The ISCD recommends spine and whole body as the preferred scan sites for the diagnosis of bone diseases in children [2
]; however, presently no specific recommendations exist for infants. In infants, the head can represent up to 50% of total BMC, and due to inaccuracies in the algorithm for determining skull BMC [17
], the use of the whole body less head measurement may be preferred. As infants grow, it becomes increasingly difficult for them to fall asleep on the DXA bed making the whole body assessment challenging to attain because of movement artefact. The challenge is even greater when you have a child with contractures, mental impairment, or other impediments to scanning which is of importance as these children may have conditions which predispose them to low bone density [18
]. Observations from previous research utilizing pediatric DXA had similar sample size reductions with increasing age [19
]. In one study, movement artefact was reported in 20% of infants scanned rendering the whole body scan unusable [20
]. While our data for whole body BMC is robust up to 6
mo, it is not reliable beyond the 6
mo time point because of our limited sample size due to movement artefact. The data on whole body BMC up to 6
mo was consistent with previous researchers who tracked 87 term infants until 6
]. Due to the variability in obtaining a scan for whole body measurements, regional sites may have more clinical utility. Although data is available for spine measurements using DXA, the previously published data consist mostly of cross-sectional studies. Thus, this present work provides much needed data on healthy infants followed longitudinally in the first year of life.
Lumbar spine vertebra is the easiest measurement site to obtain in infants because it is less subject to movement artefact while providing minimal effective dose of radiation [22
]. Although validation studies for the lumbar spine are not available on the QDR 4500A, precision for lumbar spine measurements in infants has also been reported to be good in an older model with a coefficient of variation of 2.4% and 1.55% for BMC and BMD, respectively [11
]. In addition, spine is formed mainly by trabecular bone, and the rate of bone turnover in the trabecular compartment is much more rapid than in the cortical area, thus, allowing for better tracking of bone changes in clinical trials. Thus, rates of change in bone density will be greater in sites that are predominately trabecular bone such as the spine. The previous literature on lumbar spine bone mineral mass is inconsistent because of the use of different vertebrae for analysis; however, the most recent publications have focused on lumbar vertebrae 1–4 [13
]. While spine BMC is the most easily obtained measurement, it seems to have the lowest rate of accretion over the first year. Even for BMD, increments were only 14% suggesting that growth and mineral accretion is lower during this time compared to the long bones.
Not much is known about infant femur BMC, and this study provides extended knowledge in this area. Cortical bone mass is lower in infants born small-for-gestational-age compared to appropriate-for-gestational-age infants [24
]. Although DXA cannot distinguish between cortical and trabecular bone mass, the content of cortical bone is higher in the femur than in the spine. Interestingly, Weiler et al. [25
] found premature infants born with very low birth weight (≤1200
g) who were supplemented with early minimal enteral feeds had higher elevations in femur bone mass (36%) compared to spine bone mass (16%). In these infants [25
], femur responded to a greater extent than spine and may prove valuable in assessing response to treatment. In addition, Lu et al. [26
] observed that vBMD of the femur and not the lumbar spine was less dependent on growth variables in their study with children and young adults.
The Carter method for the calculation of vBMD has been widely used in adults [27
] and is being increasingly recognized for use with children [30
]. Much of this data has been derived from pencil beam DXA systems [27
], and new fan-beam systems have shown improvements over pencil beam technology [32
]. However, the objective of reporting this calculated value using our dataset was to provide reference data for those clinicians who favor this approach while acknowledging that validation studies have found conflicting results. In cadavers of older adults, vBMD was estimated from an equation similar to the Carter method and was strongly correlated with true vBMD calculated by dividing ash weight by CT-derived volume (r2
= 0.94) [34
]. In children and adolescents, volumetric adjustments improved only slightly the correlation with CT-measured vBMD (r2
= 0.13 and 0.60 from r2
= 0.02 and 0.51 in Tanner stages 1–3 and 4-5, resp.) [35
]. Although this method has been used in infancy [35
], it has not been validated in this population group. It has been suggested that, using an average of anterior posterior (AP), lumbar spine and lateral vertebral scans can approximate vBMD because it makes assessments of vertebral height, width, and depth. Even in infants with osteopetrosis, which causes an increase in bone mass, the average AP and lateral spine measurements correlated well with CT measures of BMD (r2
= 0.851, P
< 0.001) [36
]. In an older group, a comparison of paired AP lateral spine and estimated vBMD using the Carter method found a significant correlation of r
= 0.81 [37
]. Although considered indirectly, this implies that estimated vBMD values show promise even though this remains to be directly validated against CT in infants. In our study, spine vBMD decreases during the first 6
mo because this is a period of rapid bone modeling and the bone is mineralizing at a slower rate than the bone is growing. This is a normal phenomenon as previously observed [38
] and is not a sign of bone loss. The mineralization starts to catch up by 6
mo, and vBMD remains fairly stable up to 12
mo. Volumetric BMD of the spine may become a preferred assessment site because it is also not subject to gender differences in infancy.
Percentile curves for growth have been widely used to assess the nutritional status and general health of infants, children, and adolescents. Bone mass data assessed by DXA is limited in healthy, term infants, and at present there is no available data that presents normative bone mass measurements for infants using percentile charts. The percentile chart that was constructed for spine bone mineral density is displayed to show a possible alternative way to illustrate normative data. Presenting data in this manner will help health care professionals and clinical researchers plot infants and compare to healthy infants of the same age and gender, thus determining adequacy. Larger datasets using prospectively collected data can be utilized in the same manner [14
]. Mode of infant feeding can have an important influence on growth and body composition [39
]. Our data corroborate these findings as we found that being formula fed had a significant effect on the aBMD of the spine by 12
mo of age. The differences in bone mass noted between sexes may be related to differences in growth as anthropometric characteristics were significantly different at each time point; however, there were no growth differences between the feeding groups. According to Statistics Canada's 2003 Canadian Community Health Survey (CCHS) [40
], approximately 85% of Canadian women attempted breastfeeding and 47% did so for longer than 6
mo. In our group, approximately 71% were breast fed for at least 1
mo of age of which 31% were breastfeeding for longer than 6
mo. Therefore, the present data set provides a representative sample of breast-fed and formula-fed infants in keeping with current Canadian statistics. Although a vitamin D supplement was provided to all participating breastfeeding mothers in this study, compliance data was self-reported. An optimal growth reference should be based on a group of healthy, breast-fed infants receiving vitamin D supplementation.
There are limitations with this data because it is not based on a nationally representative sample and observations were recorded at 6
mo intervals during the first year. Infants were recruited solely from Winnipeg, MB, which is located at the 49th parallel north and in south central Canada. Nonetheless, our results were similar to those obtained in southern Ontario [21
]. Furthermore, the prevalence of maternal vitamin D deficiency from this group was similar to that reported from other Canadian studies [41
]. Future research should seek pooled data from cross country sites with observations recorded at 1–3
mo intervals to create a combined bone mass percentile chart data set.
In summary, DXA is a valuable tool for the screening and diagnosis of pediatric bone diseases. This data provides the foundation for future research, but also provides important reference data not currently available, for infants on femur BMC and vBMD. This in addition to clinical data will ultimately aid in the diagnosis, interpretation, and response to treatment for pediatric bone diseases.