In this study, we have shown that the MTI varies greatly by skeletal region, sex, and age. MTI was a concept primarily used in adults where peak bone mass has already been achieved and where the annual rates of loss were considered to be similar over many years. In general, the variation in these pediatric MTI values was mostly driven by the large, age-specific differences in the annualized changes in BMD and BMC. The range of annualized rates of change varied from 0 to 18% per year while precision error never varied more than about a factor of 3 between age groups and regions. When BMD and BMC accretion was at its highest in the early teen years, the MTI values were as short as 3 months. As bone accretion rate decreased in the late teen years, the MTI values increased to values substantially higher than 1 year, sometimes over 10 years, due to the rate of change approaching zero. Hence, in healthy children and younger adolescents (less than15 to 16 years of age) statistically and clinically meaningful changes in BMC and BMD are expected at all skeletal sites. The information presented here may provide valuable information in clinical situations to determine how long to wait before a follow-up DXA scan is acquired. MTI is not useful for older adolescents and young adults around the age of peak bone mass when MTI values exceed 1 year and are thus unreliable due to low annual rate of change.
This is one of the largest precision studies to date in children. We found precision errors varied in a different way than the annualized rates of change. For example, the worst precision error in terms of %CV, albeit still reasonable, was found in the youngest ages while the oldest children had the best precision. The absolute precision error in RSME was similar in all age groups except for the spine and TBLH BMC values. Spine and TBLH had worse precision for the youngest age group for BMC and BMD. We attribute the spine and TBLH age-based differences in precision to known reproducibility challenges to DXA systems. For example, DXA precision is generally worse in low density, small bones due to contrast and edge detection issues. Both of these situations are found in the young children. For the same reasons, the older post-pubertal adolescents had precision error values slightly better than previously reported for adults. The older study participants, with bones close to adult size and at lifetime peak bone density levels, had precision error values of 0.6, 0.6, and 1.2 %CV at the spine, total hip, and femoral neck. For comparison, the precision error in 90 postmenopausal women (full adult size bones but bone density lower than peak) using similar Hologic scanners and analysis software was 1.0, 1.1, , and 2.3 %CV for the same sites (10
For the other sites besides spine and TBLH BMC, the precision was not unique by age group for the absolute RMSE error, only for %CV. In these BMD measures (spine, TBLH, femoral neck, total hip, and 1/3rd radius forearm), the differences in the age-specific mean values caused the %CVs to be unique even though the RMSE values were quite similar. Thus, for these measures, the absolute BMD errors appear not to be driven by issues related to bone size or density, and the overall absolute precision values may be used for LSC calculations (not shown.)
This study confirms the conclusion of Leonard et al. (9
) that DXA scanning is more challenging in younger children than older children. In that study, 32 children had DXA scans of the spine BMD, total hip BMD, and whole body BMD and BMC with a Hologic Discovery A (version 12.3.3). Leonard found worse %CV precision errors for younger group (less than 10 years) versus older group (10-18 years). The %CVs for spine, total hip and whole body BMD were 1.2, 1.6 and 1.0 respectively in the younger children compared to 1.1, 1.2, and 1.2 in our study for the youngest group. For the older children, Leonard found 0.7, 1.0, and 0.9 as compared to our study’s 0.6, 0.7, and 0.6. Thus the precision error values for the Leonard study were similar to our study. However, because Leonard used fewer subjects, significant differences were only seen by age for the spine. In our study, significant differences by age were seen for spine, total body, and total hip. Although the Leonard study speculated about the ability to monitor changes in BMD after 3, 6, and 12 months, our study was able to calculate the MTI based on longitudinal changes observed in the whole BMDCS population.
In a study by Margulies et al. (15
) whole body DXA precision error was measured in 49 children aged 5 to 17 years using a GE Lunar Prodigy (GE Lunar, Madison, WI) with software version 6.6 and 6.7. The whole body BMD %CV was found to be 0.73. This compares to our whole population TBLH BMD %CV of 0.95 on the Hologic systems. Even though the technology for X-ray generation, bone identification, are different between GE and Hologic (16
), the precision was similar for the two studies.
Given these findings, what are the implications for clinical DXA scans in children? The ISCD Official Pediatric Positions on DXA Interpretation and Reporting (17
) stated that “The posterior-anterior (PA) spine and total body less head (TBLH) are the most accurate and reproducible skeletal site.” Here we demonstrate that the spine and TBLH were the most reproducible skeletal sites with the largest annual changes for both BMC and areal BMD measurements. Thus, the MTIs of spine and TBLH were also consistently the shortest. The spine and TBLH had MTIs of 6 months or less for BMD and BMC for both boys and girls less than 14 years old. Femoral neck, total hip, and 1/3rd
distal radius have not been previously recommended in young children due to either significant morphological changes taking place during growth (femur) and thus the lack of consistent regions of interest over time (17
), or the lack of pediatric reference data (radius). However, pediatric reference data for 1/3 radius BMD and total femur have recently been published (4
). Furthermore, in this study, although the MTIs of these sites were consistently longer than that of the spine and total body measures, the MTIs were still reasonable with values around 1 year. Thus, our results support the ISCD position that the spine and TBLH are preferred sites of measure. Nevertheless, reasonable monitoring times and precision errors can still be found with the femoral neck, total femur, and 1/3rd
Which skeletal sites should be used for monitoring bone change in children? Bonnick (8
) outlined in the following four general rules to follow regarding monitoring that were derived primarily with adults in mind: 1. Determine the skeletal sites or bone type considered most affected by the disease or its treatment. 2. Determine the site with the greatest expected change in BMD. 3. Determine the site with the best precision, and 4. Avoid peripheral sites. In adults, the sites that fit these rules in most situations have been the spine and total hip. We studied only healthy children and therefore cannot directly address rule 1. However, the spine and TBLH had both the largest annual changes and best precisions and fit the criterion of rules 2 and 3. Rule 4 may not be applicable to children. When studying pediatric metabolic bone disorders, such as rickets, wrist and knee radiographs are typically acquired since these are the fastest growing areas of the skeleton and, therefore, where a deficiency in mineralization is first likely to be depicted. Although this study does not address specific bone disorders of children, there may be further utility to peripheral measures beyond what this study can demonstrate. It would be reasonable to expect that peripheral skeletal sites would provide unique and valuable information for monitoring bone disease in children. In adults, whole body BMD and BMC are typically not good choices for monitoring because of their low annual change rate. But because of skeletal growth, TBLH in children has very large annual changes.
Our study had the following limitations. First, all of our subjects were scanned on systems made by one DXA manufacturer. It is not possible to generalize these MTI values to scans acquired on systems from other manufacturers without further validation. The primary driver of the MTI was the large differences in the age-related changes. It is reasonable to expect that our results would generalize across different DXA manufacturers. Second, these data were acquired on healthy children. The precision would most likely be worse on children with chronic diseases with lower bone mass and density. More importantly, the annual rates of change were also for healthy children, and these are likely to be affected by disease and/or medications. Third, our study utilized short-term precision estimates from scans acquired on the same day. The long-term precision, where time intervals between scans are several days to months, is affected by both patient positioning, soft-tissue changes around the bone, and machine stability (18
). In a study of 40 postmenopausal women over a 7-year period, Patel (19
) found the long-term precision error values to be similar to previously reported short-term precision error values for Hologic systems, 1.12%, 2.21%, 1.32% for spine, femoral neck, and total hip respectively. These values are similar to our findings and support the use of short-term precision error values when estimating MTI. Lastly, DXA is used on children of all ages including newborns and infants (20
). Our study did not include any participants less than 6 years old. It is likely that the precision errors and MTI values for younger children are less favorable.
We conclude that DXA precision errors and annual rates of change for BMD and BMC in children vary with region of interest, age, and sex. The resulting MTI measures are similar for boys and girls at or below pubertal ages, and provide useful guidelines for scanning intervals. The definition of MTI is not applicable for young adults at ages around the occurrence of peak bone mass. For older adolescents and young adults, some other clinical criteria must be used to determine DXA scanning interval.