Combining areal DXA bone mineral density and vertebrae postero-anterior width improves the prediction of vertebral strength

From a clinical point of view, the prediction of FR is one of the most important issues in bone diseases. Owing to the fact that FR is strongly dependent on the BS, we focused on it instead of the weakly defined FR. In the present study, we proved that there is a strong correlation between BS and volumetric bone mineral density estimated from PA DXA measurements. Two parameters estimating volumetric density from PA DXA were involved, and both of them correlated better to BS, represented by the ultimate stress, than aBMD. It was also confirmed that BMAD described elsewhere [10, 15, 17, 18] is a better predictor of BS than aBMD.

The vBMD_av calculated as the DXA aBMD normalized by the average PA vertebral body width is similar to the parameter described by Kroger et al. [24] and Jergas et al. [13] and used in other works [15, 16]. The vBMD_av correlated well with P_max (r = 0.610). The correlation of vBMD to P_max measured directly by QCT is higher than in case of vBMD_av and is equal to 0.648. On the other hand, vBMD_av is considerably more accurate than aBMD (r = 0.511) in BS variability prediction. All of these findings agree with previously published data [13, 15, 16, 24].

We proposed a modification of aBMD geometrical correction. Instead of the average vertebral body width, we proposed the mid-vertebral body width for DXA aBMD normalization. The parameter achieved in this way (vBMD_min) has stronger correlation to P_max than vBMD_av. The vBMD_min describes BS variability better than vBMD_av probably due to the fact that the former contains the information about the mid-vertebral region, which is cross-sectionally characterized by the narrowest axial area distributing the highest stress, so it is especially susceptible to fractures [19].

Both vBMD_min and vBMD_av correlate positively to BS, which means that the higher values of these parameters translate into higher BS and lower FR.

The aBMD adjusted by the vertebral body size improved the BS prediction and probably also FR prediction. Many authors conclude that aBMD cannot be the single parameter influencing BS, but bone dimensions, shape, structure, and an individual patient’s history should also be considered in the assessment of FR [1, 2, 4‐6, 8, 16, 19, 23, 25]. The idea of taking into consideration geometrical parameters in order to support aBMD acquired in DXA and to improve its diagnostic value has been already examined. The combination of aBMD and other parameters, including geometrical, were considered for different skeletal sites in FR prediction. Yu et al. [26] showed in an in vivo study that femoral aBMD, femoral neck width, and body weight could be combined to explain variability in the risk of hip fractures. Some authors claim that it is not enough to measure only aBMD or bone mineral content (BMC) of the forearm to predict the BS of the distal radius. A clinical assessment of BMC and/or cross-sectional area in the radius would provide improved prediction of an individual risk of radius fracture [27].

There are also some data on the vertebral FR assessment utilizing other parameters in addition to aBMD. Most of them support our conclusions [2, 10, 15, 19, 28], but not all. Cheng et al. [19] showed that a combination of aBMD measured in DXA with vertebral body cross-sectional area considerably increases the ultimate load variability prediction. This is contrary to our findings because we did not observe a statistically significant correlation between considered volumetric estimators to F_max. Even the correlation of vBMD measured in means of QCT was on the significance border (r = 0.500). On the other hand, Cheng et al. also showed that vBMD predicts the vertebral ultimate stress more efficiently than aBMD, which is in agreement with our data.

Ross et al. [28] showed in vivo studies that a combination of large vertebral depth and low bone density increases considerably the vertebrae FR. Their results support our findings. The larger vertebral depth (estimated here by \( \overline{W_{PA}} \)) accompanied by lower aBMD translate into lower vBMD_min and vBMD_av. Both indices correlate positively with the vertebral BS, so lower volumetric densities also mean a lower BS, and a higher FR.

Wren et al. [10] described two aBMD geometrical adjustments aiming at the vBMD and BMC assessment from PA DXA. They defined \( vBMD1= aBMD/\sqrt{A} \) and vBMD2 = aBMD/H (H is the vertebral body height). vBMD1 is in fact the same as BMAD considered here and described by other authors [15, 17, 18]. Wren and his group found high correlations between BMC based on DXA adjusted by geometry and QCT but association between vBMD estimated from QCT and aBMD obtained from DXA was insufficient. Calculation of vBMD1 and vBMD2 only slightly improved the correlation to QCT vBMD. The parameters we describe improve the correlation to BS considerably, but it is difficult to compare these two works as Wren et al. correlated their parameters to vBMD and not to P_max as we did. Both vBMD and P_max roughly describe BS, but they represent different physical values.

Dowthwaite and his group [16] compared a group of ex-gymnastic and non-gymnastic women in means of vertebral geometry and vertebral bone density. They stated that the gymnastic group was characterized by shorter but wider vertebral bodies as well as higher aBMD and BMC in comparison to the non-gymnastic group. The calculated FRAX was smaller for gymnastic group. These results are a little bit confusing for our conclusions because we normalized the aBMD by \( \overline{W_{PA}} \) as the estimator of \( \overline{W_{LAT}} \). We assumed the positive correlation between the last two, so according to our findings, the smaller values of \( \overline{W_{PA}} \) (and \( \overline{W_{LAT}} \)) mean higher BS. According to Dowthwaite, \( \overline{W_{PA}} \) increment increases BS while \( \overline{W_{LAT}} \) increment decreases BS [16].

There is a problem connected to the assumption of a correlation between \( \overline{W_{PA}} \) and \( \overline{W_{LAT}} \). It is well known that the vertebral dimensions change with a patient’s age, e.g., Briot et al. studied and observed the vertebral LAT dimension changes [4]. Older vertebrae seem to be wider than younger, but there is an open question about whether the ratio of LAT and AP widths also changes with a patient’s age. To the best of our knowledge, there are no reports suggesting larger increment in AP vertebral dimensions than in LAT dimensions. We checked \( \overline{W_{PA}} \) and W _PA ^min to \( \overline{W_{LAT}} \) correlations and obtained quite high coefficients, but in order to avoid any doubt, we must conclude that this requires further study. The best possibility would be not \( \overline{W_{LAT}} \) estimation but additional DXA measurement in LAT view [15, 16], allowing direct \( \overline{W_{LAT}} \) measurement. Leonard et al. [15] estimated the vBMD in children pairing the PA and LAT DXA results. They applied LAT and PA vertebral sizes in order to calculate the vertebrae volume and vBMD. They concluded that paired PA and LAT scans may increase sensitivity to real trabecular BMC and density variability.

Dall’Ara et al. [8] recently performed in vitro studies concerning the prediction of vertebral BS by finite elements modeling (FEM). They compared the ability of FEM on this field to vBMD achieved from QCT and aBMD. The PA and LAT aBMD was calculated from high-resolution, three-dimensional images in a way that they would be measured in the real DXA study. They concluded that FEM has the greatest ability to properly predict vertebrae mechanical properties, but their findings concerning vBMD and aBMD are interesting in our study context. Accordingly to the Dall’Ara group [8], aBMD in both PA and LAT views are better associated with F_max than vBMD. There is an opposite relationship when considering P_max, vBMD much better predicts ultimate stress than both aBMDs. Their findings were partially confirmed in our results. The correlations between vBMD (and also three described vBMD estimators) are higher than in case of aBMD if consider P_max. Contrary to Dall’Ara’s results, the vBMD of our samples was the best predictor also for F_max, but aBMD acts better than vBMD_min, vBMD_av, and BMAD. The discrepancy between the results of that study [8] and our results was probably caused by different approaches to vBMD estimation. They used total volumetric bone mineral density, taking into account trabecular as well as cortical bone, while we considered in our studies only the cancellous part. This conclusion is speculative and needs further investigation, but if our results would be confirmed, it would mean that vBMD estimated for trabecular bone only is a better choice than the measurement of both trabecular and cortical densities.

Beside vBMD_min and vBMD_av proposed here, BMAD proposed by other authors [10, 15, 17, 18] was also investigated. aBMD variability is caused not only by the real BMC changes but also by body size variability [17]. That problem is especially important for children and adolescents because during growth, fast BMC changes are accompanied by fast changes in stature [10, 18]. BMAD was introduced as a potential solution for this problem. Our results showed that aBMD corrected by A is better associated to P_max than aBMD alone, but vBMD_min and vBMD_av explain P_max variability more accurate. If we consider the ultimate load prediction, BMAD fails as vBMD_min and vBMD_av failed compared to aBMD and vBMD. Vertebrae fracture is the effect dependent not only on external loads but also on the vertebrae properties such as BMC and dimensions. Therefore, we believe the prediction of P_max variability has a higher importance than F_max variability prediction and such parameters such as BMAD, vBMD_min, and vBMD_av are still worth considering. Our results showed that vBMD_min explains P_max variability much better than BMAD does. This is probably connected to the fact that W _PA ^min (used for vBMD_min assessment) reflects the vertebrae geometry changes in LAT view more accurate than A used for BMAD calculations. It is visible if we compare correlations of \( \overline{W_{LAT}} \) to A (r = 0.673) and to W _PA ^min (r = 0.705).

The main limitation of the present study is the low number of vertebrae studied. More reliable conclusions could be derived from a larger population sample, especially involving wider age ranges. It should also be clearly pointed out that our results were obtained in vitro and conclusions for in vivo BS or FR assessment are rather speculative. The potential clinical application of our conclusions requires additional in vivo studies. Because it is impossible to measure ultimate stress or load in vivo, such investigations should consider the dependencies between proposed indices and FRAX.

In this in vitro study, we confirmed that a combination of aBMD measured in means of DXA with geometrical vertebrae measurement allows for more accurate vertebrae mechanical strength prediction than if only DXA results are analyzed. The aBMD normalized by the vertebrae width correlates better to BS than aBMD alone.

The novel parameter proposed in our study utilizes the mid-vertebral body width for aBMD normalization and performs better in BS prediction than if the average vertebral body width or the PA bone area would be applied.

Applying single DXA scanning one can achieve improved description of vertebral BS comparing to aBMD. Better performance probably would be achieved if both PA and LAT scans could be analyzed.