Introduction
Vertebral fractures are associated with increased mortality and morbidity and decreased quality of life, and the incidence of these fractures increases with age [
1‐
4]. The prevalence and grade of severity of vertebral fractures have also been shown to be predictive for the risk of new vertebral and non-vertebral fractures, independently of bone mineral density (BMD) measurements [
5‐
7]. However, vertebral fractures remain often underdiagnosed despite their clear value in the assessment of fracture risk [
8,
9]. Conventional spine radiography is traditionally used in the evaluation of vertebral fractures and is considered to be the “gold standard” for detection of these fractures and their grading using the semi-quantitative method of Genant [
10]. Vertebral fracture assessment (VFA) is performed using images obtained by bone densitometers in the same session as bone mineral density measurements are performed to screen for osteoporosis. The VFA technique enables the acquisition of a patient-friendly alternative to conventional radiographs for the assessment of vertebral fractures in a one-stop diagnostic test [
11]. Other advantages of VFA include lower radiation exposure and possibly lower costs. On the basis of available data, VFA has indeed already been incorporated in a number of clinical guidelines replacing conventional radiography for the assessment of prevalent vertebral fractures and thus for the risk of fracture [
12,
13].
However, the advantage of lower-radiation doses used in certain bone densitometry scanners are associated with the drawback of poor image quality and thus of potential poor visualization of the contours of the vertebrae, which could lead to misclassification of fractures or the ascertaining of a vertebra as non-evaluable leading to an inaccurate estimation of fracture risk. A standard protocol or technique for performing VFA has never actually been developed, and the majority of published studies compare the performance of VFA to that of conventional spine radiographs mostly in diverse patient populations, often consisting of small numbers and mostly using different hardware and radiation protocols.
The aims of our study were twofold: first to evaluate the performance of VFA compared to conventional spine radiography in our fracture liaison service (FLS) to assess whether we could replace conventional radiographs by VFA in the diagnosis of vertebral fractures in patients evaluated for osteoporosis after a recent fracture. Second, to systematically review all published literature on the performance of VFA compared to conventional spine radiography in patients evaluated for suspected osteoporosis and to perform a meta-analysis on these data.
Discussion
We performed a systematic review of the literature and a meta-analysis of published data to evaluate the performance of VFA compared to conventional spine radiography in the identification of vertebral fractures in patients at high risk for osteoporosis. Findings from these data show a sensitivity of 0.82 (95% CI, 0.75–0.87) and specificity of 0.99 (95% CI, 0.98–1.00) on a per-vertebra basis and a sensitivity of 0.85 (95% CI, 0.74–0.92) and specificity of 0.93 (95% CI, 0.87–0.97) on a per-person basis. The highly variable sensitivity (47–99%) and specificity (74–100%) between reported studies is likely to be due to the wide age range, variable gender distribution and difference in recruitment of patients (from general practitioners, the outpatient clinics or from an admission ward) between studies. These differences, which were also recognized in a recent systematic review [
32], represent a significant limitation in the interpretation and comparison of findings between studies.
Our meta-analysis of available data from published studies show adequate sensitivity and specificity, also when a vertebral fracture was defined as a vertebral fracture ≥grade 2: sensitivity of 0.81 (95% CI, 0.67–0.91) and specificity of 0.98 (95% CI, 0.94–1.00) for per-vertebra analysis and sensitivity of 0.84 (95% CI, 0.72–0.92) and specificity of 0.90 (95% CI, 0.84–0.94) for per-person analysis. It would be expected that performance of VFA increased if only vertebral fractures ≥grade 2 were included. However, intriguingly, the performance of VFA improved when the analysis included vertebral fractures ≥grade 1 rather than only vertebral fractures ≥grade 2. This may be explained by the fact that two of the largest published studies had excellent performance parameters and provided nearly half of all patients included in the meta-analysis of performance for identifying vertebral fractures ≥grade 1 [
19,
23]. However, an analysis for the detection of vertebral fractures ≥grade 2 was not performed in these two studies, which may explain the difference in sensitivity and specificity in identifying vertebral fractures ≥grade 1 and ≥grade 2. The risk of bias assessment showed that 7 out of 16 studies had a low risk of bias, and 9 were at moderate risk of bias. It is of note, however, that the majority of these studies did not provide adequate information regarding the inclusion process of patients.
Vertebral fracture assessment has become a commonly used tool for the detection of vertebral fractures in the setting of Fracture Liaison Services, clinical care pathways where patients who have recently sustained a fracture are screened for osteoporosis and for potential underlying secondary factors for increased fracture risk. Conventional radiographs of the thoracic and lumbar spine are used as the gold standard for identification of a vertebral fracture. It has been suggested that VFA may represent an attractive alternative to spine radiographs for the detection of vertebral fractures because of the simplicity of the technique (using available DXA device) and lower radiation doses than those used in conventional spine radiographs. However, the advantage granted by a lower radiation dose is unfortunately counterbalanced by higher noise rates and therefore lower image quality, often precluding adequate visualization of vertebrae for the presence of a fracture. This may potentially lead to under diagnosis of vertebral fractures or the need for confirmatory spine radiography.
In our FLS, a VFA is performed in all patients at the time of BMD measurements and conventional spine radiography. We performed a retrospective study comparing low-radiation VFA with conventional spine radiography in the detection of patients with vertebral fractures ≥grade 2 in 542 men and women who had recently sustained a fracture. VFA correctly detected 77% of all patients with a vertebral fracture and correctly identified 80% as having no vertebral fracture. Low-radiation VFA was false positive in 82/410 (20%) patients who had no vertebral fractures on conventional radiography, potentially resulting in over diagnosis and thus initiating unnecessary osteoporosis treatment. Perhaps more worryingly, low-radiation VFA failed to identify a vertebral fracture ≥grade 2 or more in 30 of 132 patients (23%) and more than half of patients had ≥1 vertebrae that could not be evaluated by VFA, the majority of which were at the upper thoracic spine region (level Th4 and Th5), potentially resulting in under diagnosis and under treatment. Of these, only three were missed because the fractured vertebrae were deemed unevaluable by VFA, suggesting poor diagnostic performance, the precise cause of which is as yet to be identified, rather than just poor visualization due to poor image quality.
Our study has strengths as well as limitations. Its main strength is the large group of consecutive patients of both genders all aged ≥50 years who had recently sustained a fracture and who were uniformly evaluated using our FLS standard protocols. A possible limitation of the study is that the inclusion of 144 patients was precluded by the lack of data on VFA or radiography. Whereas a further limitation could be the theoretical influence of a learning curve to obtain VFA images as this tool was only implemented in our FLS care pathway from 2012 onwards, we found no difference in VFA performance in the first 100 patients compared to the last 100 patients (data not shown). A matter of concern in our study is that the number of patients with ≥1 unevaluable vertebrae is rather high, particularly in the upper thoracic region. This problem has been reported in other VFA studies, which led Deleskog and colleagues to suggest that the method was inferior to conventional spinal radiography [
18]. Notwithstanding, it appears that it may be possible to technically enhance the performance of VFA by methods aiming at improving image quality (thus reducing the number of vertebrae that could not be visualized and improving the measurement of height loss of the vertebrae). A limiting factor in the analysis of published data is the general scarcity provided on VFA methodology, particularly radiation dosages, which may have a significant impact on the quality of obtained images. In addition, studies included in our systematic review and meta-analysis were published over a more than 15-year timeframe, spanning the years 2000 to 2016 and the improvement in hardware and software of VFA technology may have potentially influenced the outcomes. The contribution of different technologies to discrepancies in the identification of vertebral fractures has been addressed in a study comparing Lunar Prodigy and Lunar iDXA densitometers, which demonstrated that iDXA had a better performance record for visualization, and thus evaluation, of vertebrae for fractures than the Prodigy densitometer [
33]. So far, there have been no studies comparing VFA performance between single-energy and dual-energy x-ray devices. The discrepancy in results of vertebral fracture assessment using VFA compared to conventional radiology in our study is in contrast to the concordance of results of assessments between radiology and VFA in the majority of studies reported in the systematic review and used in the meta-analysis. This difference could have been influenced by the different methodology used between studies. Quantitative assessment was thus used to evaluate VFA images in our study compared to the use of Genant’s semi-quantitative assessment in the vast majority of studies included in the systematic review and meta-analysis.
In conclusion, from our meta-analysis, findings of published data demonstrate adequate performance parameters of VFA in studies designed for patients at risk for osteoporosis, although a limitation was the very broad range of prevalent vertebral fractures (6.9–100%) and age (23–96 years) which may have influenced study outcomes. The data of our FLS study were in contrast with the numbers of the meta-analysis. The precise cause of the underperformance of VFA in our center is currently being investigated. Our findings suggest that caution should be advocated with the interpretation of VFA data and that centers should check the performance of their VFA device against conventional radiography of the spine before exclusively relying on this tool in the identification of vertebral fractures.
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