Osteoporosis: Fuerst T

Hans DB, Shepherd JA, Schwartz EN, Reid DM, Blake GM, Fordham JN, Fuerst T, Hadji P, Itabashi A, Krieg MA, Lewiecki EM. · Geneva University Hospital, Geneva, Switzerland. <> · J Clin Densitom. · Pubmed #18442759 No free full text.

Abstract: Peripheral assessment of bone density using photon absorptiometry techniques has been available for over 40 yr. The initial use of radio-isotopes as the photon source has been replaced by the use of X-ray technology. A wide variety of models of single- or dual-energy X-ray measurement tools have been made available for purchase, although not all are still commercially available. The Official Positions of the International Society for Clinical Densitometry (ISCD) have been developed following a systematic review of the literature by an ISCD task force and a subsequent Position Development Conference. These cover the technological diversity among peripheral dual-energy X-ray absorptiometry (pDXA) devices; define whether pDXA can be used for fracture risk assessment and/or to diagnose osteoporosis; examine whether pDXA can be used to initiate treatment and/or monitor treatment; provide recommendations for pDXA reporting; and review quality assurance and quality control necessary for effective use of pDXA.

Njeh CF, Fuerst T, Diessel E, Genant HK. · Osteoporosis and Arthritis Research Group, Department of Radiology, University of California, San Francisco, 350 Parnassus Avenue, Suite 908, San Francisco, CA 94143-1349, USA. · Osteoporos Int. · Pubmed #11305077 No free full text.

Abstract: Trabecular bone plays a significant role in maintaining bone structural integrity. Its density is a significant determinant of bone strength and fracture risk, but there is still unexplained variance. It has been suggested that the ability to measure structural information will improve the estimation of bone strength and fracture risk. Quantitative ultrasound (QUS) is a mechanical wave that can be influenced by bone structure, in addition to bone mineral density (BMD). This article reviews the evidence in the literature supporting or refuting this assumption. Theoretically, the propagation of QUS is influenced by both structure and density of the medium. QUS measurement in vivo shows weak but significant association with axial BMD. However, the association becomes stronger when measured in vitro. Broadband ultrasound attenuation (BUA) exhibits a nonlinear relationship with density over a large density range. When cubes of cancellous bone are measured in the three orthogonal directions, both BUA and speed of sound (SOS) show significant anisotropy which mirrors mechanical anisotropy. QUS has also been shown to correlate significantly with structural parameters measured by histomorphometry. However, structure remains a significant predictor after adjustment for BMD mainly in bovine samples. Other studies using phantoms of bone samples have also demonstrated that QUS is dependent on structure. There is preliminary indication that fractal dimensions are significantly associated with QUS. The ultimate usefulness of structural dependence of QUS will be in its ability to improve bone strength estimation above and beyond density. There is ample evidence documenting the ability of QUS to predict bone strength in vitro. BMD is a significant predictor of bone strength and the additive value of structure in estimating bone strength is variable. Clinically, ultrasound of the calcaneus is measured in one direction (medio-lateral) and the structural variation in this direction may be limited. Nevertheless, QUS can provide useful additional information to that provided by axial BMD due in part to different precision and accuracy errors and to biological discordance. On the whole one could conclude that ultrasound attenuation is due to structural parameters and these variables are also dependent on density.

Njeh CF, Fuerst T, Hans D, Blake GM, Genant HK. · Department of Radiology, University of California, San Francisco, USA. · Appl Radiat Isot. · Pubmed #10028639 No free full text.

Abstract: Osteoporosis is a systematic skeletal disease characterized by low bone mass and microarchitectural deterioration of bone tissue which leads to diminished biomechanical competence of the skeleton and low-trauma or atraumatic fractures. Due to increased awareness of the impact of osteoporosis on the elderly population, the use of bone densitometric techniques is becoming more widespread. Considerable progress has been made in the development of non-invasive methods for the assessment of the skeleton. While DXA and QCT are commonly used techniques, the popularity of other approaches such as RA, SXA and QUS is gaining grounds. QCT has an advantage over the other techniques in its ability to measure the true volumetric density of trabecular or cortical bone. We therefore present an overview of these current techniques for bone mineral density (BMD) measurements. In the second section we discuss the radiation doses incurred in BMD measurements by patients and methods for reducing patient and staff radiation exposure are given. Studies of radiation dose to patient from DXA confirms that patient dose is small (0.08-4.6 muSv) compared to that given by many other investigations involving ionizing radiation. Fan beam technology with increased resolution has resulted in increase patient dose radiation dose (6.7-31 muSv) but this is still relatively small. Carrying vertebral morphometry using DXA also incurs less radiation dose (< 60 muSv) than standard lateral radiographs QCT has radiation dose (25-360 muSv) comparable to simple radiological examination such as chest X-ray but lower than imaging CT. Radiation dose from other techniques such as RA and SXA are in the same order of magnitude as pencil beam DXA. For pencil beam DXA and SXA systems the time average dose to staff from scatter is very low even with the operator sitting as close as 1 m from the patient during measurement. However the scatter dose from fan beam DXA systems is considerable higher and approaches limits set by regulator bodies for occupational exposure.

Genant HK, Lang T, Fuerst T, Pinette KV, Zhou C, Thiebaud D, Diez-Perez A. · Department of Radiology, University of California, San Francisco, CA 94143-0628, USA. · Bone. · Pubmed #15542042 No free full text.

Abstract: Volumetric quantitative computed tomography (vQCT), using multiple thin-slice acquisition, measures three-dimensional volumetric bone mineral density (BMD, mg/cm3). vQCT is often used to measure BMD of lumbar vertebrae and may detect early changes in trabecular, cortical, or integral BMD that extend beyond the technical limits of areal dual X-ray absorptiometry (DXA) BMD measurements. The objective of this study was to determine the effect of 2 years of raloxifene (RLX) treatment on several volumetric BMD measures in a subset of postmenopausal women (n=58) enrolled in the Multiple Outcomes of Raloxifene Evaluation (MORE) trial. Patients in this study were randomized to one of three treatment groups: placebo (n=21), RLX 60 mg/day (n=17), or RLX 120 mg/day (n=20), and all patients received daily calcium (500 mg) and vitamin D (400-600 IU) supplementation. Data from the raloxifene treatment groups were pooled for each analysis. Following 2 years of raloxifene treatment, there was a significant percent change from baseline in the vQCT regions of interest (ROIs) of midintegral BMD, total trabecular BMD, and total integral BMD (P<0.05) compared to placebo, while there was no significant change in the spinal DXA BMD measurement. These data provide the first longitudinal assessment by vQCT of changes in vertebral bone density after 2 years of treatment with raloxifene. vQCT appears to be a valuable technique for measuring the effects of raloxifene treatment in this population of postmenopausal women with osteoporosis.

Kanis JA, Johnell O, Black DM, Downs RW, Sarkar S, Fuerst T, Secrest RJ, Pavo I. · WHO Centre for Metabolic Bone Diseases, University of Sheffield, Sheffield, UK. · Bone. · Pubmed #13678769 No free full text.

Abstract: Raloxifene reduces vertebral fracture risk in postmenopausal women with osteoporosis and established osteoporosis, but its efficacy in women with osteopenia has not been studied. The objective of this study was to evaluate the effect of raloxifene hydrochloride on the risk of vertebral fractures in postmenopausal women with osteopenia and to compare this effect with that in women with osteoporosis as defined by the bone mineral density (BMD) T-score at the hip. We studied the 3204 postmenopausal women with osteopenia or osteoporosis without vertebral fractures at baseline in the Multiple Outcomes of Raloxifene Evaluation trial. Compared with placebo, 60 mg/day raloxifene reduced the risk of new vertebral fractures at 3 years independent of baseline total hip BMD. The relative risk for new vertebral fractures for the raloxifene group compared with placebo was 0.53 (95% CI, 0.32-0.88) for those with osteopenia and 0.31 (0.06-0.71) for those with osteoporosis. In raloxifene-treated women the rate of vertebral fracture was similar in women with osteoporosis (2%) to that in women with osteopenia (1.9%). For clinically apparent vertebral fractures, the relative risk of fracture in the osteopenia group for raloxifene was 0.25 (0.04-0.63) compared with placebo. There were no new clinical vertebral fractures in women with osteoporosis receiving raloxifene, whereas four occurred in the placebo group. We conclude that treatment with 60 mg/day raloxifene significantly decreases the risk of new vertebral fractures and new clinical vertebral fractures in postmenopausal women without baseline vertebral fracture who have osteopenia or osteoporosis.

Siris E, Adachi JD, Lu Y, Fuerst T, Crans GG, Wong M, Harper KD, Genant HK. · Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA. · Osteoporos Int. · Pubmed #12415439 No free full text.

Abstract: Raloxifene reduces the risk of new vertebral fractures, but its effect on the severity of these new fractures has not been determined. The MORE (Multiple Outcomes of Raloxifene Evaluation) trial studied the effects of placebo, raloxifene 60 or 120 mg/day in 7,705 postmenopausal women with osteoporosis. Radiologists assessed new vertebral fractures from radiographs and graded the fracture severity as normal (no fracture) or mild, moderate or severe. New clinical vertebral fractures were defined as new vertebral fractures associated with symptoms, such as back pain, and confirmed in radiographs. In the total study population, the majority (76.4%) of the women who experienced clinical vertebral fractures were diagnosed with new moderate/severe vertebral fractures. In turn, women with moderate/severe vertebral fractures in the overall population were more likely to experience clinical symptoms suggestive of fracture than were women who had new mild-only vertebral fractures. The incidence of new mild-only and moderate/severe fractures was the same in women without prevalent vertebral fractures, but the incidence of new moderate/severe fractures was 2 to 3 times higher than that for new mild-only fractures in women with prevalent vertebral fractures. Raloxifene 60 mg/day decreased the risk of at least 1 new moderate/severe vertebral fracture by 61% in women without prevalent vertebral fractures [RR 0.39 (95% CI 0.17, 0.69)], and by 37% in women with prevalent vertebral fractures [RR 0.63 (95% CI 0.49, 0.83)] at 3 years. The risk reductions for at least 1 new moderate/severe vertebral fracture were not significantly different between the raloxifene doses, in women with and without prevalent vertebral fractures. The effects of raloxifene on significantly decreasing the risk of new moderate/severe vertebral fractures may explain the risk reduction for new painful clinical vertebral fractures observed with raloxifene, and is particularly important in postmenopausal women with severe osteoporosis who are at higher risk for moderate or severe fractures.

Engelke K, Libanati C, Liu Y, Wang H, Austin M, Fuerst T, Stampa B, Timm W, Genant HK. · Synarc Inc, San Francisco, USA. · Bone. · Pubmed #19345291 No free full text.

Abstract: BACKGROUND: Dual-energy X-ray absorptiometry (DXA) allows clinically relevant measurement of bone mineral density (BMD) at central and appendicular skeletal sites, but DXA has a limited ability to assess bone geometry and cannot distinguish between the cortical and trabecular bone compartments. Quantitative computed tomography (QCT) can supplement DXA by enabling geometric and compartmental bone assessments. Whole-body spiral CT scanners are widely available and require only seconds per scan, in contrast to peripheral QCT scanners, which have restricted availability, limited spatial resolution, and require several minutes of scanning time. This study evaluated the accuracy and precision of whole-body spiral CT scanners for quantitatively assessing the distal radius, a common site of non-vertebral osteoporosis-related fractures, and compared the CT-measured densitometric values with those obtained from dual-energy-X-ray absorptiometry. SUBJECTS AND METHODS: A total of 161 postmenopausal women with baseline lumbar spine BMD T-scores between -1.0 and -2.5 underwent left forearm QCT using whole-body spiral CT scanners twice, 1 month apart. QCT volumes of interest were defined and analyzed at 3 specific radial regions: the ultradistal region by using slices at 8, 9, and 10 mm proximal to the ulnar styloid tip; the distal region by a slice 20 mm proximal; and the middle region by a slice 40 mm proximal. BMD, bone mineral content (BMC), volume, and average cortical thickness and circumference were measured. We evaluated QCT accuracy and precision and also report correlations between QCT and DXA for BMD and BMC. RESULTS: Overall accuracy and precision errors for BMD, BMC and volume were consistent with known skeletal QCT technology precision and were generally less than 3%. BMD and BMC assessed by QCT and DXA were correlated (r=0.55 to 0.80). DISCUSSION: Whole-body spiral CT scanners allow densitometric evaluations of the distal radius with good accuracy and very good precision. This original and convenient method provides a tool to further investigate cortical and trabecular bone variables in the peripheral skeleton in osteoporotic patients. These assessments, coupled with evaluation of the effects on cortical and trabecular bone measured in response to therapies for osteoporosis, may advance our understanding of the contributors to non-vertebral fracture occurrence.

Fuerst T, Wu C, Genant HK, von Ingersleben G, Chen Y, Johnston C, Econs MJ, Binkley N, Vokes TJ, Crans G, Mitlak BH. · Synarc, Inc., San Francisco, CA 94105, USA. · Osteoporos Int. · Pubmed #19083074 No free full text.

Abstract: SUMMARY: The utility of vertebral fracture assessment (VFA) by DXA to detect prevalent vertebral fracture in a multicenter setting was investigated by comparison to conventional radiography. While limited by lower image quality, overall performance of VFA was good but had a tendency to miss mild prevalent fractures. INTRODUCTION: In osteoporosis clinical trials standardized spine radiographs are used to detect vertebral fractures as a study endpoint. Lateral spine imaging with dual X-ray absorptiometry (DXA) scanners, known as vertebral fracture assessment (VFA) by DXA, presents a potential alternative to conventional radiography with lower radiation dose and greater patient convenience. METHODS: We investigated in a multicenter setting the ability of VFA to detect fractures in comparison with conventional radiography. The study examined 203 postmenopausal women who had imaging of the spine by DXA and radiography. Three radiologists experienced in vertebral fracture assessment independently read the VFA scans and radiographs using the Genant semiquantitative method on two occasions. CONCLUSIONS: Analyzing the data from all readable vertebrae, the kappa statistic, sensitivity, and specificity ranged from 0.64-0.77, 0.65-0.84, and 0.97-0.98, respectively. Considering only moderate and severe fractures improved the kappa statistic (0.80-0.91) and sensitivity (0.70-0.86). While image quality of VFA is inferior to radiography, the detection of vertebral fractures using visual scoring is feasible. However, VFA underperformed due to unreadable vertebrae and reduced sensitivity for mild fractures. Nevertheless, VFA correctly identified most moderate and severe vertebral fractures. Despite this limitation, VFA by DXA provides an important tool for clinical research.

Lewiecki EM, Keaveny TM, Kopperdahl DL, Genant HK, Engelke K, Fuerst T, Kivitz A, Davies RY, Fitzpatrick LA. · New Mexico Clinical Research & Osteoporosis Center, 300 Oak Street NE, Albuquerque, New Mexico 87106, USA. · J Clin Endocrinol Metab. · Pubmed #18840641 No free full text.

Abstract: CONTEXT: Bone strength and fracture resistance are determined by bone mineral density (BMD) and structural, mechanical, and geometric properties of bone. DESIGN, SETTING, AND OBJECTIVES: This randomized, double-blind, placebo-controlled outpatient study evaluated effects of once-monthly oral ibandronate on hip and lumbar spine BMD and calculated strength using quantitative computed tomography (QCT) with finite element analysis (FEA) and dual-energy x-ray absorptiometry (DXA) with hip structural analysis (HSA). PARTICIPANTS: Participants were women aged 55-80 yr with BMD T-scores -2.0 or less to -5.0 or greater (n = 93). INTERVENTION: Oral ibandronate 150 mg/month (n = 47) or placebo (n = 46) was administered for 12 months. OUTCOME MEASURES: The primary end point was total hip QCT BMD change from baseline; secondary end points included other QCT BMD sites, FEA, DXA, areal BMD, and HSA. All analyses were exploratory, with post hoc P values. Results: Ibandronate increased integral total hip QCT BMD and DXA areal BMD more than placebo at 12 months (treatment differences: 2.2%, P = 0.005; 2.0%, P = 0.003). FEA-derived hip strength to density ratio and femoral, peripheral, and trabecular strength increased with ibandronate vs. placebo (treatment differences: 4.1%, P < 0.001; 5.9%, P < 0.001; 2.5%, P = 0.011; 3.5%, P = 0.003, respectively). Ibandronate improved vertebral, peripheral, and trabecular strength and anteroposterior bending stiffness vs. placebo [7.1% (P < 0.001), 7.8% (P < 0.001), 5.6% (P = 0.023), and 6.3% (P < 0.001), respectively]. HSA-estimated femoral narrow neck cross-sectional area and moment of inertia and outer diameter increased with ibandronate vs. placebo (respectively 3.6%, P = 0.003; 4.0%, P = 0.052; 2.2%, P = 0.049). CONCLUSIONS: Once-monthly oral Ibandronate for 12 months improved hip and spine BMD measured by QCT and DXA and strength estimated by FEA of QCT scans.

Cheng S, Njeh CF, Fan B, Cheng X, Hans D, Wang L, Fuerst T, Genant HK. · Osteoporosis and Arthritis Research Group, Department of Radiology, University of California, San Francisco, 350 Parnassus Avenue, San Francisco, CA 94134-1349, USA. · Br J Radiol. · Pubmed #11806960 links to  free full text

Abstract: There is considerable technological diversity among quantitative ultrasound (QUS) devices used to assess osteoporosis. Because the distance between the transducer and the footplate remains constant, the location of the calcaneus measured will vary with foot size. This study was designed to quantify the variation in bone mineral density (BMD) between a manufacturer's region of interest (ROI_M), which is fixed relative to the footplate, and an anatomical region of interest (ROI_A), which is defined as 20% of calcaneal length. The effect of foot length and width on QUS variables measured using two Food and Drug Administration cleared QUS devices, the Sahara (Hologic) and the Achilles+ (Lunar) was assessed. 26 healthy subjects (12 male and 14 female), aged 22-54 years (35.6+/-10 years) and with foot lengths of 21.5 cm to 29.7 cm (25.1+/-2.3 cm) were recruited. QUS assessments were performed at the right calcaneus. In addition, a Hologic 4500 densitometer was used to measure the BMD of the calcaneus in the ROI_M and ROI_A. The sizes of the ROIs were approximated to the sizes of the transducers of the Sahara and Achilles+ devices. The results showed a significant difference in BMD between the two ROI locations for the Sahara device (BMD 0.642+/-0.135 g cm(-2) vs 0.616+/-0.114 g cm(-2), p=0.014), but no significant difference was found in BMD between the two locations for the Achilles device (BMD 0.661+/-0.120 g cm(-2) vs 0.662+/-0.123 g cm(-2), p=0.818). At the ROI_A, there was a significant difference in BMD between the two QUS devices (p<0.001). The correlation between QUS variables and BMD was slightly higher for the ROI_M (r=0.68-0.79, since this is site-matched) than the ROI_A (r=0.59-0.70) for the Achilles device, while for the Sahara device the correlations were r=0.35-0.40 and r=0.51-0.54, respectively. The smaller ROI of the Sahara device resulted in more than 50% of the subjects having BMD differences of greater than 5% between the ROI_A and the ROI_M, compared with only 20% of the subjects on the Achilles device. ROIs containing cortical bone edge and other soft tissues were found in 58% of cases for the Achilles device and 46% of cases for the Sahara device. The greatest differences occurred in very small and very large feet. Calcaneal length correlated significantly with Sahara speed of sound (SOS), and heel width correlated significantly with Achilles SOS. Heel width also correlated significantly with Sahara broadband ultrasound attenuation (BUA) but not Achilles+ BUA. These results suggest that variation in ROI and bone size might affect the accuracy of QUS measurements, since the calcaneus is heterogeneous both in terms of its external geometry and its internal structure and density.

Prevrhal S, Fuerst T, Fan B, Njeh C, Hans D, Uffmann M, Srivastav S, Genant HK. · Osteoporosis and Arthritis Research Group, Department of Radiology, University of California, San Francisco, 350 Parnassus Avenue, Suite 607, San Francisco, CA 94143-1349, USA. · Osteoporos Int. · Pubmed #11305080 No free full text.

Abstract: This study investigated whether tibial speed of sound (SOS; SoundScan 2000, Myriad Ultrasound Systems, Israel) reflects not only bone mineral density (BMD) but also tibial cortical thickness, as assessed by dual-energy X-ray absorptiometry (DXA) and Quantitative CT (QCT) at a site-matched location. The secondary focus of the study was how tibial SOS compares with BMD at the spine and the hip, the most widely used locations for densitometry. Twenty-two young normal (N) and 23 postmenopausal women with spinal fractures (Fx) (mean (SD) age 35 (8) and 70 (5) years) underwent quantitative ultrasound (QUS) SOS measurement at the left tibial midshaft. From site-matched QCT scans (three 3-mm slices spaced along the QUS measurement region), BMD and cortical thickness were computed (QCT-cBMD, QCT-cTh). The cortex in the CT images was then subdivided into three concentric and equally spaced bands, and QCT-cBMD was computed separately for each band. DXA was performed at the mid-tibia (TIB BMD), at the spine (SPINE BMD) and the hip (total hip, HIP BMD). Correlation coefficients between parameters were determined with least-square linear fits. Intergroup differences were assessed by analysis of covariance, whose r2 value reflects the percentage variation in the data explained by group assignment. SOS correlated significantly with site-matched parameters (QCT-cBMD, OCT-cTh and TIB BMD, all r = 0.6, p < 0.001), SPINE BMD and HIP BMD (both r = 0.5, p < 0.001). Multiple regression with both QCT-cBMD and QCT-cTh against SOS yielded r = 0.7 with both parameters contributing significantly. For the cortex band subdivision, SOS correlated better with QCT-cBMD in the outermost band of the cortex (r = 0.67) than with the more central bands (r = 0.59 and r = 0.53). Group assignment could best explain SPINE BMD (r2 = 0.62) and HIP BMD (r2 = 0.51). SOS was comparable to TIB BMD (r2 = 0.3 vs. r2 = 0.35).: Our findings suggest that the tibial SOS measurement depends on both the thickness and density of the tibia, but is more strongly influenced by the density of the cortex near the surface than by its interior parts. The power of tibial ultrasound to discriminate between normal and fracture patients was less than that of spinal and femoral DXA BMD and comparable to site-matched DXA BMD.

Njeh CF, Hans D, Li J, Fan B, Fuerst T, He YQ, Tsuda-Futami E, Lu Y, Wu CY, Genant HK. · Department of Radiology, University of California, San Francisco 94143, USA. · Osteoporos Int. · Pubmed #11256897 No free full text.

Abstract: Quantitative ultrasound (QUS) is now accepted as a useful tool in the management of osteoporosis. There are a variety of QUS devices clinically available with a number of differences among them, including their coupling methods, parameter calculation algorithms and sites of measurement. This study evaluated the abilities of six calcaneal QUS devices to discriminate between normal and hip-fractured subjects compared with the established method of dual-energy X-ray absorptiometry (DXA). The short-term and mid-term precisions of these devices were also determined. Thirty-five women (mean age 74.5+/-7.9 years) who had sustained a hip fracture within the past 3 years, and 35 age-matched controls (75.8+/-5.6 years) were recruited. Ultrasound measurements were acquired using six ultrasound devices: three gel-coupled and three water-coupled devices. Bone mineral density was measured at the hip using DXA. Discrimination of fracture patients versus controls was assessed using logistic regression analysis (expressed as age- and BMI-adjusted odds ratios per standard deviation decrease with 95% confidence interval) and receiver operating characteristics (ROC) curve analysis. Measurement precision was standardized to the biological range (sCV). The sCV ranged from 3.14% to 5.5% for speed of sound (SOS) and from 2.45% to 6.01% for broadband ultrasound attenuation (BUA). The standardized medium-term precision ranged from 4.33% to 8.43% for SOS and from 2.77% to 6.91% for BUA. The pairwise Pearson correlation coefficients between different devices was highly significant (SOS, r = 0.79-0.93; BUA, r = 0.71-0.92). QUS variables correlated weakly, though significantly, with femoral BMD (SOS, r = 0.30-0.55; BUA, r = 0.35-0.61). The absolute BUA and SOS values varied among devices. The gel-coupled devices generally had a higher SOS than water-coupled devices. Bone mineral density (BMD) and BUA were weakly correlated with weight (r = 0.48-0.57 for BMD and r = 0.18-0.54 for BUA), whereas SOS was independent of weight. All the QUS devices gave similar, statistically significant hip fracture discrimination for both SOS and BUA measures. The odds ratios for SOS (2.1-2.8) and BUA (2.4-3.4) were comparable to those for femoral BMD (2.6-3.5), as were the area under the curve (SOS, 0.65-0.71; BUA, 0.62-0.71; BMD, 0.65-0.74) from ROC analysis. Within the limitation of the sample size all devices show similar diagnostic sensitivity.

Njeh CF, Wu C, Fan B, Hans D, Fuerst T, He Y, Genant HK. · Osteoporosis and Arthritis Research Group, Department of Radiology, University of California, San Francisco, San Francisco, CA 94143-1349, USA. · Ultrasound Med Biol. · Pubmed #11179626 No free full text.

Abstract: This study aimed to evaluate the ability of speed of sound (SOS) measured at the phalanges to estimate simulated wrist fracture load and stress. SOS was measured along the proximal phalanges of the second, third and fourth fingers using an ultrasound (US) system operating in axial transmission mode. The bone mineral density (BMD) of the radius and the phalanges was also measured with quantitative computed tomography (QCT) and dual x-ray absorptiometry (DXA), and the combined cortical thickness (CCT) of the phalanges was measured from hand radiographs. After the measurements were completed, the radius was excised from the cadaver, embedded in polymethylmethacrylate and tested to failure on a servohydraulic testing machine. The configuration of the radius was chosen to simulate a fall onto the hand. Linear regression analysis showed a highly significant correlation between SOS (r = 0.76-0.94, p < 0.001), CCT (r = 0.86-0.90, p < 0.001) and BMD (r = 0.92-0.96, p < 0.0001) in the three proximal phalanges measured. SOS, BMD and CCT were significant predictors of fracture load (r = 0.60-0.69, p < 0.03) and stress (r = 0.65-0.77, p < 0.02). Cortical area and bone mineral content (BMC) of the radius were consistently higher predictors of fracture load (r = 0.76-0.82, p < 0.01 for area and r = 0.78-0.88, p < 0.01 for BMC) than BMD. The correlation of BMC and area was poorer with fracture stress. In a step-wise regression analysis using both phalangeal BMD and SOS, only SOS remained a significant predictor of fracture stress. In forward stepwise regression analysis, both cortical area and SOS were entered into the regression model to estimate fracture load. Only SOS remained significant in the model for estimating fracture stress. Phalangeal BMD was only entered in the combined model with the cortical area at the 4% site (r = 0.84, p = 0.002). Phalangeal SOS is a useful parameter in the assessment of bone status of the radius.

He YQ, Fan B, Hans D, Li J, Wu CY, Njeh CF, Zhao S, Lu Y, Tsuda-Futami E, Fuerst T, Genant HK. · Department of Radiology, University of California, San Francisco 94143-1349, USA. · Osteoporos Int. · Pubmed #10928226 No free full text.

Abstract: The incidence of osteoporotic hip fracture increases in postmenopausal women with low hip bone mineral density (BMD). Dual X-ray absorptiometry (DXA) is the most commonly used technique for the assessment of bone status and provides good measurement precision. However, DXA affords little information about bone architecture. Quantitative ultrasound (QUS) systems have been developed to evaluate bone status for assessment of fracture risk. Our study was designed to assess a new QUS system from Hologic, the Sahara; to compare it with a previous model, the Walker-Sonix UBA 575+; and to investigate whether it is able to discriminate between women with and without fracture. Using both ultrasound devices, the measurements were performed at the heels of 33 postmenopausal women who had recently sustained hip fracture. A control group of 35 age-matched postmenopausal women was recruited for comparison. The total, neck and trochanter femoral BMD values were assessed using DXA for both groups. QUS and DXA measurements were significantly lower in fractured patients (p < 0.005) than in the control group. The short-term, mid-term and standardized short-term precisions were used to evaluate the reproducibility of the two QUS systems. The Sahara showed a better standardized coefficient of variation for broadband ultrasound attenuation (BUA) than did the UBA 575+ (p < 0.001). The correlation of BUA and speed of sound (SOS) between the two QUS devices was highly significant, with an r value of 0.92 for BUA and 0.91 for SOS. However, the correlation between DXA and ultrasound parameters ranged from 0.28 to 0.44. We found that ultrasound measurements at the heel were significant discriminators of hip fractures with odds ratios (OR) ranging from 2.7 to 3.2. Even after adjusting the logistic regressions for total, neck or trochanter femoral BMD, QUS variables were still significant independent discriminators of hip fracture. The areas under the ROC curves of each ultrasound parameter ranged from 0.75 to 0.78, and compared very well with femoral neck BMD (p > 0.05). In conclusion, our study indicated that the calcaneal QUS variables, as measured by the Sahara system can discriminate hip fracture patients equally as well as hip DXA.

Diessel E, Fuerst T, Njeh CF, Hans D, Cheng S, Genant HK. · Osteoporosis and Arthritis Research Group, University of California at San Francisco 94117, USA. · Br J Radiol. · Pubmed #10721316 links to  free full text

Abstract: The purpose of this study was to evaluate a new imaging ultrasound scanner for the heel, the DTU-one (Osteometer MediTech, Denmark), by comparing quantitative ultrasound (QUS) results with bone mineral density (BMD) of the heel and femur from dual X-ray absorptiometry (DXA), and by comparing the DTU-one with another QUS device, the UBA 575+. The regions of interest in the DXA heel scan were matched with the regions evaluated by the two QUS devices. 134 healthy and 16 osteoporotic women aged 30-84 years old were enrolled in the study. In vivo short-term precision of the DTU-one for broadband ultrasound attenuation (BUA) and speed of sound (SOS) was 2.9% and 0.1%, respectively, and long-term precision was 3.8% and 0.2%, respectively. Highest correlations (r) between QUS and BMD measurements were achieved when comparing DTU-one results with BMD in matched regions of the DXA heel scan. Correlation coefficients (r) were 0.81 for BUA and SOS. Highest correlations with the UBA 575+ were 0.68 and 0.72, respectively. The comparison of BMD in different femoral sites with BUA and SOS (DTU-one) varied from 0.62 to 0.69 when including the entire study population. The correlation between BMD values within different sites of the femur tended to be higher (from r = 0.81 to 0.93). When comparing BUA with BUA and SOS with SOS on the two QUS devices, the absolute QUS values differed significantly. However, correlations were relatively high, with 0.76 for BUA and 0.82 for SOS. In conclusion, the results of the new quantitative ultrasound device, the DTU-one, are highly correlated (r = 0.8) with results obtained using the UBA 575+ and with BMD in the heel. The precision of the DTU-one is comparable to other QUS devices for BUA and is high for SOS.

Njeh CF, Hans D, Wu C, Kantorovich E, Sister M, Fuerst T, Genant HK. · Osteoporosis and Arthritis Research Group, Department of Radiology, University of Califormia, 350 Parnassus Avenue, Suite 908, San Francisco, CA 94117-1349, USA. · Med Eng Phys. · Pubmed #10699567 No free full text.

Abstract: To measure the speed of sound (SOS), most quantitative ultrasound (QUS) devices use the transmission mode, whereby two transducers are placed on opposite sides of the sample. This mode is limited to a few specific skeletal sites because of the varying configuration of bone geometry and varying amounts of overlying soft tissue at most other sites. The aim of this study was to address the dependence of SOS measured along the sample on the thickness and composition of the bone sample.Bovine samples from mid-femur and trochanter, and perspex phantoms were used. We prepared the perspex samples in the shapes of blocks and cylinders to investigate the effect of wall thickness on SOS. The thickness of the blocks was decreased in decrements of 1 mm; a 22 mm diameter hole was drilled through the cylindrical samples and the hole size was gradually increased. The second configuration was also used with the bovine samples. For each experimental set-up five SOS measurements were acquired, with the probe aligned along the sample and a mean value computed. All measurements were taken with castor oil as the coupling agent, and in the cylindrical cases, the oil was used to fill the tube.The measurement precision determined as the root mean square coefficient of variation (RMSCV) was determined to be 0.14% and 0.65% for perspex and bovine samples respectively. The measured SOS on the perspex phantom (2760+/-4 m/s) was within the published values for bulk velocity. It was observed that for both perspex and bovine samples the SOS was independent of sample wall thickness greater than the wavelength (2.2 mm, 2.7 mm and 3.5 mm for perspex, trochanter and mid-femur respectively). The SOS decreased with sample wall thickness smaller than the wavelength in concordance with theoretical predictions. The SOS values obtained for bovine samples reflected either totally cortical (mid-femur) or a composite of cortical and cancellous bone (trochanter).

Cheng S, Fan B, Wang L, Fuerst T, Lian M, Njeh C, He Y, Kern M, Lappin M, Tylavsky F, Casal D, Harris S, Genant HK. · Osteoporosis and Arthritis Research Group, University of California, San Francisco, California, USA. · Osteoporos Int. · Pubmed #10663351 No free full text.

Abstract: This study aimed to assess the factors that may influence the distribution and description of broadband ultrasound attenuation (BUA) and to identify specific criteria for diagnostic consideration when collecting BUA reference data. Two hundred Caucasian women (aged 20-79 years) without a history of atraumatic fractures or medicines known to affect bone metabolism were selected for this study. Medical and menstrual history, medication usage, family history of osteoporosis (FHO), physical activity, activities of daily living (ADL), dietary calcium intake, as well as smoking and alcohol consumption were obtained. Broadband ultrasound attenuation (BUA, dB/MHz) was determined in the right foot using a new gel-coupled ultrasound system. BUA was significantly associated with age (p<0.001), body weight (p<0.001), level of physical activity (p = 0.024) and dietary calcium intake (p = 0.023). Smoking, alcohol and coffee consumption and ADL were not associated with BUA (p>0.05). There were no differences in BUA (p>0.05) between those women who reported taking medications or had diseases (known to not affect bone metabolism), were using contraceptives, taking vitamin/mineral supplements and/or had traumatic fractures and their counterparts who did not report these characteristics. Premenopausal women with a FHO had significantly lower BUA values compared with those without a FHO (p = 0.013). When those participants with a FHO were removed from the sample, the peak BUA value was 1.1-4.4% higher and the variability (SD) was reduced by about 3.3-9.3% depending on which age range was used to define the peak BUA value. Consequently, an additional 4.5% of the population were classified as having a T-score <-2. Our results suggest that the impact on BUA of risk factors such as a FHO, body weight, physical activity and dietary calcium intake is similar to that on bone mineral density obtained by dual-energy X-ray absorptiometry (DXA), and thus provides further information on the comparability of quantitative ultrasound and DXA for assessment of risk of fracture. The criteria for calculating the T-score need further study to determine whether young adults with FHO should be included and what cutoff age range should be used in collecting peak values of quantitative ultrasound parameters.

Njeh CF, Richards A, Boivin CM, Hans D, Fuerst T, Genant HV. · Osteoporosis and Arthritis Research Group, UCSF, San Francisco, CA 94117-1349, USA. · J Clin Densitom. · Pubmed #10548820 No free full text.

Abstract: The amplitude-dependent speed of sound (AD-SOS) in the proximal phalanges is reported to be sensitive to osteoporotic changes. We investigated the influence of bone thickness and cortical thickness on AD-SOS. Phantoms made of Perspex were designed to simulate different bone width (11-16 mm) and cortical thickness (3-7.5 mm). The phantoms were designed with two opposing flat and cylindrical surfaces. The effect of cortical thickness was examined by drilling holes (simulating the medullary canal) of different diameters (1-7 mm) in the middle of the Perspex cylinders. The effect of sample thickness was investigated on solid Perspex phantoms of varied lengths. The standardized precision errors of AD-SOS measurement in vivo and in vitro on volunteers and phantoms were 2.8 and 0.9%, respectively. AD-SOS was influenced by the bone width, cortical thickness, and location along the phalanx. A decrease in either cortical width or cortical thickness resulted in a decrease in AD-SOS. The effect is dependent on whether the contact surface is curved or flat. It is possible that a curved surface has a focusing effect on the wave through the porous core, whereas for a flat surface, the path of the waves might not pass through the center. When cortical thickness and bone width were expressed as a ratio, there was a linear relationship between this ratio and AD-SOS through the phantoms. AD-SOS was independent of thickness for samples greater than 11 mm.

Bennett HS, Dienstfrey A, Hudson LT, Oreskovic T, Fuerst T, Shepherd J. · National Institute of Standards and Technology, Gaithersburg, MD 20899, USA. · J Clin Densitom. · Pubmed #17097524 No free full text.

Abstract: This article reports and discusses the results of the recent ISCD-NIST Workshop on Standards and Measurements for Assessing Bone Health. The purpose of the workshop was to assess the status of efforts to standardize and compare results from dual-energy X-ray absorptiometry (DXA) scans, and then to identify and prioritize ongoing measurement and standards needs.