Osteoporosis: Shepherd JA

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 The initial use of radio-isotopes as the photon source has been replaced by the use of X-ray technology.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.

Lewiecki EM, Watts NB, McClung MR, Petak SM, Bachrach LK, Shepherd JA, Downs RW, Anonymous00133. · New Mexico Clinical Research and Osteoporosis Center, Albuquerque, New Mexico 87106, USA. · J Clin Endocrinol Metab. · Pubmed #15292281 links to  free full text

Abstract: The International Society for Clinical Densitometry (ISCD) periodically holds Position Development Conferences for the purpose of establishing standards and guidelines for indications, acquisition, and interpretation of bone density tests. Topics are selected for consideration by the ISCD Scientific Advisory Committee, reviewed by scientific working groups, and presented to an international panel of experts. Topic categories addressed to date include indications for bone density testing, selection of reference databases for T-scores and Z-scores, clinical applications for central and peripheral bone densitometry, serial bone density testing, instrument precision assessment, phantom scanning and calibration testing, requirements for a bone density report, nomenclature, and diagnosis of osteoporosis in postmenopausal women, premenopausal women, men, and children. After an open session for public comment and discussion, the panel convenes for consideration of each topic and makes recommendations for positions to the ISCD Board of Directors. Recommendations that are accepted become the Official Positions of the ISCD. This Special Report summarizes the methodology of the ISCD Position Development Conferences and presents selected Official Positions of general interest.

Genant HK, Li J, Wu CY, Shepherd JA. · Osteoporosis and Arthritis Research Group, Department of Radiology, University of California, San Francisco, CA 94143-0628, USA. · J Clin Densitom. · Pubmed #11090235 No free full text.

Abstract: Vertebral fractures are the most common consequence of osteoporosis, and are an important risk factor for subsequent fractures. Patients with reduced bone mineral density (BMD) and vertebral fractures have significantly increased risk for future fractures, indicating great potential for the combined use of fracture assessment and BMD in risk evaluation. Despite the established importance of fractures, however, vertebral assessment is not typically performed in the clinical evaluation of patients at risk for osteoporosis. Radiographs are the accepted standard for assessment of fractures, but are rarely obtained in osteoporosis assessment for a variety of practical reasons, including cost, radiation dose, and the lack of office-based radiological facilities. Clinical assessment of fractures is difficult because most are asymptomatic. Consequently, this strong risk factor for osteoporotic fractures is often overlooked. High-resolution lateral spine images, obtained on advanced fan-beam dual X-ray absorptiometry (DXA) systems, provide a practical, low-radiation dose, point-of-care methodology for assessment of vertebral fractures, and have the potential to address this important clinical need. In this article, we review the importance of vertebral fractures and the methods of assessing them. We also review clinical data supporting the feasibility of visual evaluation of lateral spine images obtained using a fan-beam DXA system, and discuss the potential positive impact of this new methodology on clinical patient evaluation.

Shepherd JA, Morgan SL, Lu Y. · Department of Radiology, University of California at San Francisco, San Francisco, CA 94143-0946, USA. · J Clin Densitom. · Pubmed #18455677 No free full text.

Abstract: One of the long-standing frustrations of clinical densitometry practice is not being able to compare bone mineral density (BMD) measures taken on different densitometers and know if the difference represents a true change. Recently, a method for comparing measures on different systems was published. This method, called the generalized least significant change (GLSC) requires after a procedure to quantify the precision of both systems as well as the in vivo cross-calibration relationship when there is a difference in the technology of the systems. We followed this procedure when a Hologic QDR-4500A was replaced with a Hologic Discovery/W even though these systems would be similar if not identical for hip and spine measures. Thirty participants were scanned twice on each system at the hip and spine. We found that the precisions of each system were similar and the differences in the average BMD values from the spine phantom and in vivo measures for the total spine, total hip, and neck regions were less than 1%. However, the correlation coefficients ranged from 0.96 to 0.98. The magnitude of change needed for significance was typically twice as large for intersystem scan (6-10%) comparisons than intrasystem (3-6%). In summary, we have presented an example of how the GLSC is calculated and used in a clinical practice. The results show that there is a substantial loss in sensitivity to change when comparing scans taken on different systems even in this case of similar technology. A revision of the International Society for Clinical Densitometry's policies for comparing scans from systems of the same technology may be appropriate.

Fan B, Lewiecki EM, Sherman M, Lu Y, Miller PD, Genant HK, Shepherd JA. · Department of Radiology, University of California, 185 Berry Street, Suite 350, San Francisco, CA 94107, USA. · Osteoporos Int. · Pubmed #18373054 No free full text.

Abstract: SUMMARY: The precision of Hologic Apex v2.0 analysis software is significantly improved from Hologic Delphi v11.2 software and is comparable to GE Lunar Prodigy v7.5 software. Apex and Delphi precisions were, respectively, 1.0% vs. 1.2% (L1-L4 spine), 1.l % vs. 1.3% (total femur), 1.6% vs. 1.9% (femoral neck), and 0.7% vs. 0.9% (dual total femur). INTRODUCTION: Precision of bone mineral density (BMD) measurements by dual-energy X-ray absorptiometry (DXA) is known to vary by manufacturer, model, and technologist. This study evaluated the precision of three analysis versions: Apex v2.0 and Delphi v11.2 (Hologic, Inc.), and Prodigy v7.5 (GE Healthcare, Inc.) independent of technologist skill. METHODS: Duplicate spine and dual hip scans on 90 women were acquired on both Delphi and Prodigy DXA systems at three clinics. BMD measures were converted to standardized BMD (sBMD) units. Precision errors were described as a root-mean-square (RMS) standard deviations and RMS percent coefficients of variation across the population. RESULTS: Apex and Delphi values were highly correlated (r ranged from 0.90 to 0.99). Excluding the right neck, the Apex precision error was found to be 20% to 25% lower than the Delphi (spine: 1.0% versus 1.2% (p < 0.05), total hip: 1.1% versus 1.3% (p < 0.05), right neck: 2.3% versus 2.6% (p > 0.1)). No statistically significant differences were found in the precision error of the Apex and Prodigy (p > 0.05) except for the right neck (2.3% versus 1.8% respectively, p = 0.03). CONCLUSION: The Apex software has significantly lower precision error compared to Delphi software with similar mean values, and similar precision to that of the Prodigy.

Prevrhal S, Shepherd JA, Faulkner KG, Gaither KW, Black DM, Lang TF. · Department of Radiology, UCSF, San Francisco, CA 94107, USA. · J Clin Densitom. · Pubmed #18280192 No free full text.

Abstract: Hip structural analysis (HSA) estimates geometrical and mechanical properties from hip dual-energy X-ray absorptiometry (DXA) images and is widely used in osteoporosis trials. This study compares HSA to volumetric quantitative computed tomography (QCT) measurements in the same population. A total of 121 women (mean age 58 yr, mean body mass index 27 kg/m2) participated. Each woman received a volumetric QCT scan and DXA scan of the left hip. QCT scans were analyzed with in-house software that directly computed geometric and mechanical parameters at the neck and trochanteric regions. DXA HSA was performed with an implementation by GE/Lunar. Pair-wise linear regression of HSA variables was conducted by method to site matched QCT variables for bone density, cross-sectional area, and cross-sectional moment of inertia (CSMI) of the femur neck. HSA correlated well with QCT (r2=0.67 for neck bone mineral density [BMD] and 0.5 for CSMI) and standard DXA at the neck (r2=0.82 for BMD). HSA and volumetric QCT compared favorably, which supports the validity of a projective technique such as DXA to derive geometrical properties of the proximal hip.

Shepherd JA, Blake GM. · Department of Radiology, University of California, San Francisco, CA, USA. · J Clin Densitom. · Pubmed #17993399 No free full text.

This publication has no abstract.

Shepherd JA, Lu Y. · Department of Radiology, University of California, San Francisco, CA 94143-0946, USA. · J Clin Densitom. · Pubmed #17616413 No free full text.

Abstract: In this article, we derive a generalized expression for the least significant change (LSC), which we call the generalized LSC (GLSC), to be used when an individual is measured on 2 different systems. The commonly used LSC is defined as the least amount of change between 2 measurements over time that must be exceeded before a change can be considered true (with 95% confidence). The LSC has clinical applications in monitoring disease progression or treatment effects in bone mineral density (BMD) and bone mineral content. Mathematically, the "ideal" LSC (ILSC) is 2.77 times the precision errors for measures on a single system. When BMD values of an individual are measured by 2 different systems, the LSC will depend not only on the precision errors of both systems but also on the calibration relationship between the systems. Like the ILSC, the GLSC is a simple equation applicable for inter machine comparisons. The GLSC can be defined for any 2 systems with measures obtained from cross-calibration and precision studies using the protocols recommended by the International Society for Clinical Densitometry. We validated the GLSC using 10,000 simulated measurements taken between 2 systems and offer several common uses of the GLSC such as system upgrades within a single manufacturer and replacement of 1 manufacturer by another. We found that when upgrading a Hologic QDR-2000 to a QDR-4500, GLSC was twice as large as the QDR-2000 LSC (0.0432 and 0.0215 g/cm2, respectively). The GLSC was 2.6 (spine) to 3.6 (total hip) times larger than the LSC when comparing scans between the Hologic Delphi and the GE Lunar Prodigy. We also explore how the magnitude of the correlation coefficient and sample size change the GLSC and show that a correlation coefficient less than 0.95 increases the %GLSC to above 10%, and that increasing study sample sizes beyond 30 in the cross-calibration studies can only decrease the magnitude of the GLSC accuracy by 4%. We conclude that the GLSC, defined using commonly used clinical cross-calibration and precision assessments, is the most accurate method to compare scans between dual-energy X-ray absorptiometry systems.

Shepherd JA, Fan B, Lu Y, Lewiecki EM, Miller P, Genant HK. · Department of Radiology, University of California, 185 Berry Street, Ste. 350, San Francisco, CA 94143-0946, USA. · Osteoporos Int. · Pubmed #16823544 No free full text.

Abstract: INTRODUCTION: Precision error in bone mineral density (BMD) measurement can be affected by patient positioning, variations in scan analysis, automation of software, and both short- and long-term fluctuations of the densitometry equipment. Minimization and characterization of these errors is essential for reliable assessment of BMD change over time. METHODS: We compared the short-term precision error of two dual-energy X-ray absorptiometry (DXA) devices: the Lunar Prodigy (GE Healthcare) and the Delphi (Hologic). Both are fan-beam DXA devices predominantly used to measure BMD of the spine and proximal femur. In this study, 87 women (mean age 61.6+/-8.9 years) were measured in duplicate, with repositioning, on both systems, at one of three clinical centers. The technologists were International Society for Clinical Densitometry (ISCD) certified and followed manufacturer-recommended procedures. All scans were acquired using 30-s scan modes. Precision error was calculated as the root-mean-square standard deviation (RMS-SD) and coefficient of variation (RMS-%CV) for the repeated measurements. Right and left femora were evaluated individually and as a combined dual femur precision. Precision error of Prodigy and Delphi measurements at each measurement region was compared using an F test to determine significance of any observed differences. RESULTS: While precision errors for both systems were low, Prodigy precision errors were significantly lower than Delphi at L1-L4 spine (1.0% vs 1.2%), total femur (0.9% vs 1.3%), femoral neck (1.5% vs 1.9%), and dual total femur (0.6% vs 0.9%). Dual femur modes decreased precision errors by approximately 25% compared with single femur results. CONCLUSIONS: This study suggests that short-term BMD precision errors are skeletal-site and manufacturer specific. In clinical practice, precision should be considered when determining: (a) the minimum time interval between baseline and follow-up scans and (b) whether a statistically significant change in the patient's BMD has occurred.

Melton LJ, Looker AC, Shepherd JA, O'Connor MK, Achenbach SJ, Riggs BL, Khosla S. · Division of Epidemiology, Department of Health Sciences Research, Mayo Clinic College of Medicine, 200 First Street S.W., Rochester, MN 55905, USA. · Osteoporos Int. · Pubmed #15812599 No free full text.

Abstract: The ability of regional data from whole body scans to provide an accurate assessment of site-specific BMD, osteoporosis prevalence and fracture risk has not been fully explored. To address these issues, we measured total body (TBBD) and site-specific BMD in an age-stratified population sample of 351 women (21-93 years) and 348 men (22-90 years). We found an excellent correlation between AP lumbar spine and total body lumbar spine subregion BMD (r2=0.92), but weaker ones for total hip compared to pelvis region (r2=0.72) or between total wrist and left arm subregion from the whole body scan (r2=0.83). The error in estimating site-specific BMD from total body regions ranged from 4.3% (lumbar spine) to 11.2% (femoral neck) in women and from 4.9 to 11.1%, respectively, in men. Site-specific versus regional measurements at the lumbar spine and total hip/pelvis provided comparable overall estimates of osteoporosis prevalence, but disagreed on the status of individuals; measurements at whole body regions underestimated osteoporosis as assessed at the femoral neck or total wrist. All measurements were associated with a history of various fractures [age adjusted odds ratios (OR), 1.3 to 2.1 in women and 1.2 to 1.5 in men] and were generally interchangeable, but femoral neck BMD provided the best estimate of osteoporotic fracture risk in women (OR, 2.9; 95% CI, 1.7-5.0). Although there are strong correlations between BMD from dedicated scans of the hip, spine and distal forearm and corresponding regions on the whole body scan, the measurements provide somewhat different estimates of osteoporosis prevalence and fracture risk.

Binkley N, Kiebzak GM, Lewiecki EM, Krueger D, Gangnon RE, Miller PD, Shepherd JA, Drezner MK. · University of Wisconsin Osteoporosis Clinical Center and Research Program, Madison, Wisconsin, USA. · J Bone Miner Res. · Pubmed #15647812 No free full text.

Abstract: In attempt to improve diagnostic agreement between manufacturers, a recent software update incorporated NHANES III data in GE Lunar densitometers. As a result, the femur neck and trochanter T-scores were lowered, and osteoporosis prevalence was increased. Use of a recalculated young-normal SD for the GE Lunar-adjusted NHANES III database improved diagnostic agreement and is recommended. INTRODUCTION: Use of manufacturer-specific normative databases for T-score derivation leads to discordance in T-score values and differences in diagnostic classification. To address this issue, the International Committee for Standards in Bone Measurement (ICSBM) recommended the NHANES III database for femur T-score derivation. Acquired on Hologic (Hol) instruments, this database requires conversion equations for application to other DXA systems. NHANES III total femur (TF) conversions for GE Lunar (GE) have previously been available, and femoral neck (FN) and trochanter (TR) equations were reported recently. Per the ICSBM recommendation, GE Lunar incorporated these values into their female database. This should produce T-score and diagnostic agreement between Hol and GE instruments; however, this has not been evaluated. MATERIALS AND METHODS: We compared GE femur scans in 115 postmenopausal women using software before and after the NHANES III software update. Subsequently, T-scores derived from femur scans obtained on GE and Hol densitometers were compared in a different group of 89 postmenopausal women. RESULTS: The NHANES III software update had no effect on measured BMD (g/cm2) at any femur region. However, because of changes in values used for T-score calculation (increase in the mean young-normal BMD at the FN and TR and a reduction in SD at the TR), the T-scores were lower (mean, 0.48 and 0.68, respectively) at the FN and TR using post-NHANES III software. Consequently, this update increased femur osteoporosis prevalence in these 115 women from 7.8% to 18.3%. Comparison of GE with Hol total proximal femur T-scores revealed a minimal difference (<0.1) and equal diagnoses of osteoporosis. FN and TR differences were larger, with mean GE T-scores lower than Hol (p < 0.001) by 0.17 and 0.50, respectively, thereby introducing osteoporosis diagnostic disagreement (13 [GE] versus 9 [Hol]). Our evaluation suggested that this disparity resulted from direct application of published NHANES III SDs at the FN and TR. As such, we applied the conversion formulae to the NHANES III published Hologic data and found the FN and TR SDs were greater than assumed by GE. Using our recalculated SD to derive T-scores reduced the mean GE/Hol T-score difference to 0.03 at the FN and 0.32 at the TR and resolved osteoporosis diagnostic disagreement. CONCLUSION: The GE NHANES III software update leads to lower FN and TR T-scores than obtained with Hol or prior GE software. Recalculation of the young-normal SD reduces this difference and is recommended. Clinicians are advised to avoid using the TR for diagnosis or, at a minimum, use caution when making treatment decisions based solely on T-score at this site.

Prevrhal S, Fox JC, Shepherd JA, Genant HK. · Osteoporosis and Arthritis Research Group, Department of Radiology, University of California-San Francisco, San Francisco, California 94117, USA. · Med Phys. · Pubmed #12557971 No free full text.

Abstract: Measurement of the width of thin structures such as the cortical shell of the vertebral body or femoral neck with computed tomography (CT) is limited by the spatial resolution of the CT system. Limited spatial resolution exists both within the CT image plane and perpendicular to it and can be described by the in-plane point spread function (PSF) and the across-plane slice sensitivity profile (SSP), respectively. The goal of this study was to confirm that errors of thickness measurement of thin structures critically depend on the spatial positioning of the object and the spatial resolution limitations of CT in all three dimensions, and to assess the size of the errors themselves. We compared computer models that incorporated both effects to experimentally assessed cortical thicknesses of the European Spine Phantom. Analysis included varying CT slice width, the orientation of measurement and angle beta of misalignment of longitudinal scanner and phantom axes. Agreement of models with measurements was good in all configurations with an overall error of 0.17 mm. This showed that PSF and SSP are adequate system characteristics to predict deviation of measured values from true widths. Errors between measurements and true cortical thickness values delta(true) averaged to 1.5 mm were strongly positively correlated with slice width d and beta. When the across-plane partial volume effect was eliminated, limited in-plane resolution still accounted for overestimation of delta(true) by 0.68 (137%), 0.27 (27%), and 0.06 mm (4%) for delta(true)=0.5, 1.0, and 1.5 mm, respectively. For delta(true) of 1.0 mm and above, it was shown that although the absolute cortical thickness values might not be accurately measurable, relative differences between two values are reflected in measurement. Implications for cortical thickness measurement are that the spinal cortical shell is too thin, whereas accurate assessment at locations of the femoral neck exhibiting a thicker cortical shell of both difference and absolute values should be possible with CT even for larger misalignment angles, especially when a smaller CT slice width is chosen.

Grigorian M, Shepherd JA, Cheng XG, Njeh CF, Toschke JO, Genant HK. · Osteoporosis and Arthritis Research Group, Department of Radiology, University of California at San Francisco, San Francisco, CA, USA. · Osteoporos Int. · Pubmed #12181618 No free full text.

Abstract: The lack of standardization in bone mineral density (BMD) measurements is known. Several studies have been carried out to cross-calibrate the axial dual X-ray absorptiometry (DXA) devices. Recently, a number of peripheral DXA (pDXA) densitometers have been introduced. In this study we evaluated the agreement between two heel DXA devices on BMD and T-scores. A total of 99 females aged 21-78 years (ca. 16 per decade) had their non-dominant heel BMD measured using the PIXI (Lunar Inc.) and the Apollo (Norland Medical) pDXA scanners. The mean BMD values were 0.492 and 0.607 g/cm(2) and the mean T-scores using manufacturers' specified reference data were -0.07 and -0.25 for the PIXI and Apollo, respectively. Both the BMD and T-score intermachine relationships were highly correlated but showed significant nonidentity slopes and non-zero offsets. The diagnostic comparison on T-scores resulted in 86% agreement between the instruments (weighted kappa score of 0.550). Normalizing the reference peaks and SDs using this study's young adult population BMD results removed the systematic T-score disagreement. We found that PIXI and Apollo are highly correlated. Differences in BMD values are mainly due to different region of interest (ROI) definitions and additional T-score disagreement reflects the difference in normative databases.

Shepherd JA, Kerlikowske KM, Smith-Bindman R, Genant HK, Cummings SR. · Department of Radiology, Osteoporosis and Arthritis Research Group, University of California at San Francisco, 94143, USA. · Radiology. · Pubmed #11997567 links to  free full text

Abstract: Dual x-ray absorptiometry (DXA) was used to quantify breast density with a phantom and with cadaveric breasts. With DXA, percentage of fat correlated with percentage of glandular density of the phantom (r > 0.998) and with density at mammography (r(adjusted) = 0.83). DXA precision (SD) was 0.5% without and 1.1% with breast repositioning. DXA devices can be used to accurately and precisely estimate breast tissue density.

Njeh CF, Chen MB, Fan B, Grigorian M, Shepherd JA, Saeed I, Genant HK. · Osteoporosis and Arthritis Research Group, Department of Radiology, University of California San Francisco, 94143-1349, USA. · J Ultrasound Med. · Pubmed #11758027 No free full text.

Abstract: OBJECTIVE: To evaluate a new gel-coupled calcaneal quantitative ultrasound system, Osteospace (Medilink, Montpellier, France), which was designed to assess the status of bone in the calcaneus. METHODS: The study group consisted of 215 healthy white women aged 20 to 85 years and 51 white women aged 60 to 86 years with osteoporotic fractures. Fifty-two healthy women aged 50 to 85 years were randomly selected from the healthy cohort as the control group. All the women had calcaneal quantitative ultrasonic measurements. The women with osteoporotic fractures and the control group also had proximal femur and lumbar anteroposterior spine bone mineral density measurements using dual X-ray absorptiometry. Bone mineral density was also measured in a subgroup of 54 women at the calcaneus. RESULTS: There was a significant inverse correlation of broadband ultrasound attenuation and speed of sound with age (P < .001). Short-term measurement precision values expressed as coefficients of variation were 1.72% for broadband ultrasound attenuation and 0.64% for speed of sound, and standardized short-term precision values were 6.09% for broadband ultrasound attenuation and 3.87% for speed of sound. The correlations between the quantitative ultrasonic parameters and calcaneal bone mineral density were 0.69 (P = .0001) for broadband ultrasound attenuation and 0.45 (P = .0008) for speed of sound. Both quantitative ultrasonic parameters and all bone mineral density measurements of the hip and spine differed significantly between the control and osteoporotic fracture groups (P < .01). Age-, weight-, and height-adjusted odds ratios per SD decrease were as follows: broadband ultrasound attenuation, 1.79; speed of sound, 1.83; spine bone mineral density, 2.34; femoral neck bone mineral density, 1.69; and total hip bone mineral density, 1.85. The areas under the receiver operating characteristic curve for quantitative ultrasound parameters and bone mineral density measurements were close, ranging from 0.75 to 0.80. CONCLUSIONS: This new quantitative ultrasound system can detect age- and menopause-related influences on skeletal status and can discriminate healthy women from those with osteoporotic fractures in a manner comparable with that of bone mineral density measurement by dual X-ray absorptiometry.

Blake GM, Shepherd JA. · No affiliation provided · J Clin Densitom. · Pubmed #17993402 No free full text.

This publication has no abstract.