Calcif Tissue Int (1992) 51:180--183

Calcified Tissue International 9 1992 Spdnger-Verlag New York Inc.

Ultrasound Attenuation of the Calcaneus in the Female Population: Normative Data John E. Damilakis, 1 E m m a n u e l Dretakis, z and Nicholas C. Gourtsoyiannis 3 Departments of 1Medical Physics, 2Orthopaedics and Tranmatology, and 3Radiology, University of Crete, Medical School, Stavrakia Iraklion, Crete, Greece Received February 6, 1992

Summary. Broadband ultrasound attenuation (BUA) on the os calcis has been proposed as a safe and reliable technique for evaluating skeleted status. The present study provides preliminary normative BUA results on 93 female subjects divided into five age groups. These data can be used as a guide for comparing the results of individual studies. The diagnosis of osteoporosis was determined from lateral calcaneus and spine radiographs. Postmenopausal osteoporotic female subjects had significantly lower BUA values than normal women (P < 0.001). There was a significant negative linear relationship between BUA and age in the postmenopausal subjects. No correlation was found between body size parameters (weight, height, and body mass index) and ultrasound attenuation. These results indicate that BUA may be a useful technique for detection of persons at risk. Key words: Osteoporosis - Bone density - Ultrasound.

Materials and Methods Subjects One hundred and fourteen healthy asymptomatic female Caucasian subjects with no previous atraumatic fractures were included in the study. They were assessed by medical history and physical examination for eligibility for the ultrasonic study. Sixteen subjects were excluded because they had symptoms associated with diseases or conditions known to affect bone, such as diabetes mellitus, Paget's disease, rheumatoid arthritis, pregnancy, immobilization, or obesity (body mass index >30 kg/m2). Bone ultrasonic attenuation values of the calcaneus were determined in 98 female subjects who ranged in age from 25 to 87 years. Details of height, weight, age and menopausal status were recorded for each subject. Each subject had a lateral calcaneus radiograph taken. In most subjects, lateral spine radiographs were also taken for additional information concerning bone status. A woman was classified as normal or osteoporotic according to changes in the trabecular pattern of the calcaneus with age [10] and to atraumatic vertebral body fractures as they were observed radiologically. Jhamaria et al. [10] have divided the progressive loss of compression and tensile trabeculae of the calcaneus into five grades: from that in the normal healthy adults (grade V) to that in severe osteoporosis (grade I). This method correlates significantly with Singh's index [10] and with bone density [11]. The images were evaluated blindly by two investigators without reference to the BUA values. In five subjects, the observers disagreed about the diagnosis, hence these ambiguous cases were excluded from the study. Table 1 shows the characteristics of the 93 subjects included in the study.

Over the last 20 years, several methods have been developed for quantitatively assessing bone mass and monitoring bone response to therapy. The techniques currently used are single photon absorptiometry (SPA), dual photon absorptiometry (DPA), dual energy X-ray absorptiometry (DEXA) and quantitative computed tomography (QCT). All the above methods utilize ionizing radiation. They are based on the concept of measuring photon attenuation in bones and converting the measurement into an equivalent of bone mineral density [1]. Techniques using nonionizing radiation included broadband ultrasonic attenuation (BUA) and bone velocity. In the BUA method [2], a short burst of ultrasound (US) is produced and the attenuation by the os calcis is measured. In the apparent velocity of ultrasound (AVU) [3], the velocity of US [V = (Kp )v2, w h e r e p i s mass density and K a constant representing bone quality] is measured in the patella. Bone strength is influenced by both the density and bone architecture [4, 5]. US methods have the advantage of providing information not only about density but complementary about bone structure [6, 7]. Recent studies have demonstrated the ability of the BUA technique to predict axial bone mass and differentiate normal from osteoporotic women [8, 9]. However, a range of normal BUA values has not been available. The aim of the present study was to establish a range of BUA values from both healthy and osteoporotic female subjects over a large age range.

Data Analysis

Offprint requests to: J. E. Damilakis

Data are presented as means -+ standard deviation (~ --- SD). Groups were compared statistically with the Student's t test; P values >0.05 were considered to be insignificant. Linear regression analysis was

Ultrasound Measurement The US attenuation measurement was performed in our subjects by means of a computer-controlled bone analyzer UBA-575 (Walker Sonix, USA). The system consisted of a water tank containing two broadband ultrasonic transducers, one acting as transmitter, the other as receiver. At the beginning of each patient scan, a "reference signal" is obtained at a number of frequencies (200--600 kHz) through water. Then the foot is positioned in the water bath and the ultrasonic transducers scan the calcaneus region in 1.6 mm increment. The computer compares the signal obtained by this scan with the reference signal and the difference between these two gives the frequency dependency of attenuation in the calcaneus. The slope of the attenuation-frequency curve is expressed in dB/MHz and is referred to as the BUA value.

J. E. Damilakis et al.: Ultrasound Attenuation of the Calcaneus Table 1. Characteristics of study population Age (year) 25-40 41-50 51-60 61--70 71-87

n 13 24 26 19 11

Weight (kg) 69 64 64 67 64

• 12 • 12 --_ 8 - 13 _+ 11

Height (m) 1.61 • 0.07 1.52 • 0.05 1.57 • 0.04 1.56 --- 0.07 1.52 _+ 0.07

BMI (kg/mz) 26.5 27.6 26.0 27.5 27.6

--- 4 --- 7 - 3 • 5 • 5

Abbreviations: n = number of subjects, BMI = body mass index

used to determine the relationship between variables. Multiple regression was used to estimate the simultaneous effect of many variables on BUA.

Results Short-term reproducibility was assessed in five female subjects by recording five successive independent measurements in each subject. The coefficient of variation (CV) was 3.8 -+ 1.4% (Table 2). All subjects were divided into two groups according to bone mass status: the normal group comprised of 74 normal subjects contained 31 premenopausal and 43 postmenopausal women. The osteoporotic group comprised of 19 osteoporotic subjects, all of whom were postmenopausal. Table 3 shows the B U A data for normal and osteoporotic subjects divided in five age groups. Individuals with osteoporosis had significantly lower B U A mean values than normal subjects in every group (P < 0.001). In Figure 1, B U A values of normal and osteoporotic women are given with respect to age. There is remarkably little overlap between osteoporotic and normal female subjects. The pooled mean --- SD of the normal postmenopausal and osteoporotic postmenopausal female subjects was 66.5 -+ 12 and 48.8 + 6, respectively. As the osteoporotic postmenopausal were 7 years older than the normal postmenopausal female subjects, one would expect lower mean BUA value of the osteoporotic group simply because of the age difference. Multiple regression analysis with independent variables the age and the osteoporosis status showed that the difference in the pooled mean B U A values is more disease related (P < 0.001) and less age related (0.01 < P < 0.05). As the age group 44-52 years included 14 premenopausal and 15 postmenopausal subjects, this group was studied further. The mean B U A of the premenopausal group was not significantly different from the mean of the postmenopausal group (P > 0.05). In order to investigate B U A as a function of age, we considered two populations: a premenopausal population that has no sudden changes in bone mass, and a postmenopausal population that suffers from rapid bone mass loss. The correlation between B U A and age was not significant (P > 0.05) in premenopausal women. By contrast, there was a significant negative correlation between B U A and age in both the postmenopausal normal subjects (r = - 0 . 3 5 , P < 0.05) and postmenopausal osteoporotic subjects (r = - 0 . 4 7 , P < 0.05). Multiple regression analysis with dependent variable the B U A and independent variables the body mass index, weight, height, and age was carried out. Only the age had a significant regression coefficient (P < 0.001) whereas the other variables had a nonsignificant regression coefficient.

181 Table 2. Five successive independent measurements of BUA in each of five normal female subjects Subject

BUA (dB/MHz) X - SD

1 2 3 4 5

67.4 --- 3.05 6l . 4 • 1.14 75.4. • 3.05 62.4 • 3.43 64.0 • 1.87

%CV 4.5 1.9 4.0 5.5 2.9 %CV (mean • SD) 3.8 • 1.4

Discussion The study of ultrasonic wave propagation in bone for the determination of bone mass in vivo has been reported since 1966 [12]. The ultrasonic attenuation in bone has been measured by Garcia et al. [13] and Barger [14]. The B U A technique was first introduced by Langton et al. [2]. They have carried out measurements of the frequency dependence of ultrasonic attenuation in the range 0.2-1 MHz in in vitro samples and in vivo os calcis heel bones. As a technique that is influenced not only by bone density but also by structural parameters, BUA will not necessarily correlate significantly with densitometric techniques. Nevertheless, a series of in vitro and in vivo comparisons of B U A technique and clinically used methods have been undertaken over the last years. BUA provides significant correlation with SPA and DPA [15-18], QCT [19-21], and D E X A measurements [22,

23]. Velocity of US in human bone in vivo was measured several years ago [24]. McCartney and Jeffcott [25] described an ultrasonic method that is based on measuring the time of ultrasonic flight for each of two pathways via the cortical shaft and through the central medulla of the equine third metacarpal bone. Sound transmission velocity was measured through the intact distal radius and ulna in newborns [26] with reproducible results. Osteoporotic bone fragility was detected by measuring apparent velocity of ultrasound (AVU) at the patella [3]. The Contact Ultrasonic Bone Analyser (CUBA) developed as a system that can provide both B U A and US velocity information [27]. The relationship between US measurements and incidence of fractures in the racehorse has recently been studied with C U B A [28]. This study provides, for the first time, values for B U A in both healthy female subjects and subjects with osteoporosis over a broad age range. B U A obtained from women suspected of having osteoporosis can be compared with these values. Our data for B U A in the 25--60 year groups were in accordance with those reported in normal subjects from the U S A ranging in age from 21 to 61 years [29]. Small differences may reflect geographical variations in bone status. Few other data are available for comparison; however, a recent study [8] has also revealed a decreased B U A of the os calcis in women with osteoporosis. The BUA average %CV for five subjects was 3.8% or 6.6% at a 95% confidence level (2 SD). If only two measurements are made with this average error, then one would have to observe a difference more than 9% in B U A to have confidence (95%) that the minimum detectable significant difference had occurred [30]. A bone loss of 3% per year, which is the average normal bone loss in early postmenopause [31], would therefore take 3 years to detect. In eight postmenopausal subjects in the age group 44-52 years, the period after

J. E. Damilakis et al.: Ultrasound Attenuation of the Calcaneus

182 Table 3. BUA data for 93 female subjects divided into five age groups Age (years) 25--40

41-50

n Normal group Prem. Postm. Osteoporotic group Prem. Postm.

2+-SD

13 0

n

71.6 --- 12.0 --

0 0

51-60 2•

11 13

---

SD

68.1 - 6.2 71.6 • 15.8

0 0

---

n

61-70 2•

7 16 0 3

n

69.9 -+ 11.4 64.9 • 12.0a -51.3 •

2.9

71-87 2+-SD

n

2•

0 9

-63.9 --- 5.8 a

0 5

-61.0 +- 5.73

0 10

-49.4 • 3.9

0 6

-41.8 • 6.1

Abbreviations: n = number of subjects, Prem. = premenopausal subjects, Postm. = postmenopausal subjects a p < 0.001 compared with osteoporotic women

12o

References

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Fig. 1. Age dependence of BUA for 93 subjects who underwent ultrasonic measurements. m e n o p a u s e was less than 3 years. B o n e loss may not be detected in these cases by the ultrasonic analyzer, which affects mean B U A value of p o s t m e n o p a u s a l w o m e n in this age group. This could be a possible explanation of the nonsignificant difference b e t w e e n the m e a n B U A of the postmenopausal and the p r e m e n o p a u s a l w o m e n in the age group 44-52 years. B U A is d e p e n d e n t on age but not on b o d y mass. H o w ever, it is k n o w n that there is a direct correlation b e t w e e n body weight and b o n e density in the os calcis [32]. As the heels carry the whole b o d y weight, it might h a v e been exp e c t e d that B U A and bone weight and body mass index would have a strong positive correlation. This did not p r o v e to be; we found positive but not statistically significant correlation. Possibly, scattering resulting from bone architecture of lean subjects is greater than that of obese. The simultaneous effect of absorption (density) and scattering on a t t e n u a t i o n m i g h t p r o v i d e similar B U A v a l u e s in b o t h groups. The non-ionizing nature of the m e t h o d allows multiple m e a s u r e m e n t s of the female population without the hazardous effects of radiation. In managing the care of w o m e n at menopause, b o n e ultrasonic m e a s u r e m e n t s can be recomm e n d e d as a m e t h o d for detection of high-risk population. Then, m o r e precise techniques can be used to monitor therapeutic t r e a t m e n t of osteoporosis or other diseases entailing bone demineralization. U n d o u b t e d l y , the use of the ultrasonic attenuation m e t h o d for screening of osteoporosis justitles serious consideration.

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