osteoporotic fractures.

A New Alternative in Quantitative Ultrasound to Improve Discrimination of Hip Fracture Using a Bone Ultrasonometer at Multiple Measurement Sites D Hans,’ SK Srivastav,’ CF Njeh,’ C SingaL2C Wu, E Kantorovich,2 and HK Genant’ ‘Osteoporosis and Arthritis Research Group, University of California, San Francisco; 2Sunlight Ultrasound TechnologiesLtd., Rehovot, Israel The newly introduced Omnisense prototype (Sunlight Ltd., Israel) is a breakthrough bone ultrasonometer that can be used on multisite bone, including major osteoporosis fracture sites. In this study, the authors determined if a combination of ultrasound velocity results, obtained from different measurement sites, was able to improve hip fracture discrimination over a single site. Twenty to seventy-nine female subjects with recent hip fractures (<6 mo) (mean age 79-89 yr) and 64-295 controls without fractures (mean age 70-87 yr) were included in the study. SOS measurements at the calcaneus, distal third, and ultradistal radius hand phalanges, metacarpal, and capitate, patella, and the posterior process of the lumbar spine were performed. Precision (RMSCV, SCV) as well as hip fracture discrimination were assessed by odds ratio and area under the ROC curve (AUC) using age and BMI-adjusted logistic regression analysis. The best combination, using stepwise logistic regression, has been carried out.

Abstracts

Conclusion: The authors found that the combination of the distal 113 of the radius and the calcaneus significantly improves the sensitivity, the specificity, and the overall accuracy. Combining different ultrasound sites to improve fracture discrimination could be a new alternative that requires further confirmation.

Imaging Quantitative Ultrasound Differs in Patients with Osteoporosis from Normals

P Vargha3

Cs K Horvath,’ 5 Meszaros,2K Bors,4 E HOSSZU,~ I Krasznai,’ J Szucs,’ and

’1st Department of Medicine, 22nd Department of Pediatrics, Biometric Centre Semmelweis University Medical School and 4Ferencvaros Osteoporosis Centre, Budapest, Hungary To determine the utility of imaging ultrasound as the newest diagnostic tool for osteoporosis, we measured BOA and SOS by DTU-ONE (Osteometer) in patients referred as osteoporotics and sent to measure bone densities. BMD was assessed at spine and hip by DEXA (DPX-L, Lunar) and at radius by SPA (NK-364, Gamma). One hundred forty-two patients were studied: 113women and 29 men, aged 20-76 yr. They were classified as normals (spine BMD T-score > -I), patients with osteoporosis (T <-2.5), or osteopenia (T between -1 and -2.5). Correlatons between BUA and BMD were near to those usually obtained between BMD at different bone sites: spine I = 0.45 in females QJ < 0.0001) and 0.38 in males (p < 0.04), hip 0.51 (p < 0.0001) and 0.62 (p < O.OOOl), radius 0.44 (p < 0.0001) and 0.26 @J = 0.13), respectively. Weak but significant correlationswere shown between SOS and BMD as well: spine 0.44 in females (D < 0.0001) and 0.22 in males (D = 0.26),hip 0.52 (D < 0.0001) and 0.52 @< 0.004),radius 0.32 (p < 0.0001) and 0.22 (p = 0.20), respectively. Ultrasound results (n)at the left 0 s calcis were found as follows: For BUA Spine Hip Radius

Normal

Osteopenia

Osteoporosis

46.1 k 1.3 (42) 45.7 f 1.3 (50) 45.9 f 1.3 (45)

40.7 f 1.3 (45) 39.2 f 1.0 (74) 40.1 + 1.4 (44)

35.8 f 1.3 (55) 31.0 k2.3 (18) 36.0 f 1.3 (53)

(p < 0.0001 for all three sites, ANOVA) For SOS

Spine Hip Radius

Normal

Osteopenia

Osteoporosis

1553.8 k 1.5 1553.7 f 1.4 1551.7 f 1.7

1544.1 f 1.6 1542.6 f 1.1 1545.0 f 1.7

1542.0 rf: 1.4 1539.7 rf: 2.1 1542.3 f 1.3

(p < 0.001 for all three sites, ANOVA) Imaging ultrasound at the heel produced highly significant differences among patients with differerent categories of BMD. The differences seemed to be more expressed for BUA than for SOS. Our data suggest imaging ultrasound to be a useful tool in the diagnosis of patients with osteoporosis.

Decreased BUA but not 505 in Streak Gonad Syndrome E HOSSZU,~ Cs K Horvath,’ 5 Meszaros,’ J Zseli,’ and I Hollo

’1st Dept of Medicine and 22nd Dept of Pediatrics, Semmelweis University Medical School, Budapest, Hungary

Quantitative ultrasonometry (QUS) is a new method for bone assessment. However, it has remained less certain until now what BUA and SOS mean. The theory for ultrasound velocity includes density and a nonmass factor but the latter is not included for BUA. In some reported experiences, attenuation seemed to be a surrogate for tensity only. In the author‘s previous work, the comparison of QUS parameters in young and middle aged females with singular BMD levels resulted in no difference in BUA between the groups but in much lower SOS aged than in young women. In this study, the authors measured bone marrow density and QUS in women with streak gonad syndrome. According to our previous observation, this condition usually includes decreased BMD, but fracture are uncommon even if the density is very low. Sixteen women with streak gonad syndrome, aged 27-55 (mean 39.5 f 2.5), were studied. BMD at lumbar spine and hip was assessed by DEXA (DPX-L, LuDar, WI)and at radius by SPA (NK-364, Gamma, Hungary). BUA and SOS was measured at the left 0 s calcis using DTU-ONE (Osteometer, Denmark). The results expressed in form of Z scores and T scores @-levels) for BMD: Spine

Z score T score

-1.79 f 0.28 (10-5) -2.67 k 0.39 (lo4)

Femoral neck -1 .96 f 0.27 (lo4) -2.48 k 0.35 (10-6)

Radius -1.48 k0.41(10-3) -2.10 k0.46 (lo4)

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The QUS results expressed in the same form (p)

Z score T score

BUA

sos

-3.24 kO.46 (10") -3.24 k 0.46 lo-?

-0.47 10.23 (NS) -0.46 k 0.23 (NS)

High correlation (I = 0.62-0.76,~< 0.01-0.001) was shown between QUS (BUA and SOS) and BMD at spine or hip but not between QUS and BMD at radius (v = 0.31 - 0.50, NS). Our data show discordances between attenuation and velocity in a condition with low density but no fractures. The authors suggest that speed of ultrasound may, in part, also reflect the quality of bone.

Ultrasound Measurements of Phalanges in Children Population: follow-up After 1 Year Z Halaba, W Pluskiewicz, and B Drozdzowska

Silesian Academy of Medicine, Katowice, Poland The aim of the study was evaluationof bone status in Polish children population using ultrasound measurement (US). Materials. One hundred ninety-six children (118 girls and 78 boys) were divided into age groups from 10-15 yr to be studied. In children studied, no factors affecting bone status were noted. All children were measured 1 yr after the first examination. Methods. Skeletal status was assessed using DBM Sonic 1200 (Igea, Italy). Proximal phalanges 11-Vof the dominant hand were measured. Result was expressed in amplitude-dependent speed of sound (AD-SoS) (mls). All measurements were done by one operator. In vivo short-term CV% was 0.64. Results. B = 1st measurement; A = measurement after 1 yr.

GirMBoys age, years 10 11 12 13 14 15

B A B A B A B A B A B A

AD-SoS 194211937 196611952 194011952 196411966 195311932 198011940 198011928 202611951 200011949 204811979 202812026 207112075

Increase in AD-SoS (m/s) 24115 24/14 2718 46/23 48130 43149

P 0.00131 NS 0.00051 0.009 0.000041 0.009 0.0000021 0.0015 0.0000011 0.00014 0.0000151 0.0003

Conclusions. US measurements in proximal phalanges are able to detect growth-related bone changes. In all age groups, a significant increase in AD-SoS was noted except in 10-yr-old boys.

Quantitative Ultrasound Measurements: Can QUS Detect Longitudinal Changes? BM Ingle, YM Henry, KE Sherwood, and R Eastell

Bone Research Group, Division of Clinical Sciences, University o f Shefffield, UK A number of standardized methods have been proposed to permit the comparison of QUS machines in their ability to detect longitudinal changes. The aim of this study was to see if QUS could detect longitudinal changes in the individual based on the standardized precision method proposed by Gliier. The authors measured 175 women ages 21-80 yr (mean 49). Duplicate measurements were made on the Lunar Achilles+ (LA+), Hologic Sahara (HS), CUBA Clinical (CC) (calcaneus), and DBM Sonic (DBM) (finger) ultrasound machines. They calculated (i) the change p.a. from QUS at age 21 and 80 yr, predicted from the linear or quadratic relationship between QUS and age, (ii) precision error based on duplicate measurements, (iii) the standardized precision error from the cross-sectional data (sPECC= precision errorlchange pa), (iv) monitoring time intervals (MTI = 2*42*precision errorlchange pa). The results are shown in the table below.

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Change Precision (pa) Error 1.03 1.62 0.59 3.19 0.30 0.35 0.18 0.48 0.31

LA+ SOS, nVs CC SOS, mls HS SOS, m/s DBM SOS, mls LA+ BUA, dB1MHz CC BUA, dB/MHz HS BUA, dB/MHz IA+Stiff index HS QUI index

1.15 3.80 2.00 7.99 1.25 2.20 1.36 0.95 1.05

sPEcc (yr)

MTI (yr)

1.09 2.32 3.32 2.5 4.16 6.28 7.5 1.97 3.38

3.0 7.0 9.0 7.0 12.0 17.0 21.0 6.0 9.0

The monitoring time intervals were shorter for SOS than BUA. The shortest monitoring time interval was 3 yr for LA+SOS. The longest monitoring time interval was 21 yr for HS BUA. These data suggest that SOS is better for monitoring longitudinal changes.

Problems in the Choice of Material for Quantitative Ultrasound Phantoms

’

SA Jackson, Q Ji,’ J Filipow,’ and J Caminis2 ‘University of Alberta and 2McGill University The rapid development of QUS devices for measuring BUA and VOS of the 0s calcis has produced a range of technologies with no standard reference for quality control and cross-calibration. Several attempts have been made to find suitable material which is both stable and acoustically appropriate; none have yet been adopted. Simple rubber test objects can be easily produced with a range of densities and acoustic parameterswhich fell into the clinical range for BUA and VOS and the fiequency attenuation characteristics are linear over the range of 0.2-1.0. Whereas a simple object such as this is suitable as a consistency check for an instrument, it is unsuitable as a standard since correlation between different devices does not produce a regression which follows that of human data and hence excludes this material for use in cross-calibration. The search for objects with internal structure which mimic bone in its acoustic attenuation and scattering characteristics has not yet been successful. The recently developed “Vancouver Phantom” consists of an open pore structure of reticulated vitreous carbon (RVC) with a mineral oil filling the pore space. This material can be repeatedly produced with varying porosity and density. However, a nonlinear frequencyresponse is exhibitedover the clinical range which causes inconsistenciesbetween different manufacturer equipment in the measurement of BUA. In addition, the VOS does not vary with density. A similar product to the RVC with an aluminum open-celled structure has been studied here, and has provided valuable insights into sound propagation in porous objects. First, the longitudinal pulse exhibits both fast and slow propagation modes which agree with predictions of Biot’s theory, and the phase velocity exhibits a strong dispersion at the lower frequency as the structural density increases. Second, the frequency attenuation shows a linear response, but becomes nonlinear with increasing density. Both of these findings suggest that subtle differences in measurement techniques and analysis algorithms could be the main cause of inconsistency between the different types of device measuring the same object, and that it may be necessary to standardize the analytical method before any standard test object can be chosen.

Quantitative Ultrasound Can Improve Classification of Fracture Status SA Jackson,’ L Robertson,’ J Caminis,2 and A Tenhouse2 l University of Alberta and 2McGill University Hospital Centre, Quebec, Canada The ultimate goal of bone quality assessment techniques is to quantify the risk of future fracture. Intuitively, these same techniques should be sensitive to the prevalent fracture status or recent past fracture history. However, the continuous variables of BMD and QUS show considerable overlap between subjects both with and without fractures of the spine, hip, or wrist. This fact makes it difficult to define a threshold below which a fracture can be reliably predicted to occur. This study examines the ability of SMD and QUS to define fracture status and thus potential for future fracture, in a random group of 406 females taken from the Canadian Multicentre Osteoporosis Study. The study group had a mean age of 65 (minimum 50, maximum 92). Each subject had BMD of the spine and hip, QUS of the heel and lateral spine radiographs. Fracture status of the spine was determined by quantitative morphometry, and other sites by personal history. The percentage of subjects with incident spine fractures was approx 20%, which is in agreement with other population-based studies. Overall fracture history at any site, hip, rib, wrist, or spine, was 33%. BMD and BUA values showed a highly significant correlation with age and with each other, r = 0.6 (p < 0.001). BUA of the heel correlated slightly better with the hip BMD than with the spine.

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Fracture was defined in two ways. First the spine was considered alone, and second, the combined spine status was considered with hip, wrist, and rib history. The ability to discriminate the two groups, fracture and no fracture, on the basis of BMD and QUS parameters was examined. Using the WHO criteria of T = -2.5 as a threshold for both fracture scenarios, the best discrimination was achieved using a combined condition of low hip BMD and heel BUA. The combination was able to detect over 60% of the fractures at this level as opposed to 42% using the spine BMD alone and 49% using the hip BMD alone. By combining the hip BMD and the heel BUA, the ability to discriminare fracture status is significantly improved ( p < 0.05) in this sample. Further continuation of this work will determine if combining bone measurement modalities provides a more powerful predictor of future fracture risk than using density measures alone.

Side Differences in Heel QUS and Relation to Weight-Bearing Load P KasalicG, J Kocian, and L Adamova

1st Med. Clinic Postgrad. Medical School, Prague Czech Republic The questions ofwhich side (when measuring one side only) should be measured and if any side-matched difference in ultrasound parameters exists are investigated in this article. The authors measured QUS parameters of 17 1 patients on both heels by Achilles Lunar ultrasound densitometer. No statistically significant difference between right and left existed in the sample used. The authors noted large differencesin ultrasound parameters of both heels (patients exceeding 30% side ”stiffness” difference were in the author’s sample). The sample had Gauss distribution, with mean value about 0 difference. For this reason, the authors did not confirm the necessity of measuring nondominant leg. They tested the hypothesis, that difference in weight-bearing load of the two legs could cause difference of QUS parameters. Forty-one patients were measured standing on two scales (with each leg on one scale) and were asked to assume their normal posture. The authors then measured weight on each scale and calculated the difference. The maximal difference of weight-bearing load between both legs in the sample was 19 kg, with a slightly higher load on right leg. After statistic evaluation of side weight-bearing differenceswith comparison of ultrasound parameters differences (BUA, SOS, and “stiffness”),they found no correlation between these parameters (rwas about 0.10 for all measured parameters). Despite the fact that the sample was not large, the absolute lack of correlation argues against the possibility of choosing the “weaker”or “stronger”leg according to the side weight-bearing load. The problem still remains as to which value should be used for patients management in cases of large side differences.

Ultrasound Bone Densitometry: Five Years’ Experience with Achilles Lunar system in Diagnosis of Secondary Osteoporosis and Osteomalacia D Kocian and P Kasaliclj

Chair of Internal Medicine Postgrad. Med. lnst. Prague, Czech Republic The lowest values of “stiffness” (parameter calculated as 0.61 BUA + 0.28 SOS - 420) were found in patients with osteomalacia (values between 45 and 55% AM-the diagnosis has to be confirmed by laboratory tests and X-ray), then immobilized patients ( ~ 7 0 % AM), followed by patients with idiopathic hypercalciuria (72-75% AM) lactose-intolerant patients, women undergoing ovariectomy in fertile age, patients treated with glucocorticoids and with malabsorption (between 75 and 80% AM),and postmenopausal women (8045% AM). The device was also employed to follow up therapy. Best results were obtained with vitamin D in osteomalacia-increase about 7-1 5% AM/yr, idiopathic hypercalciuria treated with thiazide diureticsand immobilizedpatients with early rehabilitation, ovarectomizedwomen treated with HRT. Correlation coefficient between Q-US and vertebral DEXA (Norland XR-26) is r = 0.7472 for men and r = 0.8602 for women; between Q-US and femoral neck DEXA, r = 0.7772 for men and r = 0.7288 for women. Main advantages include simplicity of examination and no exposure to radiation.

Quantitative Ultrasound Bone Assessment of the Tibia: Normative Data for a Pediatric 6 to 19 Years Caucasian Population MH Lequin,’RR van Rijn,z SGF Robben,’ DD Keit~an,~ and C van K ~ i j k , ~ . ~

Departments of ‘Pediatric Radiology, University Children‘s Hospital ‘Sophia:. ZExperimentalRadiology, Erasmus University Rotterdam, The Netherlands; 3Myriad Ultrasound Systems Ltd., Rehovot, Israel; and 40steoporosisand Arthritis Research Group, University of California, San Francisco Introduction. Bone densitometry in children is a relative new interest in the field of bone densitometry. Tibial Quantitative Ultrasound bone assessment is a method that potentially be implemented in this specific population

103

Abstracts

(1). In recent years, this method has been validated for the adult population but not yet in a pediatric population. The aim of this study is to validate this method for a pediatric population and generate normal values for the SoundscanTM Compact (Myriad Ultrasound Systems Ltd., Rehovot, Israel). Material and Method. Five hundred ninety-two children (305 girls, age range 6.1-19.9 yr, mean age 12.9 yr; and 287 boys, age range 6.1-19.6 yr, mean age 12.3 yr) were included in our study. In all cases, informed consent was obtained. For each subject, age, weight, height, and Tanner stage were assessed. A patient questionnaire was also completed. Tibial quantitative ultrasound bone assessment, using the Soundscan Compact, was performed on the right mid-tibial site. Results. Strong correlation was found between calendar age and SOS: boys ? = 0.47 and girls ? = 0.62. Correlation between skeletal age and SOS were also strong: boys ?= 0.48 and girls ? = 0.62 (all correlationsp < 0.001). Discussion. Results show that tibia1 ultrasound bone densitometry can be used in a pediatric population. Further investigations into the clinical applications are ongoing at their department. The use of skeletal age normal values; provides an opportunity to employ this method in children who show a dissociation between calendar and skeletal age. References. 1. Foldes AJ, Rimon A, Keinan DD, Popovitzer MM. 1995 Bone 17(4):363-367.

Comparison of Ultrasound and Quantitative Single Energy Computed Topography in Estimating Bone Mineral Density I Maresch, T Frede, B Munsterer, M Daniaux, G Helweg, and D zur Nedden Department of Radiology 11, University Hospital Innsbruck, Austria Purpose. To ascertain the value of ultrasound (US) in comparison to the gold standard computed tomography (CT) in the assessment of bone mineral density. Method. Bone mineral density (BMD) measurements of the calcaneous bone, including speed of sound (SOS) and broad band US attenuation (BUA), were performed with the Lunar@Ultrasound densitometer. The results were compared to both cortical and trabecular bone measurements employing quantitative single energy CT of the lumbar spine. A total of 56 patients, 43 female and 13 male, were examined with both modalities. Results. Both methods showed agreement in only 35 of the 56 cases (62.5%). In women, 30 of the 43 examinations agreed (70%), whereas in men only 5 of the 13 (38.5%) were in agreement. All C T values were compared to the existing standard for healthy young females. Of the eight noncorresponding males, five were osteoporotic and three nonosteoporotic by CT. The Kappa score analysis for the entire group confirms this poor correlation ( K = 0.15). When seperated by sex, the female group shows a somewhat better correlation ( K =0.32 = fair). Conclusion. This study demonstrates only a fair correlation of bone density measurements between the US of the heel bone and C T of the lumbar spine in females. The correlation is even less in males.

Usefulness of Quantitative Ultrasound in Chronic Hemodialysis Patients T Masud, MW Taal, D Green, and MJD Cassidy

Departments of Medicine, Radiology and Nephrology, City Hospital, Nottingham, UK Renal osteodystrophy and osteoporosis result in considerable morbidity and occasional mortality in chronic renal failure patients. The diagnosis of renal bone disease currently relies on clinical suspicion combined with assessment of blood levels of divalent ions, alkaline phosphatase, immunoreactive parathyroid hormone, and bone radiobgy. More accurate methods of determining bone disease either involve bone biopsy, which is invasive, or dual enerby X-ray absorptiometry (DXA), which is not readily available in some areas. The aim of this study was to compare quantitative ultrasound (QUS) at the heel with DXA measurements in a heterogeneous group of chronic hemodialysis patients (n = 88, age range = 18-87 yr, males = 48). QUS (McCue CUBA 11) measured broadband ultrasound attenuation (BUA) and velocity of sound (VOS) at the heel, and DXA (Lunar Expert) measured BMD at the lumbar spine and hip. Broadband ultrasound attenuation was significantly correlated with total hip ( r = 0.79), femoral neck ( r = 0.72), and lumbar spine (r = 0.45) BMDs (p < 0.001). Velocity of sound was significantly correlated with total hip (r = 0.72), femoral neck ( r = 0.68) (p < 0.001), and lumbar spine ( r = 0 . 3 1 , ~=0.003) BMD. Using femoral neck BMD as the standard to diagnose osteoporosis (WHO criteria: T I -2.5), and using the same criteria for QUS to diagnose osteoporosis ( T I 2.5: manufacturer’sreference range), the sensitivityand specificity of BUA in diagnosing osteoporosis were 94.1 and 71.8%, respectively. For the combined endpoint of diagnosing osteopenia or osteoporosis ( T I l.O), the sensitivity and specificityof BUA were 95.0 and 32.1%, respectively. Velocity of sound performed poorly and had a sensitivity of 0% and specificity of 100% for diagnosing osteoporosis. The prevalence of femoral neck BMD diagnosed osteopenia and osteoporosis were 48.9 and 19.3%, respectively. This study suggests that in chronic hemodialysis patients QUS (BUA) is a convenient and sensitive method of identifying patients who require further investigation with DXA andlor bone biopsy.

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Spring 1998

Ultrasound in the Diagnosis and Monitoring of Renal Osteodystrophy A Montagnani, 5 Gonnelli, C Cepollaro, 5 Martini, MB Franci, R Monaco, M Mangeri, and C Gennari

Institute of Internal Medicine, University of Siena, Italy Renal osteodistrophy (ROD) is a bone disease characterized by a wide spectrum of abnormalities ranging from high bone turnover, such as osteite fibrosa, to low bone turnover status, such as aluminum or adynamic bone disease. However, both aspects can coexist in a mixed bone disease. To date, bone biopsy remains the gold standard for diagnosis of ROD, although because of its invasivenessit cannot be a useful tool for monitoring of ROD. Ultrasound techniques (US) have been demonstrated to give information not only on bone density, but also on bone quality. In order to evaluate US parameters in ROD and to study if US are able to distinguish between high and low bone turnover according to biochemical marker, the authors measured US at two different skeletal sites in 98 patients (57 male and 41 female) on maintenance dialysis (HD) and in 104 (54 male and 50 female) healthy subjects, sex and age matched. Ultrasound techniques were performed at proximal phalanxes of hands using DBM Sonic (Igea, Carpi, Italy) and at calcaneous by Sahara (Hologic, Waltham, USA). Additionally, parathyroid hormone (iPTH), total alkaline phosphatase (T-ALP) and its bone isoenzyme (B-ALP), and carboxy-terminal telopeptide of collagen of type I1 (ICTP) was measured in all subjects. In the HD group, US parameters were significantly reduced and bone turnover markers were higher than in healthy subjects. Both amplitude-dependent speed of sound (AD-SoS) and ultrasound bone performance score (UBPS) were significantly reduced in the side of arterial-venous fistula than in the other hand. In the H D group, all US parameters showed good correlation with each other. Among bone turnover markers, only T-ALP and BALP correlated with US. A negative correlation was found between dialytic age and phalanxes US parameters adjusted for patients age. O n the basis of biochemical markers, the authors split H D patients in high bone turnover (HT) and low bone turnover (LT). Amplitude-dependent speed of sound and UBPS resulted significantly (p < 0.05 a n d p < 0.01, respectively) lower in the HT group. In HT, AD-SoS and UBPS showed a good correlation with B-ALP and PTH, whereas in the LT group all US parameters and biochemical markers showed a modest but significant correlation. The authors conclude that US parameters result reduced and correlate with bone turnover markers in H D patients and that AD-SoS and UBPS distinguish between HT and LT according to biochemical markers. Therefore, US measurements could be useful in the diagnosis and follow-up of ROD.

Stiffness Compensates for Effects in Ultrasonometry R Morris, RB Mazess, J Trempe, and JA Hanson

Numerous studies have shown that stiffness, the combination of BUA and SOS, h& better precision in vivo than either of the two variables alone. One reason is that stiffness compensates for the effect of variation in heel width on BUA end SOS. Other variability factors are improved by the use of stiffness. Temperature can be easily compensated for, but this correction does not include heel core temperature, which can vary with environmental conditions and circulation. The authors investigated the effects of heel core temperature and skin-wetting on obtaining precise ultrasound results. A 38-yr-old male was measured with an Achilles+ (Lunar Corp., Madison, WI).The footwell portion of the ultrasonometer was immersed in two constant temperature water baths sequentially.The water baths were maintained at 40 and 21OC throughout the experiment. Temperature of the heel in air at room temperature was 34°C. The subject's heel was first placed in the 40°C footwell for 12 min, followed immediately by 50 min in the 21 "C water bath. Differences in SOS due to the water temperature were removed; thus all SOS changes are a result of heel temperature. Initially,SOS decreased from 1565 to 1555 mls in the 40°C water bath, and BUA increased from 127 to 130 dB/MHz as the heel heated; stiffness was constant at 102. During the exposure at 2loC, SOS increased from 1555 to 1568 m/s, while BUA decreased from 130 to 125 dH/MHz, stiffness increased by only 1%. Data from 68 subjects were also analyzed to determine the length of time for BUA, SDS, and stiffness to reach an asymptote. It takes from 2-6 min for BUA and SOS to approximate a stable asymptote even with a constant temperature water bath. Convergence for stiffness is achieved in a shorter time and in a higher percentage of subjects than for BUA and SOS alone. About 75% of subjects reach asymptote in 2-3 min. The final value can be estimated from a series of measurements made within the first minute. Changes of a few degrees Celsius in heel temperature changed SOS by approx 10 min/s and BUA by approx 3 dB/ MHz. The changes of SOS and BUA are equivalent to 5X the annual decrease observed in these variables in postmenopausal women. However, these changes are in opposite directions, so stiffness is relatively unaffected. For optimal precision, ultrasound measurements should be done in a temperature-controlled water bath with the heel in thermal equilibrium. Use of stiffness provides immunity from thermal effect. Convergence takes several minutes. Shorter measurements compromise both precision and accuracy. Use of stiffness allows use of shorter measurement times without compromising precision and accuracy.

105

Abstracts QUS Measurement at Multiple Sites Discriminates Osteoporotic Fractures CF Njeh,’ D Hans,’ C Wu,’ C Singal,’ E Kantorovich? and H K Genant’

‘Osteoporosis and Arthritis Research Group, University of California, San Francisco, CA; and 2Sunlight Ultrasound Technology Ltd., Rehovot, Israel Whereas most of the commercialized ultrasound devices measure only one site, the Omnisense (Sunlight Ltd., Rehovot, Israel) device measures velocity using a “reflection” mode at multiple sites. However, some of the sites are still under development and are not available for this project. In this study, the authors examined the ability of SOS measured at different axial and peripheral skeletal sites to discriminate between subjects with hip fractures and subjects with all types of fractures from normal controls. Forty-six to 92 subjectswith osteoporoticfractures (mean age 79 86),including 20-68 recent hip fractures (<6mo) and 64-295 controls without fractures (mean age 73 lo), were included in the study. None of these women had any history of bone disease other than osteoporosis or treatment known to affect bone metabolism. Ultrasound measurements were performed at the calcaneus, radius 1/3, ultradistal, the proximal phalanx of the third finger, the hand metacarpal, the patella, the hand capitale, and the posterior processes of the thoracic spine. Discrimination of fractured vs control cases was assessed using logistic regression analysis (expressed as age and BMI-adjusted odds ratios per standard deviation decrease with 95% confidence intervals). Area under the ROC curve was also calculated (AUC).

*

*

Site

OR“ (95% CI)

AUC“

All fractures OR“ (95% CI)

Radius UD Radius 1/3 Metacarpal Patella Hand capitale Third phalanx Thoracic spine Calcaneus

1.5 (1.0-2.2) 12.4 (1.44.1) 1.4 (0.9- 2.1) 1.9 (1.2-3.0) 1.5 (1.0- 2.1) 2.0 (1.4-3.0) 2.1 (1.1-3.7) 3.0 (2.0-4.5)

0.84 0.92 0.77 0.84 0.79 0.82 0.83 0.90

1.7 (1.2-2.4) 2.9 (1.8-4.9) 1.6 (1.1-2.4) 1.7 (1.1- 2.4) 1.9 (1.2-2.9) 2.0 (1.5-2.8) 2.8 (1.6-4.9) 3.0 (2.1-4.2)

Hip fractures

“Ageand BMI adjusted. It is the first time that a site such as the spine could be measured by a QUS technique, and the results appear to be promising. All other measured sites showed highly significant discrimination between cases and controls except the,spine. Although this is a protorype, the conclusions obtained demonstrate the encouraging potential of multiple-site ultrasonic measurements.

Can Ultrasound Determine Bone Structure? A Clinical Study of Patents with Renal Failure Requiring Dialysis S Patel, J Kwan, G McGee, G Thomas, and D Johnson

Department of Rheumatology and South West Thames Renal Unit, St. Helier Hospital, Surrey, UK Quantitative ultrasound (QUS) measures bone mineral density (BMD) and is possibly influenced by other variables such as bone structure. Therefore, QUS may potentially have a role in the assessment of bone structure in certain metabolic bone diseases such as renal osteodystrophy (ROD), which is heterogeneous in both bone density and structure. The objectives of this study were to see if QUS could detect differences between different types of ROD and assess whether bone structure was more important than bone density to QUS measurements. The authors recruited 64 patients, 33 treated with hernodialysis (HD) and 31 with chronic ambulatory peritoneal dialysis (CAPD). Patient details were obtained by questionnaire and review of medical notes. Ultrasound measurements were carried out using a LunarAchilles Plus ultrasound densitometer.The authors hypothesizedthat ifbone densitywas the major influenceon QUS, there would be a positive linear relationshipbetween QUS and serum parathyroid hormone levels (PTH). If, however, structurewas the predominant influence, then a quadratic relationshipwould be expected. Stiffness Z scores for all patients were significantly lower than normal (-0.55, p < O.O1), and Z scores were s@cantly higher in CAPD compared to H D patients (-0.21 and -0.86, respectivelyp = < 0.05). This difference could not be explained by age, sex ratio, physical activity, or duration of renal failure, which were similar in both dialysis modalities. Weak positive linear correlation was found between serum PTH and QUS parameters, with SOS being statistically significant ( r = 0.28; p < 0.05). The authors concluded that QUS is influenced predominantly by trabecular BMD rather than structure. By using QUS, it was confirmed that BMD increases with PTH in dialysis patients-a relationship that has previously been demonstrated, using quantitative computerized tomography of the spine. The findings do not support a role for current transmission ultrasound techniques for the assessment of bone structure in dialysis patients.

Journal of Clinical Densitornetry

Volume 1, Number 1

Spring 1998

The Utility of Rapid Heel Ultrasound Measurements for Genetic Studies in Russian-Jewish Immigrants PJ Rackoff, D Barile, C Patton, CR Kessenich, J Trempe, and CJ Rosen Beth Israel Medical Center, New York, NY and St, Joseph Hospital, Bangor, ME Osteoporosis is a disease characterized by structural changes in the property and density of bone. Because there is a strong heritable component to the acquisition of bone mineral density (BMD), and bone mass is easily measured by dual X-ray absorptiometry (DXA), BMD by DXA is considered the best phenotype for studying genetic determinants of this polygenic disease. Recently, BUA of the calcaneus by ultrasound (US) has been shown to be an independent predictor of hip fractures. Since US is portable, inexpensive, and accurate, the authors postulated that the stiffness index (SI) of the calcaneus (CA) could be a suitable phenotype for studying inheritability of osteoporosis in large cohorts, sib-pairs, and family pedigrees. To test this hypothesis, the authors performed a pilot study of Russian-Jewish immigrants in Washington Heights, NY.They recruited by mail, phone, and leaflet, healthy mother-daughter pairs for heel US. The authors also collected DNA for genotyping and serum for three candidate hormones (IGF-I, 25 hydroxyvitamin D, and parathyroid hormone). Initially, 15 mother-daughter pairs were studied with the Achilles+ (Lunar, Madison, WI) using 1 min survey(5') and 3 min (0modes repeated twice. The stiffnessindex was reported as SI. The mean age of the mothers (M) was 63.1 rt 1.8 yr, the mean age of the daughters (D) was 35.5 k 1.6 yr. S and C measurments correlated very closely: Y = 0.99, ? = 0.98, p < 0.0001. The standard deviation of the residuals was 2.0. The coefficient ofvariation (cv)for Sand C modes were not different.The precision error of the S mode was 1.3% for M and 2.1% for D. Mean SI for M was 77.8 f 4.3 ( T = -1.4) and for D was 93.2 f 2.8(T= -0.5) The correlation between M and D for SI was Y = 0 . 2 5 ; ~ = 0.15. In summary, one minute US scans are reproducible and accurate; healthy postmenopausal Russian-Jewishwomen have low SI and are at high risk for osteoporotic fractures; and there is a heritable component to SI which should permit further phenotypic characterization of larger cohorts. In conclusion, the authors believe that 1-min heel US scans will be useful for large-scale studies to determine those heritable factors that regulate the osteoporosis phenotype.

Quantitative Ultrasound Measurements of the Finger Phalanges in Rheumatoid Arthritis: New Sites and New Parameters P Roben, R Barkmann, and CC Gluer OsteoporosediagnostikKiel, Klinik fur Radiologische Diagnostik, CAU Kiel, Germany Preliminary reports have indicated that Quantitative Ultrasound (QUS) measurements at the finger phalanges may be useful to detect changes in the joints affected by rheumatoid arthritis (RA). The authors extended the standard measurement at the distal metaphysis of the proximal phalanx by additional measurements through the PIP joint and calculated several new parameters from the ultrasound signal in addition to the standard value amplitude dependent speed of sound (AD-SOS). Seventeen patients with R4 (25-69 yr, mean 54.7 f 14.6; 4 men, 13 women) and 21 age-matched control patients with vasculitis (26-68 yr, mean 53.5 f 13.4; 7 men, 14 women) were measured. Illness was present for at least 6 mo before the investigation. Measurements were carried out using the IGEA DBM Sonic 1200. The authors used a special, low sensitivity trigger-adapted research instrument to observe a wider time window of the US signal. New parameters were investigated: broadband ultrasound attenuation (BUA) (0.8-1.2 MHz) calculated from the first two periods of the US signal, adjusted to the signal transmitted through water, AUFW; area under the bone-specific first part (fast wave) of the US signal; W, width of the fast wave. For the standard measurement procedure, one hand was measured twice. Both index fingers were investigated at the point twice (US transmitted in dorso-volar direction through the joint gap of the index finger). For statistical analysis, the mean values were calculated. Additionally, precision was determined separately by investigating 10 healthy volunteers. T-tests assuming unequal variances (Welch Anova t-test) were performed. The standard measurement procedure allowed to discriminate between the two groups but measurement at the PIP joint showed even better performance.

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Abstracts

These first findings indicate that at QUS of the PIP joint may be useful to assess the presence and perhaps severity of a fracture. Speed of sound and BUA seem to be most promising in this respect.

Salisbury Normative Database for the Mccue Ultrasound Bone Densitometer JC Robertson,' GE Kempson,' C Osmond,2 A Could, and S Venkatachalam' 'Department of Rheumatology, Salisbury District Hospital and 2MedicalResearch Council Epidemiology Unit, Southampton General Hospital Recent research (1) has documented that ultrasound bone density measurements of the 0s calcis can predict the risk of hip fracture as well as DEXA scans of the hip itself. The McCue ultrasound bone densitometer measures the density of bone in the 0 s calcis using gel-coupled transducers. The MKII version is currently in use in Salisbury District Hospital. The authors have established a normative database for normal volunteers from five institutions and four GP practices in Salisbury. Moderate exclusion criteria similar to those used to construct the original database were used. A total of 1207 volunteers were measures in he age range from 18-86 yr. At the present time, the databases is limited to females. Both normalized broadband ultrasound attenuation (nBUA) and velocity of sound (VOS) increased with age and the rate increases around the age of 50 yr. Current analysis by the manufacturers show similarity between the Salisbury database and the original version. References

1. StewartA, Reid DM, Porter RW. 1994 Broadband ultrasound attenuation and dual energy X-ray absorptiometry in patients with hip fractures. Which technique discriminates fracture risk. Calcif. Tissue Int. 54:466-469.

Heel Ultrasound Reference Data for Caucasian Women in the USA C Rosen, M McClung, M Ettinger, C Gallagher, D Baldwin, K Faulkner, J Trempe, and C Miller Comparison of patient results to an accurate reference population is necessary for proper clinical assessment. The authors measured the 0s calcis using ultrasonometry (Achilles+,Lunar Corp., Madison, WI) to establish young adult and age-matched reference data for Caucasian women in the United States. They also determined the standard deviation in order to compute T and Z scores. Seven hundred thirty-four women from four geographically distinct regions of the USA (Oregon, Nebraska, Florida, and Maine) were studied. Two hundred ninety-two young adult Caucasian women ages 20-39 yr and 442 Caucasian women age 40-79 yr (average 111 subjectddecade) were recruited in a randomized fashion to minimize bias. All subjects gave informed consent and received one measurement of their heel stiffness. Data from the five centers did not differ significantly by geographic site and were pooled into a single data set.

Stiffness Values by Decade Age range, yr

Mean

S.D.

20-29 30-39 40-49 50-59 60-69

99.6 98.4

15.8 15.8 16.9

70-79

97.0

86 5 73.8 69.9

17.1

12.6 13.0

Stiffness, the combination of BUA and SOS, had a mean value of .99 in one young adult population. Analysis of the data showed the young adult group was best defined at age 20-35 yr, since stiffness began a significant decline after age 35. The stiffness data, expressed as a percentage of young adults, were consistent with DEXA data for spine and hip (i.e., a 25-30% postmenopausal decrease). This study represents one of the first comprehensive randomized examinations of ultrasound stiffness in the US population. Since T scores for each postmeopausal decade also were consistent with DEXAT scores, there is potential for applying WHO criteria to ultrasound results.

Short-Term Phantom Reproducibility in the Concordant and ParisTMBone Ultrasound Densitometers RG Saade' and TV Sanchez* 'McGill University, Montreal, Canada; and 2NorlandMedical Systems, Fort Atkinson,

WI

The Concordant and Parism bone ultrasound densitometerswere used in a short-term reproducibility study using four different phantoms. Velocity of sound (VOS),broadband ultrasound attenuation (BUA), and temperature were measured.

journal of Clinical Densitornetry

Volume 1, Number 1

Spring 1998

Coefficients of variation (CV%) and standard deviation (SD) were calculated for VOS (ms') and BUA (db MHz') across the four Phantoms (Ph) in both densitometers, and are given in the following table (C = Concordant; P = Paris). ~~

Ph 1 2 3 4

vos- c 0.04 0.24 0.03 0.03

vos-P

(0.76) (3.33) (0.47) (0.51)

BUA-C

0.03 (0.5) 0.05 (0.78) 0.04 (0.66) 0.0 (0.0)

0.75 (0.81) 2.19 (1.98) 1.42 (1.47) 1.88 (1.85)

~~

BUA-P 0.8 (0.3) 1.28 (1.3) 0.93 (1.02) 0.75 (0.79)

Both densitometers show good reproducibility results. The CV(%) obtained from Paris is significantly less than that of the Concordant for both VOS and BUA (Jee table below). [CV (Concordant) - CV (PariP)]/CV (Concordant)

P

For VOS (%)

For BUA (%)

25 79 -25 100

-7 42 34 60

Calibration of BUA and VOS in the Concordant Ultrasound Densitometer by a Calibration Phantom Tv Sanchez,' RG Saddat,' TW Mackey,' and L Harrold'

'Norland Medical Systems, Fort Atkinson, Wl; and ZMcGillUniversitK Montreal, Quebec, Canada Calibration of ultrasound densitometers to a fixed calibration phantom allows the scanner to be fixed to known values and field-tested to ensure proper operation. The authors have evaluated two of the origianl Concordant Ultrasound Densitometers against a primary calibration phantom to define VOS (m/s) and BUA (dB/MHz) calibration curves for the scanners. Two Concordant scanners each evaluated a primary phantom seven times at 12 VOS factors between 1.1 and 0.97, and seven times each at eight BUA factors between 0.975 and 1.005. Results in the two scanners did not differ from each other. Precisions for VOS and BUA in the VOS-factor studies averaged 0.016 and 0.393%, respectively. Precisions for VOS and BUA in the BUA-factor studies averaged 0.006 and 0.328%, respectively. Significant correlations were seen in regressions of VOS to the VOS factor and BUA to the BUA-factor. Correlations are shown below.

VOS factor BUA factor

vos

BUA

0.9997 -0.0883

0.0825 0.8528

Results show that the VOS factor and BUA factor can be used to adjust a scanner to produce a specific VOS or BUA result. These calibration factors combined with the use of phantoms with fixed known values will allow operators to adjust their scanner to generate consistent known results for VOS and BUA over time.

Quantitative Ultrasound Measurements: Short- and Long-Term Precision KE Sherwood, BM Ingie, and R Eastell

Bone Research Group, Division of Clinical Sciences, University of Sheffield, UK Coefficient of variation (CV) as a measure of precision is not appropriate for ultrasound measurements because it does not take into account the different range of measurement values. Index of individuality (101) adjusts the CV for the measurement range. The authors aimed to estimate the I 0 1 in a short-term precision study to compare the short-term (st) and long-term (It) precision of the Lunar Achilles+, Hologic Sahara, CUBA Clinical (calcaneus), and DBM Sonic (finger) ultrasound machines. They made duplicate measurements on 70 women (ages 2145 yr, mean 33.4 yr) to calculate short-term CV and population CV. Five healthy women (ages 29-44 yr) were

Abstracts measured once a week for 52 wk to calculate long-term CV (LCV). Results were expressed as CV. The authors then calculated the I01 as (stCV) or (ItCV)/population CV x 100. A low I01 indicates good precision relative to the reference range. Short term Ultrasound Machine

cv, Yo

Achilles + SOS Sahara SOS CUBA VOS DBM Sonic AD-SOS Achilles + BUA Sahara BUA CUBA BUA Achilles + Stiffness Sahara QUI

0.23 0.21 0.30 0.53 1.51 2.01 4.13 1.45 1.31

Short term

Long term

101, %

cv,%

Long term 101, Yo

13.0 12.8 16.4 22.8 19.1 11.6 19.1 11.1 8.1

0.65 0.54 1.15 0.99 0.90 3.96 6.04 4.16 3.58

36.6 32.9 63.0 43.1 11.5 22.3 28.1 31.7 23.4

Long-term CV and I01 are greater than short-term CV and 101, especially for velocity measurements (SOS, VOS). Achilles + stiffness and Sahara QUI have the best stIOI, but not 1tIOI. The BUA measurements have the best 101, reflecting the greater stability of this measurement in the long term.

Short- and Long-Term Precision in Three Quantitative Ultrasound (QUS) Scanners in Normal Men, Women, and Osteoporotic Women A Stewart and DM Reid

Department of Medicine and Therapeutics, University of Aberdeen, UK Quantitative ultrasound (QUS) measurements of bone have been shown to be independent predictors of osteoporotic fracture risk. Drawbacks of this technique in the past have included the precision of the scanners, which is said to be poorer than dual energyX-ray absorptiometry (DXA). In this study, the authors compared three scanners (McCue CUBA Clinical, Lunar Achilles+, and Osteometer DTU-One imaging scanner). Short- and long-term precision was calculated in vitro using the phantom supplied by each manufacturer measured 10 times in succession and over a 6-mo period. The short term standardized coefficients of variation (SCV%) were as follows: BUA McCue 0.9%, BUA DTU-One 1.42%, BUA Lunar 0.55%, VOS McCue 2.74%, VOS DTU-One 2.12%, VOS Lunar 2.34%, and stiffness Lunar 1.39%. In vivo precision (SCV%) was calculated in 19 normal females aged 25-57 yr and the results are as follows: for BUA McCue 2.87%, BUA DTU-One 2.82%, VOS McCue 2.99%, VOS DTU-One 2.55%, BUA Lunar 2.45%, VOS Lunar 1.45%, and stiffness Lunar 1.73%. Precision was also calculated in 10 normal men and 20 osteoporotic women with similar results. In conclusion, the Lunar Achilles+ scanner is more precise for BUA, while the Osteometer DTU-One is more precise for VOS in vitro. When comparing different manufacturers, the SCV should always be used, since there is a large discrepancy in the dynamic ranges of normal values derived by each scanner. Unlike DXA, precision is no worse in osteoporotic women than “normals.”

Influence of Bone Tissue Density and Elasticity on Ultrasound Propagation: An In Vitro Study F de Terlizzi,’ 5 Battista,’ A Doratii,’ V. CaneI2and R Cadossi3 ’IGEA Biophysics Laboratory, Carpi (Modena), Italy; ZDepartment of Morphological and Medicolegal Sciences, University of Modena, Italy; and 3Department of Medical, Oncological, and Radiological Sciences, University of Modena, Italy Ultrasounds (US) are mechanical vibrations that, propagating in a medium (such as bone tissue), are used to study material properties. Ultrasound energy transmission in a material depends on density elasticity, and microstructure. In the present study, the authors evaluated how density and elasticity of trabecular bone tissue independently influence the transmission of 1.25-MHz US pulses. Twelve cylindricalspecimens (08 mm, height 5 mm), excised from pig phalanx epiphysis and inserted singularly in a closed circuit, were decalcified by 0.5 Methylenediamine tetra-acetic acid (EDTA), pH 8.0. For each specimen, during the decalcification,at d 0,2, and 7, the authors evaluated ultrasound transmission (velocity and signal pattern

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Journal of Clinical Densitometry

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analysis), density (weightlvolume), and elasticity (slope of the stress-strain regression line). Furthermore, to control the decalcification, at d 0, 2, and 7, transversal sections of sample specimens, enclosed in methacrylate, were microradiographed. The authors found a significant correlation between US velocity and bone density (? = 0.70) and between US velocity and elasticity r?= 0.59. When density and elasticity were considered together, the correlation with US velocity increased to 12= 0.84. It was then observed that, after adjusting the correlation by density, US velocity showed a poor correlation with elasticity (12 = 0.16), whereas the US pattern parameters remained highly correlated with elasticity: ultrasound peak amplitude r = 0.48 and peak slope r = 0.62. The authors data shows that US velocity is mainly dependent on bone density and that some US signal pattern characteristics are more representative of bone elasticity. These results may have important clinical implications, particularly for the discrimination of fractured and nonfractured subjects with identical bone mineral density.

A Prospective Study of Fracture Prediction Using Heel Ultrasound in Women 45-75 Years P Thompson, J Taylor, R Oliver, and A Fisher Osteoporosis Dorset, Shelley Road, Bournemouth, Dorset, UK

All women between 46 and 75 yr in two general practices were invited to participate. Heel QUS was measured at baseline and subsequent fractures identified during 3 yr. The QUS results were analyzed graphically after age adjustment and using Cox proportional regression to estimate odds ratios for fracture risk. Three thousand one hundred eighty women were scanned (79% of sample). Sixty-three wrist, 12 hip, 4 vertebral, 7 proximal humerus, 3 pelvic, and 61 other fractures were identified over a mean follow-up of 31 mo. There was a fivefold difference in numbers of wrist and osteoporosis-related fractures (hip, vertebra, pelvis, and humerus combined) between the lowest and highest quartiles of QUS results adjusted for age. The odds ratios/one standard deviation decline in QUS parameters adjusted for age were wrist fractures (BUA = 1.6, SOS = 1.5, stiffness = 1.7), osteoporosis-related fractures (BUA = 1.9, SOS = 1.6, stiffness = 2.0), and other fractures (BUA = 1.0, SOS = 1.1, stiffness = 1.0). When analyzed for each 10 yr age group, the odds ratios were higher in the 56-65 yr group than in the other decades. In women between 46 and 75 yr, heel QUS can predict wrist and osteoporosis-related fractures at about the same level that dual X-ray absorptiometry of one site can predict fractures at another site. This extends the current literature to include fracture sites other than the hip in younger women.

Dexa and Ultrasound Measurements of Human Calcaneus In Vivo J Toyras,’,* H Kroger,3 and JS Jurvlin4 Departments of ‘Clinical Physiologx ZAnatomy, and 3Surgery, Kuopio University and Kuopio University Hospital, Kuopio, Finland The aim of this study was to investigate interrelationships between bone mineral density and bone ultrasound (US) parameters of the calcaneus in vivo. The authors were particularly interested in the effect of calcaneal size and site of the measurement on ultrasound results. Calcaneal bone of 34 healthy women (aged 20-52 yr) were studied using a Lunar Achilles Plus ultrasound device. Broadband ultrasound attenuation (BUA, dB/MHz) and speed of sound (SOS, m/s) in calcaneus were determined. After US measurements, exactly the same area of the heel was examined with a Lunar Expert DEXA-device, and bone mineral density (BMD, g/cm*) was determined. The width of the heel at the site of analysis was measured using a micrometer. Significant positive correlation between US parameters and BMD was found (BUA vs BMD, I = 0.668, n = 34; SOS vs BMD, I = 0.611, n = 34). While BUA showed no significant correlation with the heel width, negative correlation ( r = 0.350, n = 34) was demonstrated between SOS and heel width. The results revealed that SOS decreased as patient’s body mass index (BMI) increased ( I = 0.565, n = 34). Also, heel width and BMI were positively correlated ( I = 0.399, n = 34). DEXA images revealed that, as BMI increased, the probability that US beam partly passed the calcaneus also increased. In the worst case, only 52% of the beam hit the bone. Based on this in vivo study, BUA and SOS predict only moderate BMD in calcaneus. In US measurements, soft tissue layer, especially fat over the calcaneus, may induce uncertainty for the measurements. While the micrometer measurements of the heel width also included soft tissue thickness, it is probable that the negative correlation between SOS and heel width or patient BMI arises from the effect of variable soft tissue thickness over the calcaneus.

111

Abstracts

Bone Strength as Estimated by Dexa and Ultrasound Measurements In Vitro J Toyras,',*P Valanta? H Kroger,4and JS Jurvelin'

Departments of 'Clinical PhysiologH 2Anatomy,3Applied Physics, and 4Surgery,Kuopio University and Kuopio University Hospital, Kuopio, Finland In this study, the authors estimated bone strength using dual energy X-ray absorptiometry (DEXA) and ultrasound (US) measurements in vitro. Young adult cows ( n = 19) were used to obtain trabecular bone blocks ( n = 56) from the proximal and distal femur and from the proximal tibia. The samples were analyzed using Lunar Achilles Plus to obtain broadband ultrasound attenuation (BUA), speed of sound (SOS), and stiffness values. In a series of samples (n = 6 ) , measurements were repeated after gradual reduction of bone thickness (40 mm + 5 mm). The site of US analysis was scanned using Lunar Expert to quantitate areal bone mineral density (BMD, g/cm3). By measuring the bone thickness, volumetric BMD (g/cm3)was obtained. Physical (wet) density of the samples was measured using Archimedes' principle. The samples were destructively tested in compression to obtain Young's modulus and ultimate strength. Finally, the true mineral density was determined by ashing. When examining effects of bone size, only volumetric BMD (g/cm3) was independent of size. SOS showed linear positive relation with the sample thickness. BUA-thicknessrelation could be described accuratelywith a 2-order polynomial fit. Best-fit equations were used to eliminate the bone size effect on US-parameters. Relatively high BMD-strength (Y = 0.869, n = 53) and SOS-strength (Y = 0.738, n = 50) correlationswere found. However, BUA showed no significant correlation with Young's modulus or ultimate strength. Systematically, size-corrected DEXA or US parameters showed higher correlation with mechanical properties than uncorrected parameters. When physical density and SOS were combined (pg), the highest correlation (I = 0.939, n = 45) was found with ultimate strength. Using the parameter BMD * (SOS)', obtainable from combined DEXA and US analyses, correlation coeffcient (Y = 0.888, n = 45) with ultimate strength was higher than that calculated between strength and DEXA or US parameters alone. The author's results indicate that both DEXA and US parameters depend on the bovine bone size. It is proposed that, possibly, an instrument combining both US and DEXA measurements could improve accuracy of the clinical analysis of bone strength. However, the findings should also be verified using human bone.

Calcaneal Ultrasound Imaging: Influence of Various Regions of Interest on Precision JPW van den Bergh, I Hommel, ARMM Hermus, J Thijssen, and AGH Smals

Department of Endocrinology, Academic Hospital Nijmegen, Netherlands The influence of various regions of interest (ROI) on precision in calcaneus ultrasound parametric imaging was evaluated using the UBIS 3000 ultrasound device. The authors compared the precision of broadband ultrasonic attenuation (BUA) and speed of sound (SOS), by five consecutive measurements with interim repositioning in 30 healthy subjects (23 female, 7 male, mean age = 43 yr). Three different methods were used: automatic ROI (ROI-A), using an algorithm described by Fournier, which is defined as the circular region of lowest attenuation in the posterior tuberosity of the calcaneus; copied ROI (ROI-C), using a copy of the calceanus contour of the first measurement to define the same anatomical ROI in the other four measurements; and fKed ROI (ROI-F), with fixed coordinates of ROI relative to the footplate, mimicking the approach of ultrasound devices with fixed transducers. The size of the circular ROI was varied between 8 and 20 mm to evaluate its effect on precision. Precision is defined as the standardized CV (= CV% of group/(5-95% range/mean of group). The results are summarized in this table. ROI-A SCV-8 mm SCV-10 mm SCV-12 mm SCV-14 mm SCV-16 mm SCV-18 mm SCV-20 mm

ROI-C

ROI-F

BUA

sos

BUA

sos

BUA

sos

2,26 2,19 2,58 225 2,46 2,58 233

4,54 4,53 5,37 4,5 1 4,46 4,73 4,77

2,77 2,59 2,83 2,31 2,52 2,72 2,92

443 4,42 5,85 4,40 4,39 4,37 4,5 1

4,46 4,04 3,69 3,24 2,88 2,85 3,11

465 4,73 4,67 4,73 4,84 5,20 538

The 14-mm ROI gives the best SCV for BUA and SOS measurements. There is little difference between the CV of automatic and copied 14-mm ROI. This could be important for longitudinal studies, because the region of lowest attenuation might shift to an anatomically different region with time. With the copy technique, it is possible to evaluate longitudinal changes of BUA and SOS in the same location of the calcaneus, independent of changes in the location of the lowest attenuation. Although short-term precision is best with an automatic ROI of 14 mm, it is not known how longitudinal changes can be best monitored using calcaneal ultrasound.

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Spring 1998

Interpretational Reference Data: Ranges for the Sahara Clinical Bone Sonometer

’

’

E von Stetten,’ KE Wilson, H Ouellet, D Schoenfeld, P Steiger, and JA Stein’ ‘Hologic, Inc., Waltham, MA; and 2Boston Biostatistics, Inc., Framingham, M A

Reference ranges are critical to the clinical use of any diagnostic instrument, and are particularly important for heel ultrasound systems due to the growing international acceptance of ultrasound and the potential for widespread use in the general clinical community. Recently, however, there has been considerable debate over the definition of appropriate methods for subject selection and data analysis in reference data studies. This multicenter international study was designed to acquire extensive heel ultrasound reference data for female subjects from a number of different countries, and to test the sensitivity of the results to inclusion/exclusion criteria and analysis methods. Heel ultrasound measurements were obtained for Caucasian female subjects recruited in seven countries using the Hologic Sahara Clinical Bone Sonometer. For each country, the study was designed to be large enough for a statistically significant assessment of the effects of inclusion/exclusion criteria and analysis methods, and to minimize the possibility of geographic or recruitment bias. Biographical data and information regarding medications and dosage conditions that may affect bone metabolism were obtained from each subject. Data were analyzed with a number of different statistical models, and the effect of inclusion/exclusion criteria was assessed. Sahara ultrasound parameters were formed to decline with age, and the age dependence was best described by decade-specificmean values. Linear and polynomial fits were found to deviate significantly from the decade means. Population SD values for all parameters varied only minimally with age. While results for subjects with specific conditions or medications, deviated from those for the entire population, the net effect of including subjects with all conditions and medications was found to be negligibly small. In conclusion, Sahara reference ranges were generated for Caucasian females from seven countries. Inclusion of subjects with conditions or on therapies which could affect bone metabolism had an insignificant effect on results. Final reference ranges were based on all subjects enrolled, and apply to the Caucasian female population of each country as a whole.

Ultrasound Bone Profile Score (UBPS) and Transmission Speed of the Phalanges in Osteoporosis and Patients on Glucocorticoids Chr. Wuster, ’ T Soballa,’ J Schlege,’ JR Cadossi,z R I ~ a n i P, ~Heilunann,’ and R Zieglerl ‘Internal Medicine, University o f Heidelberg; 2University of Modena; and 31GEA, Carpi, Italy

The distal metaphysis of the first phalanx of the fingers 11-V is, like the vertebral body, a useful site for the measurement of bone density and structure. With an ultrasound device (DBM Sonic 1200, IGEA, Italy), we measured the amplitude dependent speed of sound (adSOS) and the ultrasound bone profile score (UBPS), a score that is calculated from the graphic traces of the receiving probe at phalanges 11-IV, as well as bone mineral density (BMD) at the lumbar spine using dual X-ray absorptiometry (DXA). Precision of the measurements was as follows: short-time CV% = 0.9, long-time CV% = 1.8, SCV% = 5.9, and RMSSD% = 1.8. The validity of adSOS and UBPS was examined in 5 1 healthy men and women (mean age 36 f 5 yr), 38 patients with osteoporosis and vertebral fractures (mean age 58 f 11 yr), and 34 patients on glucocorticoid (GC) treatment (>7.5 mg prednisone for 6-12 mo) (mean age 49 f 14 yr). Ultrasound bone profile score and adSOS significantly discriminated healthy controls from patients with osteoporosis or patients on G C treatment ( p c 0.00001). Dual X-ray absorptiometry significantly discriminated healthy controls from patients with osteoporosis, but could not significantly discriminate between healthy controls and patients on G C treatment. The areas under the ROC curves were 0.96 (adSOS), 0.99 (UBPS), and 0.89 (DXA) for patients wihh osteoporosis and 0.79 (adSOS), 0.80 (UBPS), and 0.55 (DXA) for patients on G C treatment. These results show that adSOS and UBPS are precise parameters to measure loss of bone mass and/or structure. The detection level of pathological changes in osteoporosis are similar between adSOS and lumbar BMD (DXA), and discrimination is improved by using the UBPS. This might be explained by the detection of more structural deterioration in bone by the UBPS, rather than changes in bone mineral alone. The authors conclude from this study that ultrasound of phalanges can be used in patients with fractures equally well as DXA. In patients on G C treatment, QUS might be advantageous in comparison to DXA.

113

Abstracts Comparison of In Vivo and In Vitro Examinations of Phalanges of Human Cadavers Using Ultrasonometry Chr. Wuster,' St. Becker,' P Heilmann,' F de Terlizzi,2R Cadossi,) and R Ziegler'

'Internal Medicine, University of Heidelberg; zIGEA, Italy; and 3Universityof Modena, Italy Quantitative ultrasonometry (QUS) is widely used to determine future osteoporosis fracture risk in postmenopausal women and elderly men. There is equal amount of prospective clinical data for ultrasound as there is for the radiological devices. However, the interobserver variance using the system measuring the amplitude dependent speed of sound (adSOS) at the phalanges (DBM Sonic 1200, IGEA, Carpi, Italy) needs to be improved. Therefore, the authors conducted a study of 26 human cadavers (14 females, 12 males) with a mean age of 82 yr in females and 76 yr in males. They measured adSOS in vivo at phalanges 11-V of both hands and the same again in a water bath after removal of soft tissue. Bone mineral density (BMD) using dual X-ray absorptiometry (DXA) (Hologic QDR 1000) was measured in the phalanges, the lumbar vertebra L3, and the hips of each cadaver. There was a highly significant positive linear correlation between adSOS and BMD of the phalanges in vitro ( r = 0.658) and in vivo ( r = 0.647). There was no significant correlation between adSOS or DXA of the phalanges and BMD of L3 or the hips. Ultrasound measurements of the phalanges in vitro at different rotational angles showed best results at a horizontal direction and 90", but not at 45 and 135". Correlation coefficients (9) were 0.64,0.54,0.37, and 0.52, respectively,There was no correlation between 0 and 45" except at the middle finger, which was probably a result of the particular shape of the small phalanges. This study showed that ultrasound measurements at the phalanges are highly independent of soft tissue. The high correlation between QUS and DXA at the phalanges indicates that BMD has a major influence on QUS measurements. However, the rotational differences might be explained by the influence of structural properties of the bones on QUS and may be responsible for the lower interobserver precision in vivo. Future studies should investigate the influence of structural components as measured by FQCT and biomechanical testing on QUS.

Ultrasonographyat the Phalanxes: Analysis of a 10,677 European Woman Database Chr. Wuster, R Cadossi,25. Battista,) and R Isani3 Depafiment of Internal Medicine I, Endocrinology and Metabolism, University of Heidelberg, Germany; ZDepartmentof Medical, Radiological and OncologicalSciences, Universiiy of Modena, Itak and 31GEA,Carpi, Italy The use of ultrasound (US) at the phalanxes of the hand to assess bone quality has been investigated by a number of researchersthroughout Europe. The results of ultrasonography measurements at the phalanxes performed on 10,677 women have been used to create a large database. The ages of subjects ranged from 2 mo to 100 yr: 978 subjects up to 18 yr, 3316 in premenopause, and 6383 in postmenopause. Four hundred ninety-five women had documented osteoporotic fractures. All subjects had been measured by DBM-Sonic 1200 (IGEA, Italy), two parameters had been recorded: amplitude dependent speed of sound (AD-SoS, mls) and ultrasound bone profile score (UBPS, U from 1-100). This figure shows the age-related changes of AD-SoS in nonfractured subjects. I

Both ultrasonography parameters, AD-SoS and UBPS, discriminate between age-matched fractured (495)and nonfractured (266) subjects: p < 0.001 andp < 0.005, respectively. The data collected show that ultrasonography at the phalanxes is highly sensitive to aging and can be used to identify subjects with osteoporotic fractures.