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The Effect of 99mTc on Dual-Energy X-Ray Absorptiometry Measurement of Body Composition and Bone Mineral Density
Journal of Clinical Densitometry: Assessment & Management of Musculoskeletal Health, vol. 16, no. 3, 297e301, 2013 Ó Copyright 2013 by The International Society for Clinical Densitometry 1094-6950/16:297e301/$36.00 http://dx.doi.org/10.1016/j.jocd.2012.05.005
Original Article
The Effect of 99mTc on Dual-Energy X-Ray Absorptiometry Measurement of Body Composition and Bone Mineral Density Marie Øbro Fosbøl,* Anders Dupont, Louise Alslev, and Bo Zerahn Department of Clinical Physiology and Nuclear Medicine, Herlev Hospital, Denmark
Abstract Whether the g-emission by radioisotopes influences the outcome of dual-energy X-ray absorptiometry (DXA) measurements is not fully elucidated. The aim of this study was to evaluate the effect of antecedent administration of 99mTc on DXA measurements regarding body composition and bone mineral density (BMD) using a K-edge filter scanner. The phantom measurements were performed by placing a urinary bladder phantom containing 40 mL of radioisotope solution on the pelvic region of a whole-body phantom. Twenty-seven patients attending our department for a routine examination involving the administration of a tracer marked with 99mTc were included. The patients underwent a whole-body DXA scan before and within 2 h after tracer injection using a GE/Lunar Prodigy scanner. Control scans were performed on 40 volunteers, who had not received any radioactive tracer. In both phantom and patient measurements, we found a significant dose-related decrease in fat mass and BMD and a corresponding increase in fat-free mass ( p ! 0.001). Based on the linear regression analysis, we suggest upper dose limits for the measurement of BMD at 0.77 mSv/h and body composition at 0.21 mSv/h (dose rate measured at a distance of 1 m from the patient). Caution should be taken when interpreting the results of DXA scans performed in close temporal proximity to procedures involving the administration of 99mTc. Key Words: Body composition; bone mineral density; dual-energy X-ray absorptiometry; gamma radiation; radiopharmaceuticals.
BMD has been investigated in several studies (3e9). These have shown inconsistent results regarding the confounding effect of tracers marked with 99mTc on DXA measurement of BMD. Evidence suggests that the influence of the radioactive tracer is dependent on the DXA system. No significant effect of 99mTc on BMD has been found in studies using scanners with the pulsed power source (PPS) technology (3,6,8). In contrast, 3 studies using K-edge filter (KEF) scanners have shown a significant decrease in measured BMD following the injection of a 99mTc tracer (5,7,9). The influence of radioactive tracers on DXA measurement of body composition is not fully disclosed. Rosenthall (7) measured fat mass in 15 patients before and after the injection of 99mTc methylene diphosphonate using a KEF DXA scanner and found a significant decrease in fat mass. Sala et al (8) investigated the effect of 99mTc on DXA measurement of body composition in children (aged 3e18 yr). DXA scans were performed using either a PPS or a KEF scanner and no significant change in body composition or BMD was detected.
Introduction Dual-energy X-ray absorptiometry (DXA) is widely used to diagnose osteoporosis and monitor the development of bone mineral density (BMD) during therapy (1). DXA measurement of body composition has numerous clinical applications including the assessment of patients with nutritional disorders or gastrointestinal disease (2). Whenever a DXA scan is requested in close-time proximity to a nuclear medicine procedure, it is important to know whether the g-rays emitted by radiopharmaceuticals interfere with the detection of the X-rays used in the DXA systems. A relation between g-radiation emitted from 99mTc and DXA measurement of
Received 02/17/12; Revised 05/14/12; Accepted 05/17/12. *Address correspondence to: Marie Øbro Fosbøl, MD, Department of Clinical Physiology and Nuclear Medicine, Herlev Hospital, Denmark. E-mail: [email protected]
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The aim of this study was to determine how tracers marked with 99mTc affect BMD and body composition measurements on human beings as well as a whole-body phantom on a KEF system. Our secondary aim was to determine a dose limit of g-radiation from 99mTc below which a DXA scanner will produce reliable results.
Methods and Materials Patient Measurements This is a prospective, longitudinal, single cohort study of 27 patients (12 women and 15 men) undergoing scheduled nuclear medicine procedures (renography [N 5 13], bone scintigraphy [N 5 10], radionuclide ventriculography [N 5 2], lymph drainage scintigraphy [N 5 1], and myocardial perfusion imaging [N 5 1]). All were included after acquiring written informed consent. The exclusion criteria were impaired renal function, impaired cognitive function, pregnancy, body weight more than 135 kg, or metal implants from major orthopedic surgery (hip and knee arthroplasties and femoral or tibial osteosyntheses). The dose of 99mTc ranged from 50 to 800 MBq. Wholebody DXA was performed before and after the administration of 99mTc measuring BMD and body composition using a Lunar Prodigy scanner (GE Lunar, Madison, WI). Radiation dose rate was measured at a distance of 1 m at the level of the urinary bladder before and after each DXA scan using a Rados RDS-200 Universal Survey Meter (Mirion Technologies, San Ramon, CA). The average of the 2 readings was used in the data analysis. The time interval from the injection of the tracer to the second DXA scan varied from 5 min to 2 h depending on the procedure used. Patients were instructed to refrain from food intake, and all fluid input and output were measured between the first and second DXA scan. The effective radiation exposure per whole-body DXA scan was approx 0.37 mSv (2). All patients were supine positioned in exactly the same manner at both DXA scans according to the manufacturers’ manual. Reproducibility of the whole-body DXA scan was
determined on 40 volunteers who were scanned sequentially with full repositioning and no administration of radioactive tracers between measurements. The study was approved by the regional committee on biomedical research ethics (study number H-A-2009-003).
Whole-Body Phantom Measurements As a preliminary study, we conducted measurements on a whole-body phantom. A urinary bladder phantom containing 40 mL of radioisotope solution was placed on the pelvic region of a whole-body phantom (WB Phantom, serial no. WB 1008; Hologic, Inc., Bedford, MA) after which a series of DXA scans were performed and analyzed. The range of 99m Tc activity evaluated in this study was 5e205 MBq (68 sequential measurements). Sixteen control scans were performed on the whole-body phantom on 3 different days without the presence of a radioactive isotope. Mean values are based on the control scans without the presence of a radioactive isotope, whereas slope, intercept, and correlation coefficient are based on the 68 sequential scans obtained during decay of the 99mTc.
Statistics Reproducibility of DXA measurements was calculated as coefficient of variation (CV) and 95% confidence intervals (95% CIs). Anthropometric variables were compared between patients and controls using a 2-sided Student’s t-test for each gender. The correlation between activity in MBq or dose rate in mSv/h and the change in BMD, bone mineral content (BMC), fat, and fat-free mass were analyzed using linear regression, and the square of the correlation coefficient (R, Pearson) was calculated. A p value less than 0.05 was considered significant.
Results There were no significant differences between control and patient groups with regard to anthropometric and body composition variables, except for female patients being significantly leaner than the controls (Table 1).
Table 1 Anthropometric and Body Composition Variables for Patients and Controls
Variables Age (yr) Height (cm) Body mass (kg) BMD (g/cm2) BMC (kg) Fat (kg) Fat-free mass (kg)
Female patients (n 5 12), mean 1 SD 49.9 19.1 167 7 64.8 12.8 1.15 0.14 2.52 0.55 20.3 9.9 41.9 6.4
p
Female controls (n 5 12), mean 1 SD
Male patients (n 5 15), mean 1 SD
p
Male controls (n 5 28), mean 1 SD
n.s. n.s. n.s. n.s. n.s. 0.006 n.s.
45.5 14.7 170 9 74.9 16.2 1.27 0.31 2.64 0.53 26.9 11.7 45.3 8.2
55.1 21.5 176 8 82.7 12.5 1.20 0.07 3.04 0.36 23.8 10.8 55.8 6.7
n.s. n.s. n.s. n.s. n.s. n.s. n.s.
46.3 21.3 180 7 77.8 8.4 1.28 0.20 3.25 0.58 16.2 6.5 55.8 7.9
Abbr: BMC, bone mineral content; BMD, bone mineral density; n.s., not significant; SD, standard deviation. Journal of Clinical Densitometry: Assessment & Management of Musculoskeletal Health
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Variables (N 5 40)
Mean 1 SD
CV
Body mass (kg) BMD (g/cm2) BMC (kg) Fat (kg) Fat-free mass (kg)
77.2 11.2 1.28 0.23 3.07 0.62 19.4 9.5 52.6 9.2
1.1 1.5 1.7 2.5 1.0
Mean difference SE of the mean difference
95% CI of mean difference
0.06 0.14 0.002 0.003 0.002 0.008 0.025 0.077 0.049 0.084
1.68 0.037 0.014 0.13 0.22
to to to to to
1.79 0.041 0.019 0.18 0.12
Note: CV is calculated as SD/mean in percentage. Mean difference, SE of the mean difference, and 95% confidence intervals or limits of agreement are calculated according to the study by Altman (10). Abbr: BMC, bone mineral content; BMD, bone mineral density; CI, confidence interval; CV, coefficient of variation; DXA, dual-energy X-ray absorptiometry; SD, standard deviation; SE, standard error.
CV for repeated DXA scans varied from 1.0% to 2.5% with fat-free mass having the best reproducibility and fat mass the poorest of the 5 variables shown in Table 2. The results of repeated DXA scans of patients and wholebody phantom are presented in Tables 3 and 4, respectively. For both patient and phantom scans, there were significant correlations between changes in all DXA variables and increasing radiation from the patient/phantom with the exception of bone area, which did not change significantly on phantom scans. Fat-free mass increased, whereas fat mass, BMD, and BMC decreased with increasing radiation from the patient or phantom. The change in BMD and body composition of the patients depending on the measured dose rate is shown in Figs. 1 and 2, respectively. We have calculated upper dose rate limits for the measurement of BMD at 0.77 mSv/h and body composition at 0.21 mSv/h (dose rate measured at a distance of 1 m from the patient). These limits are based on the intercept between the linear regression line from the patient measurements and the 95% CI from the control group.
Discussion This study underlines that g-radiation from injected 99mTc tracers affects the results of whole-body DXA scans performed
on a KEF scanner. As displayed in Figs. 1 and 2, there is some variability in the measured DXA parameters. A suspected cause for this could be measurement inaccuracy of the survey meter used to measure dose rate from the patients. The variability regarding the measurement of body composition could also be caused by unregistered fluid/food intake between the 2 DXA scans. The results from both patient and phantom studies reveal a significant dose-related increase in fat-free mass and a corresponding decrease in fat mass, BMC, and BMD following the injection of various 99mTc tracers. The change in body composition, particularly, is substantial even at relatively low measured dose rates. A list of expected dose rates after various nuclear medicine studies can be found in the textbook by Ell and Gambhir (11). The confounding effect of 99mTc on the measurement of body composition is in accordance with the results of Rosenthall (7), who reported a decrease in measured fat mass following 99mTc injection. A similar study by Sala et al (8) found no significant difference in body composition measured by DXA. Sala et al only included 4 patients (children aged 3e18 yr) in whom the DXA scan was performed using a KEF scanner. The limited number of patients could explain why the results showed no significant change in body composition.
Table 3 Mean Values Without a Radioactive Tracer in the Patient and the Effect of Radioactivity From the Patient on Bone Mass, Body Composition, and Bone Area Expressed by Slope and y-Axis Intercept for the Patients Variables (N 5 27) Body mass BMD BMC Fat Fat-free mass Bone area
Mean 1 SD
SI unit
Slope
74.7 15.3 1.18 0.11 2.81 0.52 22.3 10.4 49.7 9.6 2369 290
kg g/cm2 kg kg kg cm2
0.508 0.014 0.058 1.43 0.983 21.3
SI unit
Intercept
SI unit
R2
p
kg/mSv/h g/cm2/mSv/h kg/mSv/h kg/mSv/h kg/mSv/h cm2/mSv/h
0.377 0.007 0.007 0.18 0.189 7.92
kg g/cm2 kg kg kg cm2
0.64 0.77 0.59 0.74 0.69 0.26
!0.001 !0.001 !0.001 !0.001 !0.001 !0.01
Abbr: BMC, bone mineral content; BMD, bone mineral density; SD, standard deviation. Journal of Clinical Densitometry: Assessment & Management of Musculoskeletal Health
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Table 4 Mean Values Without a Radioactive Tracer and the Effect of Radioactivity in a Bladder Phantom on Bone Mass, Body Composition, and Bone Area Expressed by Slope and y-Axis Intercept for the Whole-Body Phantom Scans Variables Body mass BMD BMC Fat Fat-free mass Bone area
Mean 1 SD
SI unit
27.9 0.01 1.29 0.01 699 5 9.75 0.06 18.1 0.06 542 6
kg g/cm2 g kg kg cm2
Slope 0.2 0.003 2.46 0.72 0.76 0.33
SI unit
Intercept
SI unit
R2
p
kg/mSv/h g/cm2/mSv/h g/mSv/h kg/mSv/h kg/mSv/h cm2/mSv/h
0.015 0.0017 702 0.11 0.043 537
kg g/cm2 g kg kg cm2
0.98 0.32 0.12 0.97 0.98 0.005
!0.001 !0.001 !0.01 !0.001 !0.001 n.s.
Abbr: BMC, bone mineral content; BMD, bone mineral density; n.s., not significant; SD, standard deviation.
Similar to several other studies using a KEF DXA scanner, we find that the presence of 99mTc tracers reduces measured BMD of the patient or phantom (4e7,9). This is most likely due to the Compton scattered g-radiation from 99mTc being detected as non-attenuated X-rays by the detector of the DXA scanner, thereby causing erroneous estimation of the distribution of soft and bone tissues. Our results show significantly reduced measured bone area in the patient group after the injection of 99mTc tracers. However, the measured phantom bone area is unaffected by the 99mTc tracer. This discrepancy can be caused by the structural differences between human and phantom bones. Human bones are of irregular shape, and therefore more complicated to outline, as opposed to the bones of the phantom, which have more clearly defined edges. Evidence suggests that the influence of 99mTc tracers is dependent on the DXA system. In contrast to the KEF scanner used in the present study, scanners using PPS technology do not seem to be affected by the presence of radioactive isotopes (3,6,8). The KEF scanners contain a rare earth metal filter (e.g., cerium), which creates 2 energy peaks at approx 40 and 70 keV from a polyenergetic X-ray beam. The PPS
system uses alternating pulses applied to the X-ray tube, in which the X-ray beam is switched between 70 and 140 keV (12,13). Opposed to the technology of the KEF scanners, the high and low energy beams are detected sequentially instead of simultaneously. This enables the PPS system to adjust for background noise and beam hardening via a calibration process, making the scanner less susceptible to be affected by the g-radiation from a radioactive tracer. In conclusion, this study demonstrates that in both phantom and patient measurements a whole-body DXA scan performed by a KEF scanner will produce erroneous results when a radioactive 99mTc tracer is present. Even relatively low levels of radiation will result in falsely increased fatfree mass and decreased fat mass, BMC, and BMD. Assessment of body composition is prone to larger errors due to radiation than bone density measurements. DXA measurements should preferably be performed before nuclear medicine procedures, if requested in close-time proximity, when using KEF scanners. Otherwise, an interval of at least 24e48 h after a patient had a 99mTc injection is recommendable before performing a DXA scan depending on
Fig. 1. Change in bone mineral density (g/cm2) of the patients depending on the measured dose rate (mSv/h). The horizontal truncated lines represent the 95% confidence interval for repeated patient measurements without prior administration of a radioactive tracer.
Fig. 2. Change in fat mass (triangles) and fat-free mass (squares) of the patients depending on the measured dose rate (mSv/h). The horizontal truncated lines represent the 95% confidence interval for repeated patient measurements without prior administration of a radioactive tracer.
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Tc on DXA Measurement
the injected dose and biological half-life of the tracer. Measurement of radiation from the patient before a DXA scan on the suspicion of recent radioactive tracer administration is recommendable, and radiation should not exceed the limits stated in this report. Previous studies suggest that this precaution may not be required when DXA scanning is performed with PPS technology.
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6. 7. 8.
References 1. Cummings SR, Black DM, Nevitt MC, et al. 1993 Bone density at various sites for prediction of hip fractures. The Study of Osteoporosis Fractures Research Group. Lancet 341:72e75. 2. Albanese CV, Diessel E, Genant HK. 2003 Clinical applications of body composition measurements using DXA. J Clin Densitom 6(2):75e85. Summer. 3. Campbell A, McCarthy M, Blake M, Roff G. 2005 Effect of 99m Tc-MDP administration on dual-energy X-ray absorptiometry bone mineral density measurements. J Clin Densitom 8: 14e17. doi:JCD:8:1:014. 4. Chan PS, Binkley NC, Lalande BM, Young S, Shaker JL. 2004 Artifactual reduction in bone density as a result of technetium-99m MDP for bone scanning: report of two cases. J Clin Densitom 7:457e458. 5. McKiernan FE, Hocking J, Cournoyer S. 2006 Antecedent 99m Tc-MDP and 99mTc-sestamibi administration corrupts bone
9.
10. 11. 12. 13.
mineral density measured by DXA. J Clin Densitom 9: 164e166. doi:S1094-6950. Mueller B, O’Connor MK. 2002 Effects of radioisotopes on the accuracy of dual-energy X-ray absorptiometry for bone densitometry. J Clin Densitom 5:283e287. Rosenthall L. 1992 Estimation of the effect of a preinjection of 99m Tc MDP on lumbar spine bone mineral density determinations. Clin Nucl Med 17:195e197. Sala A, Webber C, Halton J. 2006 Effect of diagnostic radioisotopes and radiographic contrast media on measurements of lumbar spine bone mineral density and body composition by dual-energy X-ray absorptiometry. J Clin Densitom 9(1): 91e96. Gumuser G, Parlak Y, Topal G, et al. 2009 Effects of 99mTcMIBI and 99mTc-MDP administration on dual-energy X-ray absorptiometry bone mineral density measurements. Nucl Med Commun 30(6):445e448. Altman D. 1990 Practical statistics for medical research. London: Chapman & Hall/CRC Texts in Statistical Science. Ell PJ, Gambhir SS. 2004 Radiation protection and dosimetry in clinical practice. In: Nuclear medicine in clinical diagnosis and treatment. 3rd ed. Edinburgh: Churchill Livingstone, 1888e1889. Bonnick SL. 2009 Bone densitometry in clinical practice: application and interpretation. 3rd ed. New York: Humana Press. Pietrobelli A, Formica C, Wang Z, Heymsfield SB. 1996 Dualenergy X-ray absorptiometry body composition model: review of physical concepts. Am J Physiol 271(6 pt 1):E941eE951.
Journal of Clinical Densitometry: Assessment & Management of Musculoskeletal Health
Volume 16, 2013
Original Article
The Effect of 99mTc on Dual-Energy X-Ray Absorptiometry Measurement of Body Composition and Bone Mineral Density Marie Øbro Fosbøl,* Anders Dupont, Louise Alslev, and Bo Zerahn Department of Clinical Physiology and Nuclear Medicine, Herlev Hospital, Denmark
Abstract Whether the g-emission by radioisotopes influences the outcome of dual-energy X-ray absorptiometry (DXA) measurements is not fully elucidated. The aim of this study was to evaluate the effect of antecedent administration of 99mTc on DXA measurements regarding body composition and bone mineral density (BMD) using a K-edge filter scanner. The phantom measurements were performed by placing a urinary bladder phantom containing 40 mL of radioisotope solution on the pelvic region of a whole-body phantom. Twenty-seven patients attending our department for a routine examination involving the administration of a tracer marked with 99mTc were included. The patients underwent a whole-body DXA scan before and within 2 h after tracer injection using a GE/Lunar Prodigy scanner. Control scans were performed on 40 volunteers, who had not received any radioactive tracer. In both phantom and patient measurements, we found a significant dose-related decrease in fat mass and BMD and a corresponding increase in fat-free mass ( p ! 0.001). Based on the linear regression analysis, we suggest upper dose limits for the measurement of BMD at 0.77 mSv/h and body composition at 0.21 mSv/h (dose rate measured at a distance of 1 m from the patient). Caution should be taken when interpreting the results of DXA scans performed in close temporal proximity to procedures involving the administration of 99mTc. Key Words: Body composition; bone mineral density; dual-energy X-ray absorptiometry; gamma radiation; radiopharmaceuticals.
BMD has been investigated in several studies (3e9). These have shown inconsistent results regarding the confounding effect of tracers marked with 99mTc on DXA measurement of BMD. Evidence suggests that the influence of the radioactive tracer is dependent on the DXA system. No significant effect of 99mTc on BMD has been found in studies using scanners with the pulsed power source (PPS) technology (3,6,8). In contrast, 3 studies using K-edge filter (KEF) scanners have shown a significant decrease in measured BMD following the injection of a 99mTc tracer (5,7,9). The influence of radioactive tracers on DXA measurement of body composition is not fully disclosed. Rosenthall (7) measured fat mass in 15 patients before and after the injection of 99mTc methylene diphosphonate using a KEF DXA scanner and found a significant decrease in fat mass. Sala et al (8) investigated the effect of 99mTc on DXA measurement of body composition in children (aged 3e18 yr). DXA scans were performed using either a PPS or a KEF scanner and no significant change in body composition or BMD was detected.
Introduction Dual-energy X-ray absorptiometry (DXA) is widely used to diagnose osteoporosis and monitor the development of bone mineral density (BMD) during therapy (1). DXA measurement of body composition has numerous clinical applications including the assessment of patients with nutritional disorders or gastrointestinal disease (2). Whenever a DXA scan is requested in close-time proximity to a nuclear medicine procedure, it is important to know whether the g-rays emitted by radiopharmaceuticals interfere with the detection of the X-rays used in the DXA systems. A relation between g-radiation emitted from 99mTc and DXA measurement of
Received 02/17/12; Revised 05/14/12; Accepted 05/17/12. *Address correspondence to: Marie Øbro Fosbøl, MD, Department of Clinical Physiology and Nuclear Medicine, Herlev Hospital, Denmark. E-mail: [email protected]
297
298
Fosbøl et al.
The aim of this study was to determine how tracers marked with 99mTc affect BMD and body composition measurements on human beings as well as a whole-body phantom on a KEF system. Our secondary aim was to determine a dose limit of g-radiation from 99mTc below which a DXA scanner will produce reliable results.
Methods and Materials Patient Measurements This is a prospective, longitudinal, single cohort study of 27 patients (12 women and 15 men) undergoing scheduled nuclear medicine procedures (renography [N 5 13], bone scintigraphy [N 5 10], radionuclide ventriculography [N 5 2], lymph drainage scintigraphy [N 5 1], and myocardial perfusion imaging [N 5 1]). All were included after acquiring written informed consent. The exclusion criteria were impaired renal function, impaired cognitive function, pregnancy, body weight more than 135 kg, or metal implants from major orthopedic surgery (hip and knee arthroplasties and femoral or tibial osteosyntheses). The dose of 99mTc ranged from 50 to 800 MBq. Wholebody DXA was performed before and after the administration of 99mTc measuring BMD and body composition using a Lunar Prodigy scanner (GE Lunar, Madison, WI). Radiation dose rate was measured at a distance of 1 m at the level of the urinary bladder before and after each DXA scan using a Rados RDS-200 Universal Survey Meter (Mirion Technologies, San Ramon, CA). The average of the 2 readings was used in the data analysis. The time interval from the injection of the tracer to the second DXA scan varied from 5 min to 2 h depending on the procedure used. Patients were instructed to refrain from food intake, and all fluid input and output were measured between the first and second DXA scan. The effective radiation exposure per whole-body DXA scan was approx 0.37 mSv (2). All patients were supine positioned in exactly the same manner at both DXA scans according to the manufacturers’ manual. Reproducibility of the whole-body DXA scan was
determined on 40 volunteers who were scanned sequentially with full repositioning and no administration of radioactive tracers between measurements. The study was approved by the regional committee on biomedical research ethics (study number H-A-2009-003).
Whole-Body Phantom Measurements As a preliminary study, we conducted measurements on a whole-body phantom. A urinary bladder phantom containing 40 mL of radioisotope solution was placed on the pelvic region of a whole-body phantom (WB Phantom, serial no. WB 1008; Hologic, Inc., Bedford, MA) after which a series of DXA scans were performed and analyzed. The range of 99m Tc activity evaluated in this study was 5e205 MBq (68 sequential measurements). Sixteen control scans were performed on the whole-body phantom on 3 different days without the presence of a radioactive isotope. Mean values are based on the control scans without the presence of a radioactive isotope, whereas slope, intercept, and correlation coefficient are based on the 68 sequential scans obtained during decay of the 99mTc.
Statistics Reproducibility of DXA measurements was calculated as coefficient of variation (CV) and 95% confidence intervals (95% CIs). Anthropometric variables were compared between patients and controls using a 2-sided Student’s t-test for each gender. The correlation between activity in MBq or dose rate in mSv/h and the change in BMD, bone mineral content (BMC), fat, and fat-free mass were analyzed using linear regression, and the square of the correlation coefficient (R, Pearson) was calculated. A p value less than 0.05 was considered significant.
Results There were no significant differences between control and patient groups with regard to anthropometric and body composition variables, except for female patients being significantly leaner than the controls (Table 1).
Table 1 Anthropometric and Body Composition Variables for Patients and Controls
Variables Age (yr) Height (cm) Body mass (kg) BMD (g/cm2) BMC (kg) Fat (kg) Fat-free mass (kg)
Female patients (n 5 12), mean 1 SD 49.9 19.1 167 7 64.8 12.8 1.15 0.14 2.52 0.55 20.3 9.9 41.9 6.4
p
Female controls (n 5 12), mean 1 SD
Male patients (n 5 15), mean 1 SD
p
Male controls (n 5 28), mean 1 SD
n.s. n.s. n.s. n.s. n.s. 0.006 n.s.
45.5 14.7 170 9 74.9 16.2 1.27 0.31 2.64 0.53 26.9 11.7 45.3 8.2
55.1 21.5 176 8 82.7 12.5 1.20 0.07 3.04 0.36 23.8 10.8 55.8 6.7
n.s. n.s. n.s. n.s. n.s. n.s. n.s.
46.3 21.3 180 7 77.8 8.4 1.28 0.20 3.25 0.58 16.2 6.5 55.8 7.9
Abbr: BMC, bone mineral content; BMD, bone mineral density; n.s., not significant; SD, standard deviation. Journal of Clinical Densitometry: Assessment & Management of Musculoskeletal Health
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Variables (N 5 40)
Mean 1 SD
CV
Body mass (kg) BMD (g/cm2) BMC (kg) Fat (kg) Fat-free mass (kg)
77.2 11.2 1.28 0.23 3.07 0.62 19.4 9.5 52.6 9.2
1.1 1.5 1.7 2.5 1.0
Mean difference SE of the mean difference
95% CI of mean difference
0.06 0.14 0.002 0.003 0.002 0.008 0.025 0.077 0.049 0.084
1.68 0.037 0.014 0.13 0.22
to to to to to
1.79 0.041 0.019 0.18 0.12
Note: CV is calculated as SD/mean in percentage. Mean difference, SE of the mean difference, and 95% confidence intervals or limits of agreement are calculated according to the study by Altman (10). Abbr: BMC, bone mineral content; BMD, bone mineral density; CI, confidence interval; CV, coefficient of variation; DXA, dual-energy X-ray absorptiometry; SD, standard deviation; SE, standard error.
CV for repeated DXA scans varied from 1.0% to 2.5% with fat-free mass having the best reproducibility and fat mass the poorest of the 5 variables shown in Table 2. The results of repeated DXA scans of patients and wholebody phantom are presented in Tables 3 and 4, respectively. For both patient and phantom scans, there were significant correlations between changes in all DXA variables and increasing radiation from the patient/phantom with the exception of bone area, which did not change significantly on phantom scans. Fat-free mass increased, whereas fat mass, BMD, and BMC decreased with increasing radiation from the patient or phantom. The change in BMD and body composition of the patients depending on the measured dose rate is shown in Figs. 1 and 2, respectively. We have calculated upper dose rate limits for the measurement of BMD at 0.77 mSv/h and body composition at 0.21 mSv/h (dose rate measured at a distance of 1 m from the patient). These limits are based on the intercept between the linear regression line from the patient measurements and the 95% CI from the control group.
Discussion This study underlines that g-radiation from injected 99mTc tracers affects the results of whole-body DXA scans performed
on a KEF scanner. As displayed in Figs. 1 and 2, there is some variability in the measured DXA parameters. A suspected cause for this could be measurement inaccuracy of the survey meter used to measure dose rate from the patients. The variability regarding the measurement of body composition could also be caused by unregistered fluid/food intake between the 2 DXA scans. The results from both patient and phantom studies reveal a significant dose-related increase in fat-free mass and a corresponding decrease in fat mass, BMC, and BMD following the injection of various 99mTc tracers. The change in body composition, particularly, is substantial even at relatively low measured dose rates. A list of expected dose rates after various nuclear medicine studies can be found in the textbook by Ell and Gambhir (11). The confounding effect of 99mTc on the measurement of body composition is in accordance with the results of Rosenthall (7), who reported a decrease in measured fat mass following 99mTc injection. A similar study by Sala et al (8) found no significant difference in body composition measured by DXA. Sala et al only included 4 patients (children aged 3e18 yr) in whom the DXA scan was performed using a KEF scanner. The limited number of patients could explain why the results showed no significant change in body composition.
Table 3 Mean Values Without a Radioactive Tracer in the Patient and the Effect of Radioactivity From the Patient on Bone Mass, Body Composition, and Bone Area Expressed by Slope and y-Axis Intercept for the Patients Variables (N 5 27) Body mass BMD BMC Fat Fat-free mass Bone area
Mean 1 SD
SI unit
Slope
74.7 15.3 1.18 0.11 2.81 0.52 22.3 10.4 49.7 9.6 2369 290
kg g/cm2 kg kg kg cm2
0.508 0.014 0.058 1.43 0.983 21.3
SI unit
Intercept
SI unit
R2
p
kg/mSv/h g/cm2/mSv/h kg/mSv/h kg/mSv/h kg/mSv/h cm2/mSv/h
0.377 0.007 0.007 0.18 0.189 7.92
kg g/cm2 kg kg kg cm2
0.64 0.77 0.59 0.74 0.69 0.26
!0.001 !0.001 !0.001 !0.001 !0.001 !0.01
Abbr: BMC, bone mineral content; BMD, bone mineral density; SD, standard deviation. Journal of Clinical Densitometry: Assessment & Management of Musculoskeletal Health
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Fosbøl et al.
Table 4 Mean Values Without a Radioactive Tracer and the Effect of Radioactivity in a Bladder Phantom on Bone Mass, Body Composition, and Bone Area Expressed by Slope and y-Axis Intercept for the Whole-Body Phantom Scans Variables Body mass BMD BMC Fat Fat-free mass Bone area
Mean 1 SD
SI unit
27.9 0.01 1.29 0.01 699 5 9.75 0.06 18.1 0.06 542 6
kg g/cm2 g kg kg cm2
Slope 0.2 0.003 2.46 0.72 0.76 0.33
SI unit
Intercept
SI unit
R2
p
kg/mSv/h g/cm2/mSv/h g/mSv/h kg/mSv/h kg/mSv/h cm2/mSv/h
0.015 0.0017 702 0.11 0.043 537
kg g/cm2 g kg kg cm2
0.98 0.32 0.12 0.97 0.98 0.005
!0.001 !0.001 !0.01 !0.001 !0.001 n.s.
Abbr: BMC, bone mineral content; BMD, bone mineral density; n.s., not significant; SD, standard deviation.
Similar to several other studies using a KEF DXA scanner, we find that the presence of 99mTc tracers reduces measured BMD of the patient or phantom (4e7,9). This is most likely due to the Compton scattered g-radiation from 99mTc being detected as non-attenuated X-rays by the detector of the DXA scanner, thereby causing erroneous estimation of the distribution of soft and bone tissues. Our results show significantly reduced measured bone area in the patient group after the injection of 99mTc tracers. However, the measured phantom bone area is unaffected by the 99mTc tracer. This discrepancy can be caused by the structural differences between human and phantom bones. Human bones are of irregular shape, and therefore more complicated to outline, as opposed to the bones of the phantom, which have more clearly defined edges. Evidence suggests that the influence of 99mTc tracers is dependent on the DXA system. In contrast to the KEF scanner used in the present study, scanners using PPS technology do not seem to be affected by the presence of radioactive isotopes (3,6,8). The KEF scanners contain a rare earth metal filter (e.g., cerium), which creates 2 energy peaks at approx 40 and 70 keV from a polyenergetic X-ray beam. The PPS
system uses alternating pulses applied to the X-ray tube, in which the X-ray beam is switched between 70 and 140 keV (12,13). Opposed to the technology of the KEF scanners, the high and low energy beams are detected sequentially instead of simultaneously. This enables the PPS system to adjust for background noise and beam hardening via a calibration process, making the scanner less susceptible to be affected by the g-radiation from a radioactive tracer. In conclusion, this study demonstrates that in both phantom and patient measurements a whole-body DXA scan performed by a KEF scanner will produce erroneous results when a radioactive 99mTc tracer is present. Even relatively low levels of radiation will result in falsely increased fatfree mass and decreased fat mass, BMC, and BMD. Assessment of body composition is prone to larger errors due to radiation than bone density measurements. DXA measurements should preferably be performed before nuclear medicine procedures, if requested in close-time proximity, when using KEF scanners. Otherwise, an interval of at least 24e48 h after a patient had a 99mTc injection is recommendable before performing a DXA scan depending on
Fig. 1. Change in bone mineral density (g/cm2) of the patients depending on the measured dose rate (mSv/h). The horizontal truncated lines represent the 95% confidence interval for repeated patient measurements without prior administration of a radioactive tracer.
Fig. 2. Change in fat mass (triangles) and fat-free mass (squares) of the patients depending on the measured dose rate (mSv/h). The horizontal truncated lines represent the 95% confidence interval for repeated patient measurements without prior administration of a radioactive tracer.
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The Effect of
99m
Tc on DXA Measurement
the injected dose and biological half-life of the tracer. Measurement of radiation from the patient before a DXA scan on the suspicion of recent radioactive tracer administration is recommendable, and radiation should not exceed the limits stated in this report. Previous studies suggest that this precaution may not be required when DXA scanning is performed with PPS technology.
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6. 7. 8.
References 1. Cummings SR, Black DM, Nevitt MC, et al. 1993 Bone density at various sites for prediction of hip fractures. The Study of Osteoporosis Fractures Research Group. Lancet 341:72e75. 2. Albanese CV, Diessel E, Genant HK. 2003 Clinical applications of body composition measurements using DXA. J Clin Densitom 6(2):75e85. Summer. 3. Campbell A, McCarthy M, Blake M, Roff G. 2005 Effect of 99m Tc-MDP administration on dual-energy X-ray absorptiometry bone mineral density measurements. J Clin Densitom 8: 14e17. doi:JCD:8:1:014. 4. Chan PS, Binkley NC, Lalande BM, Young S, Shaker JL. 2004 Artifactual reduction in bone density as a result of technetium-99m MDP for bone scanning: report of two cases. J Clin Densitom 7:457e458. 5. McKiernan FE, Hocking J, Cournoyer S. 2006 Antecedent 99m Tc-MDP and 99mTc-sestamibi administration corrupts bone
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mineral density measured by DXA. J Clin Densitom 9: 164e166. doi:S1094-6950. Mueller B, O’Connor MK. 2002 Effects of radioisotopes on the accuracy of dual-energy X-ray absorptiometry for bone densitometry. J Clin Densitom 5:283e287. Rosenthall L. 1992 Estimation of the effect of a preinjection of 99m Tc MDP on lumbar spine bone mineral density determinations. Clin Nucl Med 17:195e197. Sala A, Webber C, Halton J. 2006 Effect of diagnostic radioisotopes and radiographic contrast media on measurements of lumbar spine bone mineral density and body composition by dual-energy X-ray absorptiometry. J Clin Densitom 9(1): 91e96. Gumuser G, Parlak Y, Topal G, et al. 2009 Effects of 99mTcMIBI and 99mTc-MDP administration on dual-energy X-ray absorptiometry bone mineral density measurements. Nucl Med Commun 30(6):445e448. Altman D. 1990 Practical statistics for medical research. London: Chapman & Hall/CRC Texts in Statistical Science. Ell PJ, Gambhir SS. 2004 Radiation protection and dosimetry in clinical practice. In: Nuclear medicine in clinical diagnosis and treatment. 3rd ed. Edinburgh: Churchill Livingstone, 1888e1889. Bonnick SL. 2009 Bone densitometry in clinical practice: application and interpretation. 3rd ed. New York: Humana Press. Pietrobelli A, Formica C, Wang Z, Heymsfield SB. 1996 Dualenergy X-ray absorptiometry body composition model: review of physical concepts. Am J Physiol 271(6 pt 1):E941eE951.
Journal of Clinical Densitometry: Assessment & Management of Musculoskeletal Health
Volume 16, 2013