Cross-Calibration and Minimum Precision Standards for Dual-Energy X-ray Absorptiometry: The 2005 ISCD Official Positions
Article Outline
- Abstract
- Introduction
- Methodology
- I. Cross-Calibration Between Similar Makes and Models
- Rationale
- Discussion
- II. Cross-Calibration When Replacing a Whole System for a System With the Same Technology
- Rationale
- Discussion
- III. When No Cross-Calibration Study or BMD Comparison Is Undertaken Between Facilities
- Rationale and Discussion
- IV. Technologist Precision
- Rationale and Discussion
- Summary
- References
- Copyright
Abstract
The International Society for Clinical Densitometry (ISCD) Committee on Standards of Bone Measurement (CSBM) consists of experts in technical aspects of bone densitometry. The CSBM recently reviewed the scientific literature on cross-calibration and precision assessment. A report with recommendations was presented at the 2005 ISCD Position Development Conference (PDC). Based on a thorough review of the data by the ISCD Expert Panel during the conference, the ISCD adopted Official Positions with respect to (1) cross-calibration when changing or replacing hardware; (2) the approach to cross-calibration when an entire system is changed to one made by either the same or a different manufacturer; (3) when no cross-calibration study or bone mineral density (BMD) comparison is done between facilities; and (4) the minimum acceptable precision for an individual technologist. We present here the ISCD Official Positions on these topics that were established as a result of the 2005 PDC, together with the associated rationales and supportive evidence.
Key Words: Standardization, bone densitometry, DXA
Introduction
The International Society for Clinical Densitometry (ISCD) Committee on Standards of Bone Measurement (CSBM) is a committee that was formerly independent and known as the International Committee of Standards in Bone Measurement (ICSBM). The ISCBM was created to address issues of accuracy, standardization, and comparability of densitometers from different manufacturers. Manufacturers of bone densitometry devices were invited to participate in the ICSBM, as were representatives from academic institutions. The ICSBM commissioned studies for the standardization of the posterior/anterior (PA) spinal bone mineral density (BMD) as measured by dual-energy X-ray absorptiometry (DXA) (1), for the standardization of the proximal femur BMD (2), and for the standardization of forearm BMD (3). The results of these studies directly generated approximately 12 publications, and the derived equations are now the standard means of pooling data from different manufacturers. The standardization equations were reported as letters to the editor of selected journals 4, 5, 6, and standardized BMD units are now available on applicable systems. The ICSBM also recommended standardized projectional density units of mg/cm2 (sometimes referred to as areal density) to distinguish it from the manufacturer-specific BMD units typically reported g/cm2.
The ISCD CSBM was recently charged to investigate several topics concerning cross-calibration and technical aspects of bone densitometry. A report with recommendations was presented to the Expert Panel at the ISCD 2005 Position Development Conference. Presented here are the ISCD Official Positions on these topics resulting from that conference, with the supportive evidence and/or justification for these positions.
Methodology
The methods used to develop, and grading system applied to these ISCD Official Positions is presented in the Executive Summary that accompanies this paper. Briefly, all Positions were graded on quality of evidence (good, fair, poor), strength of recommendation and applicability (worldwide or limited).
I. Cross-Calibration Between Similar Makes and Models
ISCD Official Position
Rationale
Historically, the ISCD bone densitometry course has recommended that DXA phantom scans be performed before and after hardware changes, and that if a greater than 1% difference in bone mineral content (BMC), bone area, or BMD was evident, correction factors should be considered (7).
Repositioning the phantom between cross-calibration phantom scans simulates the slight differences seen on daily quality control (QC) charts due to repositioning the phantom. It has not been uniformly recommended by the ISCD before, but is made explicit in this position, to average out the repositioning error in the phantom scans average. Using 10 phantom scans to estimate the system calibration will result in a factor of approximately three improvements in the estimate of the mean measure. For example, taking a single phantom measurement on a system with a phantom precision coefficient of variation (CV)
=
1% means that a single measure has a 67% chance of being within +/− 1% of true measure. If one uses the average value of 10 phantom scans, the uncertainty (standard deviation of the average) would be CV
=
1%/sqrt (10)
=
0.32%. This is a 3.2 times improvement in the certainty for the cross-calibration. The least significant change (LSC) to see a significant change in the system calibration would be 2.77∗0.32
=
0.88%. Thus, if the average of 10 phantom scans is used for cross-calibration, even with a phantom precision of 1%, one could see a significant difference in calibration of less than 1%.
Discussion
DXA systems take measurements on many different regions of interest (ROIs) and the calibration differences before and after system changes can be unique to each ROI. There are several examples in the literature of calibration changes that occurred on ROIs other than the spine, when the spine showed no calibration shift. For example, Blake (8) reported a shift in total hip and neck calibration on a Hologic densitometer without a shift in spine calibration. Blunt et al (9) and Shepherd et al (10) reported shifts in whole body calibration without an associated shift in spine phantom results. Thus, scanning just a spine phantom after hardware changes may not insure that other ROIs, such as the proximal femur or whole body, are still within 1% of the pre-change values. It is not the intention of this Position to suggest that clinical DXA centers buy specialized phantoms for each ROI. Poor calibration agreement of non-spine ROIs is rare: however, without ROI-specific phantom scans, use of the pre-change LSC should be done with this caution. Establishment of a phantom depository available to clinical centers would be a great advantage to the densitometry community, thereby allowing more thorough cross-calibration than can be achieved by a spine phantom alone.
There is no standard method for generating or applying correction factors if they are deemed necessary. A simple tool for making corrections to their data, based on hardware changes such as a very simple MS Excel solution that has: entry of ROI; baseline BMD; follow-up BMD; date of each BMD measure; date of calibration shift; amount of shift; and a simple correction factor report that could be attached to the manufacturer-specific report and filed, would be useful to the densitometry community. System manufacturers are encouraged to implement this type of adjustment in their reporting software. Lastly, for pediatric studies where BMC is used clinically, the average phantom BMC should not shift more than 1%.
II. Cross-Calibration When Replacing a Whole System for a System With the Same Technology
ISCD Official Position
Rationale
It has been the long-standing recommendation of the ISCD that when there are system changes to a new model or make, phantoms alone cannot assure in vivo accuracy. This is supported by many cross-calibration studies that included phantoms and people. An example of different technologies is fan and pencil beam. An example of different makes is Hologic (Hologic, Inc., Bedford, MA) and GE Lunar (GE Healthcare Lunar, Madison, WI). Examples of different models are Lunar DPX-IQ and Lunar Prodigy.
Discussion
This position follows the recommendation originally made by Blake et al. (11) and Blake, Harrison, and Adams (12) for cross-calibrating scanners. It was based on the observation that phantom scans were not sufficient, even for scanners from the same manufacturers (both Hologic and GE Healthcare-Lunar Scanners), to accurately predict in vivo calibration. Blake et al. (11) recommended scanning 20–30 subjects at each skeletal site to achieve an accuracy of 1%. The individual subjects were to be measured on both old and new scanners, preferably on the same day. If in vivo scans were not feasible, then phantoms were suggested but the paper noted that the best phantom for cross-calibration was an area of active research: this is still true (11).
The ISCD position follows this protocol. The standard way to use in vivo data collected for cross-calibration is for the manufacturer to generate a slope and intercept for each ROI, and convert the database of the old system to the new calibration, and upload the old system's database to the new system. There have never been guidelines given on what the LSC should be when comparing the converted old system values to the new system values. In fact, the previous position was to not use the converted system values for quantitative comparison to the new system values. We present a method for doing so. A densitometry center should expect that the inter-system LSC for two densitometers of differing technology would be two to three times higher than the LSC on the same system. However, the inter-system LSC should only be used for the first follow-up measure on the new system. Future scans should be referenced to a reestablished baseline on the new system.
To calculate the inter-system LSC, let X be the BMD measured by the old scanner and Y be the BMD measured on the new scanner. Using linear regression, Y would be related to X by Y
=
a
+
bX. If there were no differences between two scanners, a
=
0 and b
=
1. Otherwise, the old BMD value X will be converted into the corresponding least squares fit of
. What is the appropriate LSC between Y and Ŷ ?
Blake et al (12) suggested using twice the root mean square error (RMSE) for LSC between measures for the measured change to be statistically significant with a P value of 0.05. This, however, assumes an offset fixed to 0 in the linear relationship that may not be justified in all cases. We generalize this simple relationship to include the error of both the old and new scanner in the LSC, and the RMSE is an average error of linear regression. In actuality, the LSC should be increased, depending on the difference between patient's BMD measured by the old scanner (X) relative to the mean BMD of the subjects used in the cross-calibration study. Therefore, the prediction error should not be a constant. Lastly, the regression approach was conditioned on the given X values. For subjects not in the in vivo calibration samples, there is also a precision error of X measurements that needs to be accounted for. In summary, there are three sources of variations that will affect the determination of the inter-system LSC: the precision of the new system; the precision of the old system; and the random variation introduced by in vivo regression prediction.
A general LSC has been proposed by Shepherd and Lu (10) and recommended for use in this Position. This method details how to calculate a LSC between any two DXA systems. A software tool is provided on the ISCD website to calculate the intra- or inter-LSC using this method. The input to this method is the precision of 30 subjects on the old system and the new system, as well as 30 subjects scanned on both systems. It is not necessary to use the same subjects for the precision studies on the old and new systems, nor is it necessary to use the same subjects for the precision studies and the cross-calibration study. The most likely situation though, is that a previous precision study had been done on the old system and that the cross-calibration and precision study on the new system can be performed at the same time. That is, when the old system has existing, established site-specific precision values defined on that system, the cross-calibration study would consist of scanning 30 subjects with one scan per ROI on the old system, and two scans per ROI on the new system. This protocol results in the cross-calibration and precision values for the new system.
III. When No Cross-Calibration Study or BMD Comparison Is Undertaken Between Facilities
ISCD Official Position
Rationale and Discussion
There is no known reasonable way to estimate a LSC without cross-calibration scans. This situation is common, especially when trying to compare results from another clinical center on a report that the patient presents to her physician. This ultimately will be a topic for investigation by a committee of the ISCD.
IV. Technologist Precision
ISCD Official Position
=
5.3%)
=
5%)
=
6.9%)
Rationale and Discussion
It is desirable to have a precision value that represents the minimum acceptable precision that would be acceptable by a technologist. If this minimum standard could not be achieved, then the technologist would need to be retrained.
Fifty-eight recent precision studies 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70 from selected journals were identified and reviewed by the committee. Some of the studies were represented twice, and every effort was made to try to represent a single dataset once in the analysis. Precision is reported in terms of percent coefficient of variation (%CV), since that is what was available from most of the references.
As part of the investigation into these questions, Y. Lu, a committee member and statistician at University of California at San Francisco, performed a meta-analysis on peer-reviewed precision studies. The goal of the analysis was to develop median precision estimates for as many skeletal sites as possible but, principally, the proximal femur and lumbar spine. Study variables that were retrieved for each study were: system make and model; sample size used in the precision estimate; population characteristics, if the precision study was from a peer-reviewed publication; the sponsor of the study; and the precision of the spine, total hip, and femur/neck. There were not enough peer reviewed precision studies found to evaluate bilateral hip precision versus a single hip scan: all hip precision values presented here are from single hip scanning protocols.
We found that virtually all studies listed the precision as %CV instead of a standard deviation. It should be noted that although we are presenting minimum precision standards in terms of %CV, precision expressed as a standard deviation should be used to calculate the LSC, as has been recommended by the ISCD. Multiple precision studies were identified for Hologic, GE Healthcare, and Norland Medical (CooperSurgical) systems. Only one precision study was identified for the DMS Lexxos. Group average precision values were not affected by the inclusion or exclusion of this one DMS Lexxos study. Thus, it was included in the averages. There was not enough power to discern the precision by system generation. The sponsorship of the studies was simplified as government, independent (universities and clinics), manufacturer, or pharmaceutical. There were no significant differences in %CVs among studies of different sponsorships for the spine and neck, but studies sponsored by pharmaceutical trials had a significantly poorer precision at the total hip. This is, however, based on a small number of studies (six or less) in the manufacturer and pharmaceutical sponsored groups. We found no clear trend of precision versus study sample size for the spine, total hip, or neck ROIs.
The meta-analysis precision estimates, and p-values for the co-variants, are shown in Table 1. The precision is presented as a median, an upper 75%tile value, and a 90%tile value. It was thought that clinical sites should be able to achieve the 90%tile precision values or retraining would be necessary.
Table 1. Meta-Precision Study Results
| Percent Coefficient of Variation of | |||
|---|---|---|---|
| Spine | Total Hip | Neck | |
| Median | 1.1% | 1.2% | 1.85% |
| Upper 75 percentile | 1.5% | 1.55% | 2.3% |
| Upper 90 percentile | 1.9% | 1.8% | 2.5% |
| Manufacturer p value | 0.02 | 0.27 | 0.03 |
| Sponsorship p value | 0.78 | 0.16 | 0.60 |
| Sample size p value | 0.64 | 0.93 | 0.85 |
Summary
The ISCD Official Positions contained in this document are based on reasonable standards achievable by most clinics.
References
- Universal standardization for dual x-ray absorptiometry: patient and phantom cross-calibration results. J Bone Miner Res. 1994;9(10):1503–1514
- . Standardization of bone mineral density at femoral neck, trochanter and Ward's triangle. Osteoporos Int. 2001;12(6):438–444
- Universal standardization of forearm bone densitometry. J Bone Miner Res. 2002;17(4):734–745
- . Standardization of measurements for assessing BMD by DXA. [letter] Calcif Tissue Int. 1995;57(6):469
- . Letter to the Editor. Osteoporosis Int. 1997;7:500–501
- . Standardization of proximal femur bone mineral density (BMD) measurements by DXA. [letter] [In Process Citation] Bone. 1997;21(4):369–370
- ISCD Certification Course, Lecture 3 Version 5.3, slide 40.
- . Replacing DXA scanners: cross-calibration with phantoms may be misleading. Calcif Tissue Int. 1996;59(1):1–5
- Hologic whole body phantom: using in vitro data to correct in vivo whole body data. J Bone Miner Res. 2000;15(Supp 1):S398
- Shepherd JA, Lu Y. 2004 Least significant change in bone densitometry for individuals measured on different devices. 16th International Bone Densitometry Workshop, Annecy, France, June 21, 2004.
- . An unexpected change in DXA calibration not detected by routine quality control checks. Osteoporos Int. 1999;9(2):115–120
- . Dual X-ray absorptiometry: cross-calibration of a new fan-beam system. Calcif Tissue Int. 2004;75(1):7–14
- Relationship between lipids and bone mass in 2 cohorts of healthy women and men. Calcif Tissue Int. 2004;74(2):136–142
- . Effects of transdermal estradiol delivered by a matrix patch on bone density in hysterectomized, postmenopausal women: a 2-year placebo-controlled trial. Osteoporos Int. 2002;13(2):176–183
- . Dual X-ray absorptiometry: clinical evaluation of a new cone-beam system. Calcif Tissue Int. 2005;76(2):113–120
- . Household tobacco smoke exposure is negatively associated with premenopausal bone mass. Osteoporos Int. 2002;13(8):663–668
- . Effect of 99mTc-MDP administration on dual-energy X-ray absorptiometry bone mineral density measurements. J Clin Densitom Spring. 2005;8(1):14–17
- . Abnormalities in bone mineral density and bone histology in thalassemia. J Bone Miner Res. 2003;18(9):1682–1688
- . Differential effects of teriparatide on BMD after treatment with raloxifene or alendronate. J Bone Miner Res. 2004;19(5):745–751
- . Improving femoral bone density measurements. J Clin Densitom Winter. 2003;6(4):353–358
- . Identification of men with reduced bone density at the lumbar spine and femoral neck using BMD of the os calcis. J Clin Densitom Summer. 2004;7(2):134–142
- . Effects of cigarette-smoking on bone mass as assessed by dual-energy X-ray absorptiometry and ultrasound. Osteoporos Int. 2002;13(12):932–936
- . Influence of muscle strength, physical activity and weight on bone mass in a population-based sample of 1004 elderly women. Osteoporos Int. 2003;14(9):768–772
- Characterization of common genetic variants in cathepsin K and testing for association with bone mineral density in a large cohort of perimenopausal women from Scotland. J Bone Miner Res. 2004;19(1):31–41
- . Bone mineral density and hip axis length in Singapore's multiracial population. J Clin Densitom. 2004;7(4):406–412
- Effects of exercise on bone mineral density in calcium-replete postmenopausal women with and without hormone replacement therapy. Osteoporos Int. 2003;14(8):637–643
- Alendronate treatment in men with primary osteoporosis: a three-year longitudinal study. Calcif Tissue Int. 2003;73(2):133–139
- . Comparison of ultrasound and X-ray absorptiometry bone measurements in a case control study of female rheumatoid arthritis patients and randomly selected subjects in the population. Osteoporos Int. 2003;14(4):312–319
- . Assessment of fracture risk: value of random population-based samples—the Geelong Osteoporosis Study. J Clin Densitom. 2001;4(4):283–289
- A second-stage genome scan for QTLs influencing BMD variation. Calcif Tissue Int. 2004;75(2):138–143
- . Which bone densitometry and which skeletal site are clinically useful for monitoring bone mass?. Osteoporos Int. 2003;14(12):959–964
- Quantitative trait loci on chromosomes 2p, 4p, and 13q influence bone mineral density of the forearm and hip in Mexican Americans. J Bone Miner Res. 2003;18(12):2245–2252
- . A longitudinal study of the effect of subcutaneous estrogen replacement on bone in young women with Turner's syndrome. J Bone Miner Res. 2003;18(5):925–932
- . Growth hormone increases bone mineral content in postmenopausal osteoporosis: a randomized placebo-controlled trial. J Bone Miner Res. 2003;18(3):393–405
- . The relationship between COLI A1 polymorphisms (Sp 1) and COLI A2 polymorphisms (Eco R1 and Puv II) with bone mineral density in Chinese men and women. Calcif Tissue Int. 2004;75(2):133–137
- . Vitamin D receptor start codon polymorphism (Fok I) and bone mineral density in Chinese men and women. Osteoporos Int. 2002;13(3):218–221
- . Areal and volumetric bone density in Hong Kong Chinese: a comparison with Caucasians living in the United States. Osteoporos Int. 2003;14(7):583–588
- . Reproducibility of volume-adjusted bone mineral density of spine and hip from dual X-ray absorptiometry. J Clin Densitom. 2001;4(4):307–312
- . Bone density monitoring with the total hip site: time for a re-evaluation?. J Clin Densitom. 2004;7(3):269–274
- Age-related bone mineral density, accumulated bone loss rate and prevalence of osteoporosis at multiple skeletal sites in chinese women. Osteoporos Int. 2002;13(8):669–676
- No evidence for linkage and/or association of human alpha2-HS glycoprotein gene with bone mineral density variation in Chinese nuclear families. Calcif Tissue Int. 2003;73(3):244–250
- Bone turnover rate in postmenopausal women: bimodal distribution?. J Clin Densitom. 2001;4(4):343–352
- . Bone resorption and osteoporotic fractures in elderly men: the Dubbo osteoporosis epidemiology study. J Bone Miner Res. 2005;20(4):579–587
- . Supplementation with oral vitamin D3 and calcium during winter prevents seasonal bone loss: a randomized controlled open-label prospective trial. J Bone Miner Res. 2004;19(8):1221–1230
- Uneven deficits in vertebral bone density in postmenopausal patients with primary hyperparathyroidism as evaluated by posterior-anterior and lateral dual-energy absorptiometry. Osteoporos Int. 2002;13(8):618–623
- . Need for precision studies at individual institutions and assessment of size of regions of interest on serial DXA scans. J Clin Densitom. 2003;6(2):97–101
- Effect of CYP1A1 gene polymorphisms on estrogen metabolism and bone density. J Bone Miner Res. 2005;20(2):232–239
- . Pulsed estrogen therapy in prevention of postmenopausal osteoporosis. A 2-year randomized, double blind, placebo-controlled study. Osteoporos Int. 2004;15(2):168–174
- Genetic predisposition for adult lactose intolerance and relation to diet, bone density, and bone fractures. J Bone Miner Res. 2004;19(1):42–47
- Seasonal periodicity of serum vitamin D and parathyroid hormone, bone resorption, and fractures: the Geelong Osteoporosis Study. J Bone Miner Res. 2004;19(5):752–758
- . Hormone therapy and risk of non-vertebral fracture: Geelong osteoporosis study. Osteoporos Int. 2004;15(6):434–438
- . Peak bone mineral density at the hip is linked to chromosomes 14q and 15q. Osteoporos Int. 2004;15(6):489–496
- . Effects of gender and age on the association of apolipoprotein E epsilon4 with bone mineral density, bone turnover and the risk of fractures in older people. Osteoporos Int. 2002;13(9):701–709
- Effects of physical activity and dietary calcium intake on bone mineral density and osteoporosis risk in a rural Thai population. Osteoporos Int. 2004;15(10):807–813
- . Range of change of measured BMD in the femoral neck and total hip with rotation in women. J Bone Miner Metab. 2004;22(5):496–499
- Prevalence and correlates of vertebral fractures in adults with cystic fibrosis. Bone. 2004;35(3):771–776
- Estrogen receptor beta polymorphisms are associated with bone mass in women and men: the Framingham Study. J Bone Miner Res. 2004;19(5):773–781
- Association between a polymorphism affecting an AP1 binding site in the promoter of the TCIRG1 gene and bone mass in women. Calcif Tissue Int. 2004;74(1):35–41
- . Bone mineral density in the proximal femur and contralateral knee after total knee arthroplasty. J Clin Densitom. 2004;7(4):424–431
- BMD at multiple sites and risk of fracture of multiple types: long-term results from the Study of Osteoporotic Fractures. J Bone Miner Res. 2003;18(11):1947–1954
- Relationship between dental panoramic radiographic findings and biochemical markers of bone turnover. J Bone Miner Res. 2003;18(9):1689–1694
- . Dual-energy x-ray absorptiometry measurements of total-body bone mineral during weight change. J Clin Densitom. 2005;8(1):31–38
- Low plasma vitamin B12 is associated with lower BMD: the Framingham Osteoporosis Study. J Bone Miner Res. 2005;20(1):152–158
- . Prevalence of osteoporosis and fractures in a migrant population from southern to northern Italy: a cross-sectional, comparative study. Osteoporos Int. 2003;14(9):734–740
- . Precision of single vs bilateral hip bone mineral density scans. J Clin Densitom. 2003;6(2):159–162
- . Establishment of BMD reference plots and determination of peak BMD at multiple skeletal regions in mainland Chinese women and the diagnosis of osteoporosis. Osteoporos Int. 2004;15(1):71–79
- . Differences in bone density, body composition, physical activity, and diet between child gymnasts and untrained children 7-8 years of age. J Bone Miner Res. 2003;18(6):1043–1050
- Long-term changes in bone metabolism, bone mineral density, quantitative ultrasound parameters, and fracture incidence after spinal cord injury: a cross-sectional observational study in 100 paraplegic men. Osteoporos Int. 2004;15(3):180–189
- Prevention of bone loss in paraplegics over 2 years with alendronate. J Bone Miner Res. 2004;19(7):1067–1074
- . The impact of reproductive and menstrual history on bone mineral density in Chinese women. J Clin Densitom. 2003;6(3):289–296
PII: S1094-6950(06)00187-9
doi:10.1016/j.jocd.2006.05.005
© 2006 The International Society for Clinical Densitometry. Published by Elsevier Inc. All rights reserved.
