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Calcium Supplement Ingestion May Alter Lumbar Spine Bone Mineral Density Measurement
Journal of Clinical Densitometry, vol. 9, no. 2, 159–163, 2006 Ó Copyright 2006 by The International Society for Clinical Densitometry 1094-6950/06/9:159–163/$32.00 DOI: 10.1016/j.jocd.2006.01.002
Original Article
Calcium Supplement Ingestion May Alter Lumbar Spine Bone Mineral Density Measurement Diane Krueger,* Mary Checovich, Dessa Gemar, Xiaodan Wei, and Neil Binkley University of Wisconsin Osteoporosis Clinical Center & Research Program, Madison, WI
Abstract Densitometry centers commonly request patients abstain from ingesting calcium supplements prior to dualenergy X-ray absorptiometry (DXA) examination to avoid interference with bone mineral density (BMD) measurement. However, it is not clear that this practice is necessary. This study assessed the impact of recent calcium supplement intake on lumbar spine BMD measurement. The phase 1 experiment demonstrated BMD differences when placing a supplement over various areas of two encapsulated phantoms. To determine whether these results were clinically relevant, the phase 2 study enrolled 36 subjects who received spine scans before and after random assignment to ingest one Citracal, OsCal or People’s Choice tablet providing 315, 500, and 600 mg of elemental calcium, respectively. The phase 3 study evaluated 15 subjects that had three spine scans with repositioning between to establish BMD precision, and then ingested a calcium carbonate tablet. Post-dosing scans were performed 15 and 30 minutes after tablet ingestion. The difference in L1–L4 BMD on subsequent scans was compared with the study derived least significant change (LSC) of 0.028 g/cm2. In phase 2, L1–L4 BMD changes outside the LSC occurred in 36% of subjects with 47% having visualized tablets. Similarly, 33% of the phase 3 subjects demonstrated changes outside the LSC after calcium ingestion and 53% of the subjects in phase 3 had tablets visualized. Visualization of calcium tablets was not associated with BMD changes. In conclusion, calcium tablet intake may affect measured L1–L4 BMD within 30 minutes of ingestion. As such, it is appropriate to request patients abstain from calcium tablet ingestion prior to a spine DXA examination. Key Words: Artifact; bone mineral density; calcium supplements; DXA.
affects DXA measured results (12,13). It is widely assumed that calcium tablet ingestion would have a similar impact, thereby confounding spine DXA results. As calcium tablets may be an avoidable artifact, many DXA centers and the American College of Radiology/Radiological Society of North America routinely advise against their ingestion for 24 hours prior to scan performance (14). Interestingly, these recommendations to avoid calcium tablets prior to DXA scanning do not extend to other medications or supplements and ex vivo data findings presented in abstract form suggest that many tablets may alter phantom BMD measurement (15). As patients and providers frequently question the need to abstain from calcium ingestion, and few studies have evaluated this issue, we investigated the effect of different calcium supplements on DXA-measured spine BMD using phantoms and humans.
Introduction Optimal bone density measurement using DXA demands minimization of artifacts (1). Many of these are internal and can not be removed, such as surgical hardware, osteoarthritis, calcified aortas, or implants (2–8). However many are external, such as metal objects (e.g., zippers) or buttons made of shells (9,10), and are routinely removed. Additionally, fat panniculi, when present, are retracted (11). A third category of temporary internal artifact also exists. Technetium and barium that has not cleared the gastrointestinal tract adversely Received: 10/12/05; Revised: 12/26/05; Accepted: 01/16/06. *Address correspondence to: Diane Krueger, BS, CDT, University of Wisconsin Osteoporosis Research Program, 2870 University Avenue, Suite 100, Madison, WI 53705. E-mail: [email protected]
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Subjects and Methods Phase 1: Calcium Supplements on Phantoms Acrylic encapsulated spine phantoms from GE Healthcare Lunar (Madison, WI) and Hologic (Bedford, MA) were utilized. Each phantom was scanned alone, then subsequently with a single tablet of 5 different calcium supplements overlaying phantom ‘‘soft tissue’’ and again with the supplements overlaying ‘‘bone.’’ The calcium supplements tested in this phase of the study were as follows: Citracal (315 mg; calcium citrate; Mission Pharmacal, St. Louis, MO); OsCal (500 mg; calcium carbonate; GlaxoSmithKline, Moon Township, PA); People’s Choice (600 mg; calcium carbonate; Dollar Tree Stores Inc., Norfolk, VA); Tums Smooth Dissolve (300 mg; calcium carbonate; GlaxoSmithKline, Brentford, UK) and Viactiv (500 mg; calcium carbonate; McNeil-PPC Inc., Fort Washington, PA). The 3 combinations (no calcium present, calcium supplement placed to overlay bone, and calcium supplement placed to overlay soft tissue) were each scanned 3 times. The calcium tablet, but not the phantom, was repositioned between each scan.
Phase 2: Human Calcium Supplement Ingestion Lumbar spine DXA scans were performed on 36 adult volunteers. Subsequently, all participants were randomly assigned to receive one tablet of Citracal, OsCal, or People’s Choice at the doses noted in phase 1. These supplements were chosen from the 5 to represent brand name calcium citrate and carbonate supplements, Citracal and OsCal, respectively, and a low cost supplement that consisted of calcium carbonate. In addition, supplement tablets were chosen over the chewables for better visualization. Lumbar spine scans were repeated 15 and 30 min subsequent to calcium ingestion. In summary, this study phase included 3 groups (n 5 12 in each group who had 3 scans performed; baseline: 15 min and 30 min).
Phase 3: Precision Assessment Followed by Calcium Ingestion A lumbar spine DXA precision assessment was performed following an approach recommended by the International Society for Clinical Densitometry (ISCD) (16). Briefly, 3 lumbar spine scans were performed with repositioning between each scan using 15 adult volunteers. Immediately following the third scan, one 600 mg tablet of People’s Choice calcium was taken, as this was most commonly visualized, and spine scans were repeated 15 and 30 min later. Study phases 2 and 3 were reviewed and approved by the University of Wisconsin Health Sciences Human Subjects Committee. All participants provided written informed consent prior to any study procedure being performed.
Densitometry Data Acquisition and Analysis The DXA scans for all study phases were performed using a single GE Healthcare Lunar Prodigy densitometer (Madison, WI) with software version 6.7 or 9.2. Two ISCDcertified technologists performed all scans in phases 1 and 2, and one technologist performed all scans in phase 3. Initial Journal of Clinical Densitometry
Krueger et al. phase 2 scans were autoanalyzed, only correcting intervertebral marker placement. This approach was taken to observe whether or not tablet related changes in soft tissue density would impact the software’s ability to detect bone edges. Point typing was altered in phase 3 when appropriate as is the case in clinical precision assessments. The copy feature was used for all post baseline scans in all 3 study phases. Two ISCD-certified technologists and one ISCD-certified clinician, without knowledge of BMD change, independently assessed tablet visualization on a printed DXA image. When disagreement regarding tablet visualization occurred, group consensus was reached.
Data/Statistical Analyses Dual-energy X-ray absorptiometry precision, and therefore, LSC was calculated using the ISCD precision calculator downloaded from the website (www.ISCD.org) (16). Phantom precision was determined by calculating phantom values from 60 consecutive phantom acquisition days. Using this approach, the LSC for the GE Healthcare Lunar and Hologic acrylic phantoms was 0.011 and 0.019 grams/cm2, respectively. In our human volunteer sample (phase 3), the L1–L4 BMD LSC was 0.028 grams/cm2. Group demographic data in phase 2 and frequency of tablet visualization in phases 2 and 3 were evaluated by the paired t test. To more clearly depict the impact of calcium supplement ingestion on follow-up BMD measurements, all changes from baseline (both BMD increases and decreases) were changed to positive values and the mean deviation from baseline was reported as ‘‘delta BMD.’’ The BMD variability in phase 3 was evaluated using the equality of variances F test. All analyses were performed using Statview software (Abacus, Cary, NC) or Analyze-It (Leeds, UK).
Results Phase 1: Calcium Supplements on Phantoms A statistically significant increase ( p ! 0.01) in L1–L4 BMD was demonstrated in the majority of cases (70%) when the calcium supplement tablet was placed over bone (Fig. 1). Similarly, a statistically significant difference ( p ! 0.01) in L1–L4 BMD was observed 50% of the time when the tablet was placed over soft tissue. Although significant and often outside the phantom LSC (0.011/0.019 g/cm2), none of these differences exceeded the clinical LSC of 0.028 g/cm2. The soft tissue composition differed between these two phantoms with the GE Lunar phantom being read as containing w36% fat and the Hologic phantom containing w75% fat.
Phase 2: Human Calcium Supplement Ingestion Demographics Thirty-three women and 3 men participated in this study phase. Their mean age was 66 yr (range: 36.4–84.2 yr), their body mass index was 26 kg/m2 (range: 18.1–42.2 kg/m2), their L1–L4 BMD scores were 1.064 g/cm2 (range: 0.619– 1.504 g/cm2), and their L1–L4 T-scores were 20.92 (range: 24.6 to 2.7). Applying the World Health Organization (WHO) classification system to lumbar spine BMD T-score, 4 of these subjects were osteoporotic, 13 were osteopenic, Volume 9, 2006
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Fig. 1. Phase 1: Effect of calcium tablets on phantom bone mineral density (BMD). Each bar is the mean (SEM) of 3 measurements (3 with no supplements, 3 overlying tissues, and 3 over bones). GE Healthcare Lunar and Hologic encapsulated phantoms were used. Measured L1–L4 BMD was often increased when supplements were placed over bone on either phantom. Although changes exceeded the least significant change (LSC) for the individual phantoms (0.011 and 0.019 grams/cm2), none were greater than the clinical LSC of 0.028 g/cm2. Data are mean 6 standard error of the mean. *Different than no supplement; p 0.01. Note: solid grey line indicates mean BMD; dashed grey line indicates LSC. and 19 had normal spine BMD. No differences between calcium supplement groups were present with the exception that the L1–L4 BMD T-score was lower ( p ! 0.05) in the Citracal (21.6) than in the People’s Choice (20.1) group. Mean (standard deviation [SD]) L1–L4 BMD for the Citracal, People’s Choice, and Oscal groups was 0.989 g/cm2 (SD: 0.112 g/cm2), 1.177 g/cm2 (SD: 0.249 g/cm2), and 1.053 g/cm2 (SD: 0.110 g/cm2), respectively.
Calcium Tablet Visualization Calcium tablets were visually identifiable in 33% of postsupplement DXA scans (Fig. 2A). Calcium citrate (Citracal) was not visualized in any scan image. However, calcium carbonate was visualized for both OsCal and People’s Choice supplements. When visualized, 46% appeared as tablets, 37.5% as tissue variation, and 16.5% as overlaid bone (Fig. 2B–2D). In 3 of 4 instances when a tablet was visualized to overlay bone, the BMD did not differ by greater than the LSC. In a single instance, the L1–L4 BMD was increased by 0.037 g/cm2. It should be noted that the calcium supplements could have been unappreciated by the technologist and clinician without a prior image for comparison; examples Journal of Clinical Densitometry
Fig. 2. Calcium tablet visualization. The citrate was never visualized, whereas the carbonates were seen about half of the time (A). In addition, there was variation in ease of identifying tablets on the images. Some were very evident (B), on some other images it was difficult to differentiate between tablets and slight soft tissue variation occasionally observed on DXA images (C), whereas some overlay bone as illustrated (D). In many instances in which such subtle differences were present it was difficult to see tablets without a comparison scan. are shown in Figs 2B–2D. When a tablet was in an area identified as soft tissue (n 5 20), the software appropriately neutralized it (identifying the tablet as ‘‘neutral,’’ not as artifact, soft tissue, or bone) 85% of the time. Volume 9, 2006
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Krueger et al. Effect of Calcium Tablet Ingestion on L1–L4 BMD (Figure 3A–3C) Bone density differences were observed in all groups. The mean delta for Citracal was 0.017 g/cm2 6 0.01, with 4 subjects exceeding the LSC of 0.028 g/cm2 at 5 time points. Similar results were obtained with OsCal for which the mean delta BMD was also 0.017 g/cm2 6 0.02, with values outside the LSC in 4 subjects at 5 time points. Finally, with People’s Choice, the mean delta BMD was 0.023 g/cm2 6 0.02 and 5 subjects demonstrated subsequent scan values outside the LSC at 7 time points. Subject age, BMD, and tablet visualization were not predictive of changes greater than the LSC; surprisingly, of the 4 times tablets were visualized over bone, the L1–L4 BMD fell outside the LSC only once (data not shown). The previously noted BMD changes led to changes in T-score, which resulted in alteration of diagnostic classification applying the WHO criteria in 11% of subjects (4 of 36: 1 each in the Citracal and People’s Choice and 2 in the OsCal group).
Phase 3: Precision Assessment Followed by Calcium Ingestion Fifteen postmenopausal women (mean age: 64 yr; range: 53.2–79.4 yr) were enrolled; their mean BMI was 28 kg/m2 (range: 19.4–39.9 kg/m2), and their L1–L4 T-score was and 20.40 (23.7 to 1.4). Calcium tablets were visualized in 43% of postsupplement scans (Fig. 2A); 6 tablets overlaid bone with only 1 resulting in a BMD change outside the LSC. Differences in BMD outside the established LSC of 0.028 g/cm2 were observed in 20% of scans obtained after calcium intake (Fig. 4). The mean BMD delta of the first two precision scans compared with the third was only 0.012 g/cm2 6 0.01, and one subject’s BMD delta fell outside the LSC at a single time point. In contrast, the mean delta BMD postsupplement was greater ( p ! 0.01) than prior to supplement intake 0.020 g/cm2 6 0.01; with 5 subjects falling outside the LSC at 6 time points (Fig. 4). The change in BMD following People’s Choice ingestion resulted in a diagnostic change when applying the WHO criteria in 7% (1 of 15) of these subjects.
Discussion
Fig. 3. Phase 2: Effect of calcium supplement ingestion (A, B, C) on individual bone mineral density (BMD). After calcium supplement ingestion, the L1–L4 BMD change exceeded our least significant change (LSC) in 13 of 36 subjects at 17 individual times. All supplements had an effect, despite substantial differences in the frequency with which they were visualized on the scan. Asterisks note when a tablet was visualized on the scan.
Journal of Clinical Densitometry
Many DXA centers recommend that patients avoid calcium supplement ingestion for 24 hours prior to DXA scanning (14). However, data evaluating a potential effect of calcium tablets on BMD measurement are quite limited (15,17,18). This study suggests that both ex vivo phantom BMD and in vivo human L1–L4 BMD measurements may be affected by the presence of calcium supplements. Substantial differences in tablet visualization on the DXA images were present between the citrate and carbonate supplements tested. Despite this, there was no relationship between tablet visualization and change in L1–L4 BMD suggesting the supplement may affect BMD even when it has dissolved enough such that it is not visible. In addition, although the software appropriately neutralized visible tablets most of the time, measured BMD was often impacted by greater than Volume 9, 2006
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163 measurement whether they overlaid bone or soft tissue. This was subsequently confirmed in vivo. In summary, some types of calcium supplements, when ingested 15 or 30 minutes before spine DXA scanning, are often visualized on the DXA image. Whether the supplements are visualized or not, L1–L4 BMD may be altered by an amount greater than the clinical LSC. There is no apparent trend of calcium supplements to increase or decrease the measured BMD. Patient age or BMD does not seem to alter the impact of calcium supplements on BMD. As such, calcium supplements should not be ingested 30 minutes prior to spine DXA scan performance.
References
Fig. 4. Phase 3: Precision assessment followed by calcium intake. A greater scatter of bone mineral density (BMD) values ( p ! 0.01) is apparent after calcium ingestion. Moreover, BMD change exceeded the LSC (0.028 grams/cm2) in 5 subjects at 6 time points. Whether or not a tablet was visualized did not predict whether a BMD change greater than the least significant change (LSC) would occur. Asterisks note when a tablet was visualized on the scan.
the calculated least significant change derived from these subjects. As such, tablet visualization (or nonvisualization) does not allow the interpreting physician to determine if the BMD result may have been altered by calcium supplement ingestion. Moreover, even when tablets are visualized to overlay bone, the L1–L4 BMD does not increase by an amount greater than the LSC. As it does not seem to be possible to recognize that calcium tablets are confounding the study at the time of analysis, it is reasonable that these artifacts be avoided by asking patients to refrain from their ingestion prior to DXA scan performance. The calcium supplements selected for this study reflect those widely used in our clinical practice. It is possible that different results may be obtained with other products or calcium preparations (e.g., calcium phosphate). Moreover, it is not clear that similar results would be obtained if a longer time was allowed to elapse between calcium supplement intake and DXA scan performance. The short time interval was selected for this study as a worse-case scenario and does not allow determination of how long such effects on BMD persist. Whether abstinence from calcium supplements for 24 hours prior to DXA scan performance, as is often currently recommended, is necessary requires further study. In addition, future evaluation of the impact of ingesting other tablets (e.g., iron supplements), and the impact of dietary calcium on BMD measurements seems appropriate. The difference in BMD response to calcium supplement placement on a GE Healthcare Lunar and Hologic spine phantom is interesting and unexpected. Perhaps this reflects the difference in percent of fat detected (Lunar w36% vs Hologic w75%). Nonetheless, the phantom data is useful in that it suggested that calcium supplements may impact BMD Journal of Clinical Densitometry
1. Watts NB. 2004 Fundamentals and pitfalls of bone densitometry using dual-energy x-ray absorptiometry (DXA). Osteoporos Int 15:847–854. 2. Jacobson JA, Jamadar DA, Hayes CW. 2000 Dual x-ray absorptiometry: recognizing image artifacts and pathology. Am J Roentgenol 174:1699–1705. 3. Liu G, Peacock M, Eilam O, Dorulla G, Braunstein E, Johnston CC. 1997 Effect of osteoarthritis in the lumbar spine and hip on bone mineral density and diagnosis of osteoporosis in elderly men and women. Osteoporos Int 7:564–569. 4. Frye MA, Melton LJ, Bryant SC, et al. 1992 Osteoporosis and calcification of the aorta. Bone Miner 19:185–194. 5. Drinka PJ, DeSmet AA, Bauwens SF, Rogot A. 1992 The effect of overlying calcification on lumbar bone densitometry. Calcif Tissue Int 50:507–510. 6. Orwoll ES, Oviatt SK, Mann T. 1990 The impact of osteophytic and vascular calcifications on vertebral mineral density measurements in men. J Clin Endocrinol Metab 70:1202–1207. 7. Hauache OM, Vieira JGH, Alonso G, Martins LRF, Brandao C. 2000 Increased hip bone mineral density in a woman with gluteal silicon implant. J Clin Densitom 3:391–393. 8. Rivera M, Humeres P, Gonzalez P. 1998 Increased bone mineral density in dual x-ray densitometry due to gluteal implants. J Clin Densitom 24(1):51–53. 9. Bonnick SL, Lewis LA. 2002 Bone densitometry for technologists. Humana Press, New Jersey. 84–88. 10. Bohdiewicz PJ, Kahn A. 2002 A dual-energy x-ray absorptiometry artifact and potential pitfall the nonremovable umbilical ring. Clin Nucl Med 27(12):911–912. 11. Binkley N, Krueger D, Vallarta-Ast N. 2003 An overlying fat panniculus affects femur bone mass measurement. J Clin Densitom 6:199–204. 12. Kirac FS, Yuksel D, Yaylali OT. 2001 Pitfalls in the measurement of bone mineral density by the dual-energy x-ray absorptiometric method. Clin Nucl Med 26:874–875. 13. Chan PS, Binkley NC, Lalande BM, Young S, Shaker JL. 2004 Artifactual reduction in bone density as a result of Technetium99m MDP for bone scanning. J Clin Densitom 7:457–458. 14. RadiologyInfo Bone Densitometry. 2005 (10/6/05, http: //www.radiologyinfo.com/content/dexa.htm). 15. Srikureja DP, Speith M, Suarino V. 2004 Density of 1001 pills compared to a phantom transverse process. J Clin Densitom 7:230. 16. Precision assessment and radiation safety white paper. 2005 (10/8/05, http://www.iscd.org/visitors/resources/index.cfm). 17. Robertson S, Kendler D. 2004 Calcium tablet artifact effects on spine DXA. J Clin Densitom 7:223. 18. Kiebzak G, Schmeer P, Van Pelt J. 2004 Insoluble intestinal calcium complexes may affect monitoring but not diagnosis. J Clin Densitom 7:239. Volume 9, 2006
Original Article
Calcium Supplement Ingestion May Alter Lumbar Spine Bone Mineral Density Measurement Diane Krueger,* Mary Checovich, Dessa Gemar, Xiaodan Wei, and Neil Binkley University of Wisconsin Osteoporosis Clinical Center & Research Program, Madison, WI
Abstract Densitometry centers commonly request patients abstain from ingesting calcium supplements prior to dualenergy X-ray absorptiometry (DXA) examination to avoid interference with bone mineral density (BMD) measurement. However, it is not clear that this practice is necessary. This study assessed the impact of recent calcium supplement intake on lumbar spine BMD measurement. The phase 1 experiment demonstrated BMD differences when placing a supplement over various areas of two encapsulated phantoms. To determine whether these results were clinically relevant, the phase 2 study enrolled 36 subjects who received spine scans before and after random assignment to ingest one Citracal, OsCal or People’s Choice tablet providing 315, 500, and 600 mg of elemental calcium, respectively. The phase 3 study evaluated 15 subjects that had three spine scans with repositioning between to establish BMD precision, and then ingested a calcium carbonate tablet. Post-dosing scans were performed 15 and 30 minutes after tablet ingestion. The difference in L1–L4 BMD on subsequent scans was compared with the study derived least significant change (LSC) of 0.028 g/cm2. In phase 2, L1–L4 BMD changes outside the LSC occurred in 36% of subjects with 47% having visualized tablets. Similarly, 33% of the phase 3 subjects demonstrated changes outside the LSC after calcium ingestion and 53% of the subjects in phase 3 had tablets visualized. Visualization of calcium tablets was not associated with BMD changes. In conclusion, calcium tablet intake may affect measured L1–L4 BMD within 30 minutes of ingestion. As such, it is appropriate to request patients abstain from calcium tablet ingestion prior to a spine DXA examination. Key Words: Artifact; bone mineral density; calcium supplements; DXA.
affects DXA measured results (12,13). It is widely assumed that calcium tablet ingestion would have a similar impact, thereby confounding spine DXA results. As calcium tablets may be an avoidable artifact, many DXA centers and the American College of Radiology/Radiological Society of North America routinely advise against their ingestion for 24 hours prior to scan performance (14). Interestingly, these recommendations to avoid calcium tablets prior to DXA scanning do not extend to other medications or supplements and ex vivo data findings presented in abstract form suggest that many tablets may alter phantom BMD measurement (15). As patients and providers frequently question the need to abstain from calcium ingestion, and few studies have evaluated this issue, we investigated the effect of different calcium supplements on DXA-measured spine BMD using phantoms and humans.
Introduction Optimal bone density measurement using DXA demands minimization of artifacts (1). Many of these are internal and can not be removed, such as surgical hardware, osteoarthritis, calcified aortas, or implants (2–8). However many are external, such as metal objects (e.g., zippers) or buttons made of shells (9,10), and are routinely removed. Additionally, fat panniculi, when present, are retracted (11). A third category of temporary internal artifact also exists. Technetium and barium that has not cleared the gastrointestinal tract adversely Received: 10/12/05; Revised: 12/26/05; Accepted: 01/16/06. *Address correspondence to: Diane Krueger, BS, CDT, University of Wisconsin Osteoporosis Research Program, 2870 University Avenue, Suite 100, Madison, WI 53705. E-mail: [email protected]
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Subjects and Methods Phase 1: Calcium Supplements on Phantoms Acrylic encapsulated spine phantoms from GE Healthcare Lunar (Madison, WI) and Hologic (Bedford, MA) were utilized. Each phantom was scanned alone, then subsequently with a single tablet of 5 different calcium supplements overlaying phantom ‘‘soft tissue’’ and again with the supplements overlaying ‘‘bone.’’ The calcium supplements tested in this phase of the study were as follows: Citracal (315 mg; calcium citrate; Mission Pharmacal, St. Louis, MO); OsCal (500 mg; calcium carbonate; GlaxoSmithKline, Moon Township, PA); People’s Choice (600 mg; calcium carbonate; Dollar Tree Stores Inc., Norfolk, VA); Tums Smooth Dissolve (300 mg; calcium carbonate; GlaxoSmithKline, Brentford, UK) and Viactiv (500 mg; calcium carbonate; McNeil-PPC Inc., Fort Washington, PA). The 3 combinations (no calcium present, calcium supplement placed to overlay bone, and calcium supplement placed to overlay soft tissue) were each scanned 3 times. The calcium tablet, but not the phantom, was repositioned between each scan.
Phase 2: Human Calcium Supplement Ingestion Lumbar spine DXA scans were performed on 36 adult volunteers. Subsequently, all participants were randomly assigned to receive one tablet of Citracal, OsCal, or People’s Choice at the doses noted in phase 1. These supplements were chosen from the 5 to represent brand name calcium citrate and carbonate supplements, Citracal and OsCal, respectively, and a low cost supplement that consisted of calcium carbonate. In addition, supplement tablets were chosen over the chewables for better visualization. Lumbar spine scans were repeated 15 and 30 min subsequent to calcium ingestion. In summary, this study phase included 3 groups (n 5 12 in each group who had 3 scans performed; baseline: 15 min and 30 min).
Phase 3: Precision Assessment Followed by Calcium Ingestion A lumbar spine DXA precision assessment was performed following an approach recommended by the International Society for Clinical Densitometry (ISCD) (16). Briefly, 3 lumbar spine scans were performed with repositioning between each scan using 15 adult volunteers. Immediately following the third scan, one 600 mg tablet of People’s Choice calcium was taken, as this was most commonly visualized, and spine scans were repeated 15 and 30 min later. Study phases 2 and 3 were reviewed and approved by the University of Wisconsin Health Sciences Human Subjects Committee. All participants provided written informed consent prior to any study procedure being performed.
Densitometry Data Acquisition and Analysis The DXA scans for all study phases were performed using a single GE Healthcare Lunar Prodigy densitometer (Madison, WI) with software version 6.7 or 9.2. Two ISCDcertified technologists performed all scans in phases 1 and 2, and one technologist performed all scans in phase 3. Initial Journal of Clinical Densitometry
Krueger et al. phase 2 scans were autoanalyzed, only correcting intervertebral marker placement. This approach was taken to observe whether or not tablet related changes in soft tissue density would impact the software’s ability to detect bone edges. Point typing was altered in phase 3 when appropriate as is the case in clinical precision assessments. The copy feature was used for all post baseline scans in all 3 study phases. Two ISCD-certified technologists and one ISCD-certified clinician, without knowledge of BMD change, independently assessed tablet visualization on a printed DXA image. When disagreement regarding tablet visualization occurred, group consensus was reached.
Data/Statistical Analyses Dual-energy X-ray absorptiometry precision, and therefore, LSC was calculated using the ISCD precision calculator downloaded from the website (www.ISCD.org) (16). Phantom precision was determined by calculating phantom values from 60 consecutive phantom acquisition days. Using this approach, the LSC for the GE Healthcare Lunar and Hologic acrylic phantoms was 0.011 and 0.019 grams/cm2, respectively. In our human volunteer sample (phase 3), the L1–L4 BMD LSC was 0.028 grams/cm2. Group demographic data in phase 2 and frequency of tablet visualization in phases 2 and 3 were evaluated by the paired t test. To more clearly depict the impact of calcium supplement ingestion on follow-up BMD measurements, all changes from baseline (both BMD increases and decreases) were changed to positive values and the mean deviation from baseline was reported as ‘‘delta BMD.’’ The BMD variability in phase 3 was evaluated using the equality of variances F test. All analyses were performed using Statview software (Abacus, Cary, NC) or Analyze-It (Leeds, UK).
Results Phase 1: Calcium Supplements on Phantoms A statistically significant increase ( p ! 0.01) in L1–L4 BMD was demonstrated in the majority of cases (70%) when the calcium supplement tablet was placed over bone (Fig. 1). Similarly, a statistically significant difference ( p ! 0.01) in L1–L4 BMD was observed 50% of the time when the tablet was placed over soft tissue. Although significant and often outside the phantom LSC (0.011/0.019 g/cm2), none of these differences exceeded the clinical LSC of 0.028 g/cm2. The soft tissue composition differed between these two phantoms with the GE Lunar phantom being read as containing w36% fat and the Hologic phantom containing w75% fat.
Phase 2: Human Calcium Supplement Ingestion Demographics Thirty-three women and 3 men participated in this study phase. Their mean age was 66 yr (range: 36.4–84.2 yr), their body mass index was 26 kg/m2 (range: 18.1–42.2 kg/m2), their L1–L4 BMD scores were 1.064 g/cm2 (range: 0.619– 1.504 g/cm2), and their L1–L4 T-scores were 20.92 (range: 24.6 to 2.7). Applying the World Health Organization (WHO) classification system to lumbar spine BMD T-score, 4 of these subjects were osteoporotic, 13 were osteopenic, Volume 9, 2006
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Fig. 1. Phase 1: Effect of calcium tablets on phantom bone mineral density (BMD). Each bar is the mean (SEM) of 3 measurements (3 with no supplements, 3 overlying tissues, and 3 over bones). GE Healthcare Lunar and Hologic encapsulated phantoms were used. Measured L1–L4 BMD was often increased when supplements were placed over bone on either phantom. Although changes exceeded the least significant change (LSC) for the individual phantoms (0.011 and 0.019 grams/cm2), none were greater than the clinical LSC of 0.028 g/cm2. Data are mean 6 standard error of the mean. *Different than no supplement; p 0.01. Note: solid grey line indicates mean BMD; dashed grey line indicates LSC. and 19 had normal spine BMD. No differences between calcium supplement groups were present with the exception that the L1–L4 BMD T-score was lower ( p ! 0.05) in the Citracal (21.6) than in the People’s Choice (20.1) group. Mean (standard deviation [SD]) L1–L4 BMD for the Citracal, People’s Choice, and Oscal groups was 0.989 g/cm2 (SD: 0.112 g/cm2), 1.177 g/cm2 (SD: 0.249 g/cm2), and 1.053 g/cm2 (SD: 0.110 g/cm2), respectively.
Calcium Tablet Visualization Calcium tablets were visually identifiable in 33% of postsupplement DXA scans (Fig. 2A). Calcium citrate (Citracal) was not visualized in any scan image. However, calcium carbonate was visualized for both OsCal and People’s Choice supplements. When visualized, 46% appeared as tablets, 37.5% as tissue variation, and 16.5% as overlaid bone (Fig. 2B–2D). In 3 of 4 instances when a tablet was visualized to overlay bone, the BMD did not differ by greater than the LSC. In a single instance, the L1–L4 BMD was increased by 0.037 g/cm2. It should be noted that the calcium supplements could have been unappreciated by the technologist and clinician without a prior image for comparison; examples Journal of Clinical Densitometry
Fig. 2. Calcium tablet visualization. The citrate was never visualized, whereas the carbonates were seen about half of the time (A). In addition, there was variation in ease of identifying tablets on the images. Some were very evident (B), on some other images it was difficult to differentiate between tablets and slight soft tissue variation occasionally observed on DXA images (C), whereas some overlay bone as illustrated (D). In many instances in which such subtle differences were present it was difficult to see tablets without a comparison scan. are shown in Figs 2B–2D. When a tablet was in an area identified as soft tissue (n 5 20), the software appropriately neutralized it (identifying the tablet as ‘‘neutral,’’ not as artifact, soft tissue, or bone) 85% of the time. Volume 9, 2006
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Krueger et al. Effect of Calcium Tablet Ingestion on L1–L4 BMD (Figure 3A–3C) Bone density differences were observed in all groups. The mean delta for Citracal was 0.017 g/cm2 6 0.01, with 4 subjects exceeding the LSC of 0.028 g/cm2 at 5 time points. Similar results were obtained with OsCal for which the mean delta BMD was also 0.017 g/cm2 6 0.02, with values outside the LSC in 4 subjects at 5 time points. Finally, with People’s Choice, the mean delta BMD was 0.023 g/cm2 6 0.02 and 5 subjects demonstrated subsequent scan values outside the LSC at 7 time points. Subject age, BMD, and tablet visualization were not predictive of changes greater than the LSC; surprisingly, of the 4 times tablets were visualized over bone, the L1–L4 BMD fell outside the LSC only once (data not shown). The previously noted BMD changes led to changes in T-score, which resulted in alteration of diagnostic classification applying the WHO criteria in 11% of subjects (4 of 36: 1 each in the Citracal and People’s Choice and 2 in the OsCal group).
Phase 3: Precision Assessment Followed by Calcium Ingestion Fifteen postmenopausal women (mean age: 64 yr; range: 53.2–79.4 yr) were enrolled; their mean BMI was 28 kg/m2 (range: 19.4–39.9 kg/m2), and their L1–L4 T-score was and 20.40 (23.7 to 1.4). Calcium tablets were visualized in 43% of postsupplement scans (Fig. 2A); 6 tablets overlaid bone with only 1 resulting in a BMD change outside the LSC. Differences in BMD outside the established LSC of 0.028 g/cm2 were observed in 20% of scans obtained after calcium intake (Fig. 4). The mean BMD delta of the first two precision scans compared with the third was only 0.012 g/cm2 6 0.01, and one subject’s BMD delta fell outside the LSC at a single time point. In contrast, the mean delta BMD postsupplement was greater ( p ! 0.01) than prior to supplement intake 0.020 g/cm2 6 0.01; with 5 subjects falling outside the LSC at 6 time points (Fig. 4). The change in BMD following People’s Choice ingestion resulted in a diagnostic change when applying the WHO criteria in 7% (1 of 15) of these subjects.
Discussion
Fig. 3. Phase 2: Effect of calcium supplement ingestion (A, B, C) on individual bone mineral density (BMD). After calcium supplement ingestion, the L1–L4 BMD change exceeded our least significant change (LSC) in 13 of 36 subjects at 17 individual times. All supplements had an effect, despite substantial differences in the frequency with which they were visualized on the scan. Asterisks note when a tablet was visualized on the scan.
Journal of Clinical Densitometry
Many DXA centers recommend that patients avoid calcium supplement ingestion for 24 hours prior to DXA scanning (14). However, data evaluating a potential effect of calcium tablets on BMD measurement are quite limited (15,17,18). This study suggests that both ex vivo phantom BMD and in vivo human L1–L4 BMD measurements may be affected by the presence of calcium supplements. Substantial differences in tablet visualization on the DXA images were present between the citrate and carbonate supplements tested. Despite this, there was no relationship between tablet visualization and change in L1–L4 BMD suggesting the supplement may affect BMD even when it has dissolved enough such that it is not visible. In addition, although the software appropriately neutralized visible tablets most of the time, measured BMD was often impacted by greater than Volume 9, 2006
Calcium Supplements and Spine BMD
163 measurement whether they overlaid bone or soft tissue. This was subsequently confirmed in vivo. In summary, some types of calcium supplements, when ingested 15 or 30 minutes before spine DXA scanning, are often visualized on the DXA image. Whether the supplements are visualized or not, L1–L4 BMD may be altered by an amount greater than the clinical LSC. There is no apparent trend of calcium supplements to increase or decrease the measured BMD. Patient age or BMD does not seem to alter the impact of calcium supplements on BMD. As such, calcium supplements should not be ingested 30 minutes prior to spine DXA scan performance.
References
Fig. 4. Phase 3: Precision assessment followed by calcium intake. A greater scatter of bone mineral density (BMD) values ( p ! 0.01) is apparent after calcium ingestion. Moreover, BMD change exceeded the LSC (0.028 grams/cm2) in 5 subjects at 6 time points. Whether or not a tablet was visualized did not predict whether a BMD change greater than the least significant change (LSC) would occur. Asterisks note when a tablet was visualized on the scan.
the calculated least significant change derived from these subjects. As such, tablet visualization (or nonvisualization) does not allow the interpreting physician to determine if the BMD result may have been altered by calcium supplement ingestion. Moreover, even when tablets are visualized to overlay bone, the L1–L4 BMD does not increase by an amount greater than the LSC. As it does not seem to be possible to recognize that calcium tablets are confounding the study at the time of analysis, it is reasonable that these artifacts be avoided by asking patients to refrain from their ingestion prior to DXA scan performance. The calcium supplements selected for this study reflect those widely used in our clinical practice. It is possible that different results may be obtained with other products or calcium preparations (e.g., calcium phosphate). Moreover, it is not clear that similar results would be obtained if a longer time was allowed to elapse between calcium supplement intake and DXA scan performance. The short time interval was selected for this study as a worse-case scenario and does not allow determination of how long such effects on BMD persist. Whether abstinence from calcium supplements for 24 hours prior to DXA scan performance, as is often currently recommended, is necessary requires further study. In addition, future evaluation of the impact of ingesting other tablets (e.g., iron supplements), and the impact of dietary calcium on BMD measurements seems appropriate. The difference in BMD response to calcium supplement placement on a GE Healthcare Lunar and Hologic spine phantom is interesting and unexpected. Perhaps this reflects the difference in percent of fat detected (Lunar w36% vs Hologic w75%). Nonetheless, the phantom data is useful in that it suggested that calcium supplements may impact BMD Journal of Clinical Densitometry
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