Acute and Subacute Changes in the Ultrasound Measurements of the Calcaneus Following Intense Exercise

The amount of exercise necessary to cause bone structural change in humans is unknown. We examined whether a single bout of intense exercise in vivo leads to acute and subacute changes in the physical properties of bone as measured by ultrasound. It was hypothesized that structural changes such as accumulation of fatigue microdamage would result in a decrease in velocity of sound (VOS) and broadband ultrasound attenuation (BUA) across the calcaneus. We performed a prospective cohort study in 111 (97 M, 14 F) entrants of the 1996 Melbourne marathon (42.3 km) and 28 (10 M, 18 F) nonrunning controls. Runners had a mean (SD) age of 45.3 ± 11.4 years (range 20–75), had completed 15.2 ± 17.3 prior marathons (0–88), and had been running regularly for 14.2 ± 9.2 years (0.25–50). An ultrasound densitometer (Cuba Clinical, McCue) was used to measure VOS and BUA across the right calcaneus. Runners were tested on three occasions: 1-3 days prior to, immediately after (<2 hours), and 5-6 days following the marathon. Seventy-three (66%) runners presented for all three measurements. Controls were tested on three occasions with the same time intervals as the runners. BUA values in the runners were significantly elevated by 5.0% immediately after the marathon but returned to baseline levels by the third test session (P= 0.0001). Changes in BUA values in the controls were not significant and all were less than 0.7% (P= 0.88). Age was a significant independent predictor of the BUA change between test 1 and test 2 in the runners (β= 0.2094; SE = 0.0917; P= 0.03). VOS measurements were not significantly different across the three testing sessions in both the runners (P= 0.07) and the controls (P= 0.33). Therefore, ultrasound measurements of BUA and VOS did not detect evidence of lasting structural change in the calcaneus following a marathon. Received: 15 July 1997 / Accepted: 11 May 1998     

Quantitative ultrasound imaging of the calcaneus: precision and variations during a 120-Day bed rest

This study reports on the precision and variation of quantitative ultrasound (US) parameters [broadband ultrasonic attenuation (BUA) or slope of the frequency-dependent attenuation in dB/MHz and speed of sound (SOS m/second)] after 120 days of continuous bed rest in six normal male volunteers. Quantitative US was measured at the calcaneus using a new US bone imaging scanner. The measurements were carried out on both heels at approximately 2-week intervals. The short-term precision was 0.31% for SOS and 2.8% for BUA. The long-term precision was 0.58% for SOS, 4.7% for BUA. A significant decrease of SOS values of −26 m/second (P < 0.0001) for the right heel and −17 m/second (P < 0.05) for the left heel was found at the group level. In terms of percentage change this represents −1.7% for the right heel and −1.1% for the left heel. These percentage decrements were 3.5–5.5 times that of the short-term precision and 2–3 times that of the long-term precision of the technique. At the individual level, the decrease of SOS was statistically significant (P < 0.05) or marginally significant (P < 0.1) for four out of 6 subjects. For 2 other subjects, similar trends were observed, but without reaching statistical significance. BUA did not change significantly during follow-up. These results are consistent with previous findings on changes of ultrasonic properties from the calcaneus during aging, pregnancy, or therapy, showing that calcaneus SOS is a valuable index of bone loss. These preliminary data suggest that prolonged exposure to simulated weightlessness may lead to a lower SOS, which then could be used for the follow-up of bone demineralization occurring during long-term space flights. Received: 5 January 1999 / Accepted: 1 July 1999     

Clinical Observations with a New Specific Assay for Bone Alkaline Phosphatase: A Cross-Sectional Study in Osteoporotic and Pagetic Subjects and a Longitudinal Evaluation of the Response to Ovariectomy,Estrogens, and Bisphosphonates

The purpose of this study was to examine the serum levels of bone alkaline phosphatase (BALP) measured with a new assay in normal and in osteoporotic women, and to evaluate prospectively its responsiveness to changes of bone metabolism. The following groups of subjects were studied: (1) 95 healthy women (44–75 years) (22 pre- and 73 postmenopausal) and 35 osteoporotic women [vertebral bone mineral density (BMD) more than 2.5 SD below the normal adult mean]; (2) 10 women (44–50 years) ovariectomized (OVX) for benign uterine diseases, examined before and 12 months after surgery; (3) 16 OVX women (36–54 years), examined before and after 12 months of transdermal estrogen replacement therapy (50 μg/day); (4) 12 previously untreated pagetic patients (4 women and 8 men, 50–80 years), examined before and 3 months after the I.V. administration of clodronate (600 mg) or alendronate (5 mg) for 2 consecutive days. The median BALP value was 11.6 U/liter (25–75th percentiles: 10.5–12.7; range 7.7–19.3) in healthy premenopausal (PreMP) women and significantly higher (median: 16.8 U/liter; 25–75th percentile: 13.8–21.8; P < 0.01) in postmenopausal (PostMP) women. There was a clear age-related increase in normal subjects (r = 0.43; P < 0.001). In the osteoporotic group, BALP levels, as well as other biochemical parameters of bone turnover, were not significantly different from those of normal women when adjusted for age. In OVX women, BALP levels showed a marked increase 12 months after surgery (median: 113%; 25–75th percentile: 87–139%), significantly higher than the increase of total ALP (median: 43%; 25–75th percentile: 25–66%; P < 0.001), and similar to the increases of serum osteocalcin and urinary hydroxyproline. Transdermal estrogen treatment prevented the BALP increase, even if no reduction was observed; total ALP showed a similar behavior. The basal levels of BALP were significantly elevated in pagetic patients (median: 91 U/liter; range 18–610 U/liter) and correlated to the scintigraphic extent of the disease (r = 0.76; P < 0.01). Three months after the I.V. administration of bisphosphonates, the decrease of BALP was more marked than that of total ALP (median: −54% versus −41%; P < 0.05). In conclusion, these results suggest that BALP measurement with this immunoassay may be clinically useful, and more sensitive than total ALP, in the assessment of bone turnover during changes of the estrogen status as well as in monitoring the effects of treatments that modify the metabolic activity of the skeleton. Received: 25 January 1996 / Accepted: 3 May 1996     

Linkage and Association for Bone Mineral Density and Heel Ultrasound Measurements with a Simple Tandem Repeat Polymorphism near the Osteocalcin Gene in Female Dizygotic Twins

In this confirmatory candidate gene study, we investigated possible linkage and association for bone density, heel ultrasound and bone turnover with the osteocalcin gene using the nearby (50–180kb) microsatellite marker D1S3737. Non-identical twin sisters aged 18–75 years at first interview were recruited for the study from the St Thomas’ UK Adult Twin Registry with 1366 women being genotyped for marker D1S3737. Linkage, allelic association and joint linkage and association tests were carried out using quantitative transmission disequilibrium tests (QTDT), along with post-hoc multivariate tests of linkage and association. Phenotypes tested were bone mineral density (BMD) at the spine, left forearm and left total hip; quantitative ultrasound measurements of the heel including velocity of ultrasound (VOS) and broadband ultrasound attenuation (BUA); and bone turnover markers, urine deoxypyridinoline (DPD), serum osteocalcin, bone specific and total alkaline phosphatase (ALP). BMD and ultrasound variables showed evidence of pleiotropic linkage (p= 0.05) and association (p= 0.02) with the marker in postmenopausal women. Bone markers showed little or no evidence of linkage and association for any age group. Evidence for pleiotropic linkage appeared to be strongest for BUA and spine BMD in postmenopausal women. The univariate test statistic for BUA was χ² ₁=12.8 (p= 0.0003), equivalent to a LOD score of 2.8. DPD showed borderline evidence of linkage to the marker for women of all ages. Multivariate model-fitting showed allele 10 to be negatively associated with BMD, VOS and BUA via a common pathway, suggesting the putative functional polymorphism affects both bone content and structure through shared underlying metabolic pathways. It is likely that the alleles are in linkage disequilibrium with functional polymorphism(s) in or nearby the osteocalcin gene, which may contribute to the onset of osteoporosis. Received: 24 January 2002 / Accepted: 25 April 2002     

Influence of Bone Quality on Precision of Calcaneal Ultrasonometry

This study was designed to determine the changes in precision of the ultrasound parameters speed of sound (SOS), broadband ultrasound attenuation (BUA), and stiffness index (SI) as a function of bone quality. The instrument used in this investigation was the LUNAR Achilles. Of the 608 female patients who had paired measurements with repositioning, 200 had t scores ≥−1 and 408 had t scores ≤−2.5, thus rendering a normal and a grossly abnormal group for comparison of precision results. It was found that the median precision error (CV%) for BUA was 1.99% for normal bone and 1.44% for abnormal bone (P= 0.02). No significant difference was obtained between median precision errors in normal and abnormal bone for the parameters SOS and SI, which were 0.23% and 0.19%, and 2.15% and 2.02%, respectively. In the interquartile range, the mean precision errors for SOS and BUA were significantly different in normal and abnormal bone: SOS was 0.25% and 0.21%, respectively, and BUA was 2.31% and 1.85%, respectively. No significant change was registered for SI. Precision error appears to decrease slightly at lower values for calcaneal variables. Received: 21 August 1996 / Accepted: 5 March 1997     

Comparison of Quantitative Calcaneal Ultrasound and Dual Energy X-ray Absorptiometry in the Evaluation of Osteoporotic Risk in Children with Chronic Rheumatic Diseases

Osteoporosis is a common complication in children with chronic rheumatic diseases (CRD). Although dual energy X-ray absorptiometry (DXA) is increasingly being used to determine bone mineral density (BMD) in children, it exposes the subject to ionizing radiation and does not provide a measure of true bone density; in fact, in growing bones the increase in BMD is mainly caused by the increase in bone size. In recent years, quantitative ultrasound techniques (QUS) have been used in radiation-free assessment of bone density and ``bone quality' by measurement of the ultrasound waves attenuation by bone (BUA). In the present study we made a direct comparison of BUA in the calcaneum, determined by the pediatric contact ultrasound bone analyzer (CUBA) with lumbar BMD measured by DXA, in a group of 6–18-year-old patients with CRD. The study group consisted of 53 patients affected with juvenile rheumatoid arthritis (n = 29), systemic lupus erythematosus (n = 13), and juvenile dermatomyositis (n = 11). Mean age was 13.02 ± 2.69 years. In 22 patients (19 girls, 3 boys) both DXA and CUBA were repeated after 1 year in order to assess the mean percentage rate of BMD and BUA change over this time. Both lumbar spine BMD and calcaneal BUA measurements were lower in the CRD patients compared with a control group (P < 0.001). Calcaneal BUA was significantly correlated (r = 0.83, P < 0.001) with lumbar spine BMD. Age and sex correction (Z-score) did not change the relationship between BUA and BMD (r = 0.80, P < 0.001). A significant correlation between the mean percentage of variation (Δ%) of BMD and BUA (r = 0.76, P < 0.001) was also demonstrated in the 22 patients who were evaluated prospectively. Portability, ease of use, lower cost, and absence of radiation make CUBA a promising means of evaluating BMD in children. Received: 12 December 1998 / Accepted: 13 January 2000     

Ultrasound Bone Densitometry of the Os Calcis in Children and Adolescents

The aim of the present investigation was to evaluate reference data and to examine whether there were weight-, height-, age-, and sex-related differences of the quantitative ultrasound bone parameters for healthy children and adolescents. A total of 3299 healthy Caucasian children and teenagers (1623 girls and 1676 boys), age range from 6–18 years (mean age 11.4 ± 3.4 years for boys and mean age 11.5 ± 3.3 years for girls) were examined by quantitative ultrasound densitometry (QUS) using the bone sonometer SAHARA (Hologic Inc., Waltham, MA, USA), a waterless, dry system. The parameters broadband ultrasound attenuation (BUA) [dB/MHz] and speed of sound (SOS) [m/second] were evaluated on the right heel in relation to age, sex, weight, and height. There is no correlation between the ultrasound bone parameter SOS and age, height, and weight. BUA increases with age, height, and weight. Significant differences in SOS and BUA between girls and boys were found to probably be caused by the different onset of growth phases and the onset of puberty. SOS and BUA are influenced by changes of bone mineral density. But BUA is dependent on bone size, too. In conclusion, ultrasound bone densitometry is a useful measuring method showing the physiological bone development in childhood and adolescence. The presented results can be used as reference data. Further studies in children with disorders influencing bone metabolism will show in what way various patterns of osteopenia in childhood can be detected. Received: 20 August 1999 / Accepted: 20 April 2000 / Online publication: 22 September 2000     

Quantitative Ultrasound of the Calcaneus and Falls Risk in the Institutionalized Elderly: Sex Differences and Relationship to Vitamin D Status

Very frail older people constitute an increasing proportion of aging populations and are likely to contribute substantially to costs due to osteoporosis. Quantitative ultrasound (QUS) of the calcaneus is potentially a simple method for assessing fracture risk in frail elderly, but there have been few studies of male/female differences in QUS or its relationship to falls risk or vitamin D status, which is often subnormal in this population. We studied QUS, falls risk and serum 25(OH)-vitamin D in subjects living in institutional aged care facilities (hostels or nursing homes). The study sample comprised 294 men (mean age 81.2 years, range 65–102 years) and 899 women (mean age 86.7 years, range 65–104 years). Broadband ultrasound attenuation (BUA) and velocity of sound (VOS) were higher in men than women by approximately 30% and 2% respectively (p<0.0001) and this difference was maintained at all ages. Serum 25(OH)D levels were higher in men than women (p<0.001) but vitamin D deficiency was very common in both sexes and serum 25(OH)D was not associated with QUS in either sex. There was no significant decline in BUA or VOS with age in men; however, for women BUA declined by 2.8–4.7% per decade and VOS by 1% per decade (both p<0.001). Mean BUA T-scores were −1.55 and −2.48 at age 90 years in men and women. Quadriceps strength and weight but not serum 25(OH)D were significantly associated with BUA. These data suggest only minor loss occurs at the calcaneal site in BUA and VOS with very old age in either sex. Received: 7 March 2002 / Accepted: 5 June 2002 Correspondence and offprint requests to: Professor Philip Sambrook, Royal North Shore Hospital, St Leonards, NSW 2065, Australia. Tel: +61 2 9926 7281. Fax: +61 2 9906 1859. e-mail: sambrook@med.usyd.edu.au     

Influence of body composition on quantitative ultrasound parameters of the os calcis in a population-based sample of pre- and postmenopausal women

Body mass is known to be related to measures of bone mineral density (BMD) as well as to parameters of quantitative ultrasound (US). To examine the effect of the body compartment's fat mass and lean body mass on quantitative ultrasonic bone parameters, data from a sample of 3241 German women were analyzed. Anthropometric measures, including skinfold thickness, were obtained from standardized measurements, and fat and lean body mass were derived from classical regression formulas based on skinfold measurements. Ultrasonic bone measurements were performed on the right os calcis, and speed of sound (SOS) and broadband ultrasound attenuation (BUA) were determined. Women were grouped into pre- and postmenopausal status; postmenopausal women were further stratified into ever and never hormone-replacement user. Correlation analysis indicated lean body mass to be stronger correlated with BUA than fat mass in both pre- (r = 0.23; P= 0.0001) and postmenopausal women with (r = 0.19; P= 0.0001) and without hormone replacement therapy (HRT) (r = 0.26; p = 0.0001). SOS demonstrated very small or no associations with body mass or its components. Multiple linear regression models were used to describe the relationship among body weight, fat mass, and lean body mass on BUA after adjustment for confounding variables. Both in pre- and postmenopausal women lean body mass was more strongly related to BUA than fat mass. However, body mass measures explained only small amounts of the overall variance in BUA (R²= 1–3% in premenopausal women; R²= 1% postmenopausal with HRT; R²= 4–5% in postmenopausal women without HRT). In conclusion, the strong influence of body mass and its components previously reported for BMD was not observed for quantitative ultrasonic bone parameters. Received: 5 January 1999 / Accepted: 1 July 1999     

Genetic Variation in α2HS-Glycoprotein Is Related to Calcaneal Broadband Ultrasound Attenuation in Older Women

Calcaneal broadband ultrasound attenuation (BUA) is an independent predictor of hip and vertebral fractures. BUA is under genetic control, but the specific genes contributing to BUA are not well defined. We examined the relationship between genetic variation in α₂HS-glycoprotein (AHSG), an abundant noncollagenous protein of bone matrix, and calcaneal BUA. Genetic polymorphism in AHSG was determined in 222 Caucasian women (age 66–92) enrolled in the Pittsburgh Study of Osteoporotic Fractures clinical center by isoelectric focusing of serum samples. Calcaneal BUA and bone mineral density (BMD) were measured on the same foot with a Walker Sonix UBA 575⁺ and single X-ray absorptiometry. Hip and spine BMD were determined with a Hologic QDR-1000 densitometer using dual-energy X-ray absorptiometry. AHSG polymorphism was not significantly related to hip, lumbar spine, or calcaneal BMD. Compared with the homozygous AHSG*2 women, calcaneal BUA was 13% lower in heterozygous (P < 0.05) and 16% lower in homozygous AHSG*1 women (P < 0.05). This relationship persisted after controlling for age, weight, height, walks for exercise, and calcaneal BMD. Current and self-reported height were also lowest in homozygous AHSG*1 women, intermediate in heterozygous women, and highest among homozygous AHSG*2 subjects. These results suggest that the AHSG polymorphism may contribute to the genetic influence on calcaneal BUA and stature. Received: 28 August 1997 / Accepted: 8 January 1998     

Influence of Physical Activity on Ultrasound and Dual-Energy X-ray Absorptiometry Bone Measurements in Peripubertal Girls: A Cross-Sectional Study

The aim of this cross-sectional study was to investigate whether two types of physical exercise affect the growing skeleton differently. We used calcaneal quantitative ultrasound measurements (QUS) and dual-energy X-ray absorptiometry (DXA) for measurement of bone mineral density (BMD), and to test how QUS values reflect the axial DXA values in these various study groups. A total of 184 peripubertal Caucasian girls aged 11–17 years (65 gymnasts, 63 runners, and 56 nonathletic controls) were studied. Weight, height, stage of puberty, years of training, and the amount of leisure-time physical activity were recorded. Broadband ultrasound attenuation (BUA) and sound of speed (SOS) through the calcaneus were measured. The BMD of the femoral neck and the lumbar spine were measured by DXA. The differences in mean values of bone measurements among each exercise group were more evident in pubertal than prepubertal girls. The mean BUA and SOS values of the pubertal gymnasts were 13.7% (77.8 dB/MHz versus 68.4 dB/MHz, P < 0.05) and 2.2% (1607.7 m/s versus 1572.4 m/s, P < 0.001) higher than of the controls, respectively. The mean BMD of the femoral neck in the pubertal gymnasts and runners was 20% (0.989 g/cm² versus 0.824 g/cm², P < 0.001) and 9.0% (0.901 g/cm² versus 0.824 g/cm², P < 0.05) higher than in the controls, respectively. The amount of physical activity correlated weakly but statistically significantly with all measured BMD and ultrasonographic values in the pubertal group (r = 0.19–0.35). The correlation between ultrasonographic parameters and BMD were weak, but significant among pubertal runners (r = 0.47–0.55) and controls (r = 0.39–0.42), whereas the DXA values of the femoral neck and the ultrasonographic parameters of the calcaneus did not correlate among highly physically active gymnasts. By stepwise regression analysis, physical activity accounted for much more of the variation in the DXA values than the ultrasonographic values. We conclude that the beneficial influence of exercise on bone status as measured by ultrasound and DXA was evident in these peripubertal girls. In highly active gymnasts the increase of the calcaneal ultrasonographic values did not reflect statistically significantly the BMD values of the femoral neck. Received: 28 June 1999 / Accepted: 2 November 1999     

Changes in Bone Mass and Bone Turnover Following Ankle Fracture

Bone loss and increased bone turnover are recognized local changes after a fracture, but the exact patterns of these changes after different fractures are unclear. We aimed to investigate the changes in bone density and biochemical markers following ankle fracture. Fourteen subjects (7 postmenopausal women and 7 men, mean age 63 years) were recruited following fracture of the distal tibia and fibula. Bone mineral density (BMD) of the ankle and proximal femur were measured by dual-energy X-ray absorptiometry (DXA) and quantitative ultrasound (QUS) of the calcaneus at 0, 6, 12, 26 and 52 weeks after fracture. Serum and urine samples were collected at 0, 3 and 7 days and at 2, 4, 6, 12, 26 and 52 weeks after fracture to measure markers of bone turnover. For bone formation we measured: bone alkaline phosphatase (iBAP), osteocalcin (Oc), procollagen type I N-terminal propeptide (PINP); and for bone resorption: tartrate-resistant acid phosphatase (TRAcP), deoxypyridinoline (iFDpd), N-telopeptides of type I collagen (NTx). We used the nonfractured limb to calculate values for baseline BMD and QUS. There was a significant decrease in BMD at the ultradistal ankle (p<0.001), the trochanteric region of the hip (p<0.01) and QUS of the heel after ankle fracture. This bone loss was maximal for ultradistal ankle BMD by 6 weeks at 13% (p<0.001) and for the trochanter by 26 weeks at 3% (p<0.01). The ankle BMD returned to baseline at 52 weeks but the trochanter BMD did not. Velocity of sound (VOS) decreased at 6 weeks by 2% (p<0.01) and broadband ultrasound attenuation (BUA) by 15% (p<0.01). VOS recovered completely by 52 weeks, but BUA did not return to baseline. Bone formation markers increased significantly between 1 and 4 weeks by 11–78% (p<0.01), and iBAP returned to baseline at 52 weeks but PINP and Oc remained elevated. Bone resorption markers did not increase and NTx was decreased at 52 weeks. We conclude that BMD decreased distal and immediately proximal to the fracture line when measured with DXA and QUS. Ankle BMD and heel VOS recovered at 52 weeks (trochanteric BMD and heel BUA did not) and the bone turnover markers returned toward baseline. Received: 27 January 1999 / Accepted: 19 April 1999     

Radial and Metacarpal Bone Mineral Density and Calcaneal Quantitative Ultrasound Bone Mass in Normal Japanese Women

The purpose of this study was to examine the effect of lifetime physical activity of farmers on skeletal status. Seventy-one healthy, postmenopausal women (mean age 52.3 ± 5.9 years, range 42–61 years) who worked professionally on farms were compared with 78 matched controls (mean age 51.8 ± 5.5 years, range 42–61 years). Broadband ultrasound attenuation (BUA) and speed of sound (SOS) at the os calcis were measured using an ultrasound transmission imaging system. Bone mineral density (BMD) of the lumbar spine and femoral neck were measured by dual-energy X-ray absorptiometry (DXA). Differences in BUA, SOS, and BMD between farmers and controls were expressed relative to standard deviation (SD) of the farmers. Farmers had significantly higher density values than controls (difference = 1.3 SD in the spine and 1.5 SD in the femoral neck, P < 0.0001 for both comparisons). Ultrasound values were significantly higher in the farmers compared with the controls in calcaneus (difference = 1.1 SD for BUA and 0.7 SD for SOS, P < 0.0001 for both comparisons). The difference of spine BMD, femoral neck BMD, BUA, and SOS between farmers and controls, as judged by comparison of the slopes of the regression lines, was unchanged with age and years since menopause. These results suggest that lifetime physical activity has a positive effect on bone status of postmenopausal farmers. Received: 19 March 1998 / Accepted: 7 August 1998     

Imaging Ultrasonometry of the Calcaneus: Dependence on Calcaneal Area

The purpose of this study was (1) to investigate the dependence of broadband ultrasound attenuation (BUA) and speed of sound (SOS) measured in a circular region of interest (ROI) having a fixed size on calcaneal area and (2) to examine whether the normalization of ultrasonic variables for the area of the calcaneus provides better differentiation of diseased subjects from healthy individuals. Ultrasound variables were estimated in 169 healthy postmenopausal women (mean age 66.5 years, range 42–87 years) and 39 women with vertebral fractures (mean age 72.9 years, range 51–86 years). A minimum attenuation ROI, 15 mm in diameter, with a commercial imaging ultrasonometer was used. Significant relationships were found between both ultrasonic variables and calcaneal area (r²= 0.06, P < 0.001 for BUA, r²= 0.12, P < 0.0001 for SOS). Normalization of ultrasound variables (BUAn and SOSn) was based on the regression equations of the relationships among BUA, SOS, and calcaneal area. In a precision study, nine women were examined five times each to determine the errors arising from both the repositioning of the foot and selection of the calcaneal area. The reproducibility errors of BUA, SOS, BUAn, SOSn, and area were 0.87%, 0.20%, 1.07%, 0.27%, and 3.72%, respectively. Significant differences were found between the areas under the ROC curve for BUAn and BUA (area under the curve = 0.93 for BUAn versus 0.90 for BUA, P= 0.003) as well as for SOSn and SOS (area under the curve = 0.85 for SOSn versus 0.79 for SOS, P= 0.003). Normalization of ultrasound variables for calcaneal area improves the discrimination of clinical studies. Received: 7 June 1999 / Accepted: 18 January 2000     

Correlations Among Bone Mineral Density,Broadband Ultrasound Attenuation,Mechanical Indentation Testing,and Bone Orientation in Bovine Femoral Neck Samples

Broadband ultrasound attenuation (BUA) of the calcaneus has been found to correlate with bone mineral density (BMD) of the femoral neck. The purpose of this study was to determine if a correlation exists among femoral neck BUA, femoral neck BMD, and incremental indent depth, a qualitative indicator of local mechanical bone strength, in bovine samples, and if this correlation is dependent upon orientation. For 12 of the bovine samples obtained, BUA was measured at the femoral neck and was followed by a BMD determination of the same area. A 19 mm diameter bicortical core containing the center of the area of interest was removed, transversely cut into 7 mm, thick disks, and tested for hardness by indent depth. For these tests, BMD was well correlated with BUA (R²= 0.85, P < 0.001). An inversely proportional relationship with a modest correlation was found between indent depth and BMD (R²= 0.59, P= 0.026), and indent depth and BUA (R²= 0.57, P= 0.031). In a second set of tests involving 15 different bovine samples, a bicortical core was removed from the femoral neck. A trabecular bone cube measuring 1.5 cm on a side was removed from the center of the core. BUA and BMD measurements were made along the anterior–posterior (AP), medial–lateral (ML), and cephalic–caudal (CC) aspects of the cube. The cubes were randomly separated into three groups, cut in half perpendicular to the axis of interest, and tested for hardness by indent depth. In these tests, no significant difference was found in BMD among the three orientations of the cubes scanned (P= 0.77). In contrast, the BUA along the ML orientation of the cube was significantly greater than that along the AP orientation (P < 0.05). No significant difference was found in the incremental indent depth measurements among cube orientations (P= 0.41). In the test involving only trabecular bone, a much higher correlation between BMD and incremental indent depth was found regardless of cube orientation (R²= 0.64, P < 0.001). The data indicate that BUA, but not BMD, is affected by trabecular orientation, and that BMD is negatively correlated with incremental indent depth. Received: 18 July 1995 / Accepted: 19 July 1996     

Associations of Early Premenopausal Fractures with Subsequent Fractures Vary by Sites and Mechanisms of Fractures

In a retrospective population-based study we assessed whether and how self-reported former fractures sustained at the ages of 20–34 are associated with subsequent fractures sustained at the ages of 35–57. The 12,162 women who responded to fracture questions of the baseline postal enquiry (in 1989) of the Kuopio Osteoporosis Study, Finland formed the study population. They reported 589 former and 2092 subsequent fractures. The hazard ratio (HR), with 95% confidence interval (CI), of a subsequent fracture was 1.9 (1.6–2.3) in women with the history of a former fracture compared with women without such a history. A former low-energy wrist fracture was related to subsequent low-energy wrist [HR = 3.7 (2.0–6.8)] and high-energy nonwrist [HR = 2.4 (1.3–4.4)] fractures, whereas former high-energy nonwrist fractures were related only to subsequent high-energy nonwrist [HR = 2.8 (1.9–4.1)] but not to low-energy wrist [HR = 0.7 (0.3–1.8)] fractures. The analysis of bone mineral density (BMD) data of a subsample of premenopausal women who underwent dual x-ray absorptiometry (DXA) during 1989–91 revealed that those with a wrist fracture due to a fall on the same level at the age of 20–34 recorded 6.5% lower spinal (P= 0.140) and 10.5% lower femoral (P= 0.026) BMD than nonfractured women, whereas the corresponding differences for women with a former nonwrist fracture due to high-energy trauma were −1.8% (P= 0.721) and −2.4% (P= 0.616), respectively. Our results suggest that an early premenopausal, low-energy wrist fracture is an indicator of low peak BMD which predisposes to subsequent fractures in general, whereas early high-energy fractures are mainly indicators of other and more specific extraskeletal factors which mainly predispose to same types of subsequent fractures only. Received: 21 February 1996 / Accepted: 24 September 1996     

Determination of Calcaneal Ultrasound Properties Ex Situ: Reproducibility, Effects of Storage, Formalin Fixation, Maceration, and Changes in Anatomic Measurement Site

The objective of this study was to determine the reproducibility of ultrasonic bone properties with a system for measuring calcanei ex situ; the influence of changes of the measurement site; and the effects of fixation, storage, and maceration. We examined 14 fixed calcanei and 12 fresh bones. Ultrasonic measurements were performed ex situ after degassing, using an Achilles+ system and a special positioning device. The instrument precision was 0.16% for speed of sound (SOS), 1.4% for broadband ultrasonic attenuation (BUA), and 1.8% for the stiffness index (SI). The short-term precision was 0.54%, 1.9%, and 2.8%, respectively. A defined shift of the measurement site (5 mm distal of the middle) led to unpredictable changes in ultrasound (US) properties (r = 0.65 for SOS, 0.82 for BUA, and 0.75 for SI). Embalment with 4% formalin/96% alcohol caused a systematic decrease in SOS, an increase in BUA, and a decrease in SI (mean =−12.7 units; P < 0.001), the effect increasing with time. However, values at 6 months of fixation and later were highly correlated with those in fresh specimens (r = 0.95 for the SI). Two weeks storage in degassed and normal solution had only modest effects on ultrasound properties. Maceration did not lead to a systematic increase or decrease of ultrasound variables, but introduced unpredictable changes (r = 0.64–0.94). We conclude that in comparative biomechanical studies it is feasible to measure calcaneal specimens embalmed in formalin/alcohol ex situ, if the primary interest is not in the absolute values but in the correlation with mechanical failure loads at other skeletal sites. Received: 27 August 1998 / Accepted: 12 March 1999     

Usefulness of Ultrasound in Sudeck's Atrophy of the Foot

Quantitative ultrasound (QUS) of bone has been proposed as an inexpensive and radiation-free device method of assessing skeletal status. QUS has been widely used in the assessment of osteoporosis. Until now only few data are available on the usefulness of QUS in different disorders, such as Sudeck's atrophy. To evaluate the ability of QUS in the diagnosis and monitoring of regional osteoporosis, we investigated 19 patients (12 women and 7 men, age range 30–65 years) with osteoporosis of the foot (Sudeck's atrophy), as evidenced by X-ray study and Technetium-99 bone scan. In all patients we measured speed of sound (SOS), broadband ultrasound attenuation (BUA), and stiffness of the calcaneus using Lunar Achilles Ultrasound, both in the affected and unaffected foot. Bone mineral density at the lumbar spine, by DXA (Hologic QDR 1000), was also performed. QUS was repeated after 3 and 6 months of treatment with salmon calcitonin (100 IU I.M. every second day). At baseline, SOS, BUA, and stiffness, expressed as T-score, were −1.9, −2.4, and −2.4 in unaffected feet and −2.9, −5.1, and −4.3, respectively, in affected feet. The difference between the unaffected and affected foot was significant for SOS, BUA, and stiffness (P < 0.001). No significant difference was found in QUS parameters in the unaffected foot during the study period. After 3 and 6 months of treatment, SOS increased in the affected foot by 0.2% and 0.3%, BUA increased by 6.2% and 8.2%, and stiffness by 7.5% and 11.1%, respectively. In conclusion, BUA and stiffness seem to be influenced more than SOS by Sudeck's atrophy; QUS, namely, BUA and stiffness, significantly increase with calcitonin treatment. In conclusion, QUS is a sensitive tool in the diagnosis of Sudeck's atrophy of the foot and is adequate for measuring improvement in bone status following treatment. Received: 7 June 1997 / Accepted: 15 October 1997     

Relationships Between Static Histomorphometry and Ultrasound in the Human Calcaneus

The aim of this study was to explore the relationship(s) between histomorphometric measurements of cancellous bone structure and ultrasound. Ultrasonic measurements were made using a CUBA research system consisting of a pair of 1 Mhz unfocused transducers. Speed of sound (SOS) and broadband ultrasonic attenuation (BUA) were determined in 15 human cadaveric heels, with mean precision for all measurements coefficients of variation (CV) = 0.6% and 12%, respectively. The calcaneus was dissected and a 7.5 mm transcortical cylinder was removed from the path of ultrasound (US) transmission. The cortices were removed and the remaining cancellous core was sectioned into approximately 5 mm blocks, numbered from 1 to 6 (medial-lateral). Histomorphometric measurements were performed on decalcified, 5 μm-thick sections from blocks 1–6 using an automatic color image analysis system. There were significant differences between blocks 1 and 3–6 for BS/TV, BV/TV, Tb.N, and Tb.Sp (all P < 0.001), all decreasing in a medial-lateral direction (except Tb.Sp), implying that the medial portion of the calcaneus had more trabeculae with less spacing between them than the lateral portion. Furthermore, Tb.Th and BS/BV variables were uniform across the calcaneus, suggesting that individual trabeculae were of similar dimension. We found no significant correlations between US and histomorphometric parameters either averaged over all blocks or by using each block region separately. In conclusion, this study does not support the notion that US measurements of SOS and BUA through the heel reflect calcaneal cancellous bone structure, however, further studies using larger sample sizes may be warranted. Received: 20 August 1998 / Accepted: 1 November 1998     

The Role of Collagen Abnormalities in Ultrasound and Densitometry Assessment: In Vivo Evidence

There is little information concerning how the mutation of collagen affects bone mineralization and the assessment of bone properties. To estimate these influences, we performed ultrasonic assessments of the calcaneus and bone mineral density (BMD) measurements of the hip and lumbar spine. Females with diseases related to the mutation of collagen [Ehlers-Danlos syndrome (EDS) type III and systemic sclerosis (SSc)] participated in this study. We compared the broadband ultrasound attenuation (BUA and UBI-4), the average transit time through the heel (TTH), and a multiple factor index (UBI-4T) with control subjects matched on age, race, and menstrual status. Both groups of patients had BMD of the spine (L2–L4) within the normal range for their age and sex (for EDS: n = 23, 1.14 ± 0.14 g/cm² and z-score = 0.37; for SSc: n = 15, 0.98 ± 0.15 g/cm² and z-score = 0.20). EDS and SSc subjects had lower BMD of the femoral neck (FN) compared with controls (for EDS: 0.91 ± 0.13 g/cm², z-score =−0.41, P= 0.025; for SSc 0.67 ± 0.13 g/cm², z-score =−0.92, P= 0.006). Subjects with EDS and SSc also had lower BUA values (P= 0.051–0.001) compared with controls. After adjusting for body weight, height, and the level of physical activity, the difference in FN BMD between EDS or SSc and controls became marginal (EDS: P= 0.072; SSc: P= 0.086). However, the significant difference for BUA between subjects and controls remained for EDS (P= 0.008), and disappeared for SSc (0.70) after adjusting for weight, height, level of physical activity, and BMD. These results suggest that the abnormalities of collagen may impact on bone mass measurements differently depending on skeletal site, modality of the assessment, and the source and nature of collagen defects. To determine whether collagen properties influence QUS, proper models in vivo and in vitro should be used. Received: 1 June 1998 / Accepted: 1 November 1998