Original ArticleNovel Assessment of Subregional Bone Mineral Density Using DXA and pQCT and Subregional Microarchitecture Using Micro-CT in Whole Human Vertebrae: Applications, Methods, and Correspondence Between Technologies
Introduction
The strong relationship between bone mineral density (BMD) and vertebral bone strength underlies the rationale for the use of bone densitometry in assessing and monitoring skeletal integrity and making clinical decisions concerning vertebral fragility (1). Although considered somewhat crude relative to other technologies, dual-energy X-ray absorptiometry (DXA) remains the clinical tool of first choice for this purpose owing to its high precision, accuracy, efficiency, low radiation dose, accessible measurement sites, and low cost relative to other densitometry technologies 2, 3, 4. The strong association between BMD and bone strength (1) explains vertebral BMD as a good predictor of vertebral fracture risk, analogous to blood pressure for stroke, yet BMD cannot be used reliably to determine who will sustain a fracture (5). This creates some uncertainty for clinicians in individual patient care.
Several studies have demonstrated marked differences in the prevalence rate of vertebral fractures among individuals with a comparable BMD as measured by DXA 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18. There are several possible explanations for the poor predictive value of standard DXA parameters when used in isolation, including the influence of clinical risk factors other than areal BMD, inability to measure bone quality, inadequate measurement specificity, and the generally stochastic nature of vertebral fractures (19). Among these, measurement specificity is the only factor that may be improved to optimize the predictive value of DXA, and this remains a focus for our research group.
Both ex vivo and in vivo research has established that the distribution of bone varies throughout the vertebral body 19, 20, yet standard DXA estimation of whole vertebral BMD cannot capture the heterogeneous distribution of intra-vertebral (subregional) BMD. The distribution pattern of bone density is known to influence the bone strength characteristics of the vertebra 21, 22. It follows therefore, that the distribution of intravertebral BMD may be a defining characteristic between individuals with and without osteoporotic vertebral fractures.
We developed a method to measure subregional vertebral BMD using lateral-projection DXA scans, acquired using a Hologic QDR4500A densitometer (23). Our pilot data demonstrate that measurement of areal BMD within vertebral subregions using lateral-projection DXA can better differentiate between individuals with and without osteoporotic vertebral fractures compared with standard AP-projection vertebral DXA parameters (24). Ultimately, a subregional BMD approach could be applied to standard clinical bone densitometry using DXA to potentially provide more reliable and extensive information concerning vertebral fragility. Although compelling, results acquired in the pilot study need replication and verification in a larger clinical study and the DXA protocol requires further validation.
Validation of the subregional BMD approach using DXA can be established against other densitometry modalities, such as peripheral quantitative computed tomography (pQCT) and micro computed tomography (μCT), thereby establishing concurrent validity.
Vertebral bone has trabecular bone structures with thicknesses as small as100 μm (25). Thus, imaging methods with high resolution are essential for their accurate description. The first studies characterizing vertebral microarchitecture with μCT were based on excised bone core samples from which parameters such as bone volume fraction, trabecular thickness, trabecular separation and trabecular number were derived (25). It is now possible to scan the whole vertebral body, rather than an excised core 26, 27, 28, providing data for finite element models (27). Although these studies demonstrate the capacity to examine subregional microarchitecture in the whole vertebral body using μCT, correspondence with subregional analysis of the same vertebral body obtained with clinical instruments, such as DXA, has not yet been examined. In this manuscript we describe the novel approaches used with each modality (DXA, pQCT, and μCT) to derive a vertebral subregional densitometric or micro-architectural value. The aim of this article is to investigate, within the same vertebral bodies, (1) the correspondence in subregional BMD measurements obtained by DXA with those obtained by pQCT, that is, the clinical imaging device for 3D spine measurements in-vivo having higher spatial resolution compared with DXA and (2) with those obtained by μCT, the non-destructive 3D imaging device having the highest resolution.
Section snippets
Study Design
This multi-centre project is currently run through three Australian centres: Curtin University of Technology, Western Australia; SA Pathology, South Australia; and University of Melbourne (Royal Melbourne Hospital), Victoria. Correspondence between subregional measures of vertebral areal BMD, volumetric BMD and microarchitecture are examined using DXA, pQCT, and μCT, respectively, using cadaveric material. Initially, DXA and pQCT scanning are performed in Melbourne, followed by μCT scanning in
Dual Energy X-ray Absorptiometry (DXA)
All scanning was performed using a Hologic (Hologic Inc., Waltham, MA; USA) QDR4500A fan beam densitometer, running operating software version 9.10D. The 12-month precision of the densitometer for the Hologic spine phantom was 0.39% for BMD and 0.58% for BMC. Spines samples were placed supine in a water bath (270 × 180 × 150 mm) of tap water to a depth of 18 cm to simulate soft tissue composition. Specimens were wrapped in water-tight plastic wrap free of air and were secured to the base of the water
DXA Parameters: Areal BMD (mg/cm3), ap.vBMD1 (mg/cm3), ap.vBMD2 (mg/cm3)
DXA-derived data included areal BMD in each subregion (ROI 1–7) and the standard Hologic DXA parameters (total vertebral BMD for the PA and lateral projections, and mid-lateral BMD) for L2. Subregional areal BMD was transformed to apparent volumetric BMD (ap.vBMD) on the assumption that each ROI represented a cylinder. Throughout the remainder of the manuscript, “transformed DXA data” refers to ap.vBMD calculated from areal BMD and subregional geometry. It was not possible to calculate a
Statistical Analysis
Precision of the pQCT method was expressed using a percent coefficient of variation (%CV). A repeated measures ANOVA was performed to evaluate differences in quantitative bone parameters between subregions for each imaging modality, in keeping with earlier work 24, 30. Although there were seven regions of interest, the within subject factor (ROI) was set a priori at k = 4 to ensure that overlapping subregions were not compared post hoc. The first ANOVA model included ROIs 1–4 and the second ANOVA
pQCT Precision
Moderate to high intra-rater precision was observed for the entire pQCT protocol (scan rescan), reflected by a mean (range) %CV of 3.08% (1.02–6.61%) (Table 1). Similarly, moderate to high precision was observed for the Matlab analysis process with a mean (range) %CV of 1.65% (0.34–3.36%) for rater 1, 1.90% (0.56–4.92%) for rater 2, and 3.25% (0.82–9.12%) for inter-rater precision (Table 1).
Subregional Densitometric Characteristics
The mean (SD) areal BMD of the whole L2 vertebrae was 833.625 (144.790) mg/cm2 in the DXA-PA projection
Discussion
We report on the development and application of quantifying subregional bone properties in lumbar vertebrae using DXA, pQCT, and μCT. The data described here support the contention that measurement of subregional vertebral bone properties is feasible using lateral projection DXA by virtue of the correspondence between DXA-derived subregional parameters with pQCT and μCT-derived parameters. Moreover, the patterns of correspondence between DXA and the two criterion modalities (pQCT and μCT) are
Acknowledgments
Funding for these studies was provided by the National Health and Medical Research Council (NHMRC) of Australia, Scoliosis Research Society (USA), and Arthritis Australia. Dr Andrew Briggs is supported by a fellowship awarded by the NHMRC. In kind support was provided by the University of Melbourne Department of Medicine (Royal Melbourne Hospital), and SA Pathology.
References (48)
- et al.
Prediction of thoracic and lumbar vertebral body compressive strength. Correlations with bone mineral density and vertebral region
Bone
(1995) - et al.
Role of dual-energy X-ray absorptiometry in the diagnosis and treatment of osteoporosis
J Clin Densitom
(2007) - et al.
Trabecular architecture in women and men of similar bone mass with and without vertebral fracture: I. Two-dimensional histology
Bone
(2000) - et al.
Discriminative ability of dual energy X-ray absorptiometry site selection in identifying patients with osteoporotic fractures
Bone
(2007) - et al.
In vivo intra-rater and inter-rater precision of measuring apparent bone mineral density in vertebral subregions using supine lateral dual- energy x-ray absorptiometry (DXA)
J Clin Densitom
(2005) - et al.
The osteoporotic vertebral structure is well adapted to the loads of daily life, but not to infrequent “error” loads
Bone
(2004) - et al.
Regional variation in vertebral bone morphology and its contribution to vertebral fracture strength
Bone
(2007) - et al.
Formalin fixation effects on vertebral bone density and failure mechanics. An in-vitro study of human and sheep vertebrae
Clin Biomech
(1994) - et al.
Bone mineral density distribution in thoracic and lumbar vertebrae: an ex vivo study using dual energy X-ray absorptiometry
Bone
(2006) - et al.
Correlation of thoracic and lumbar vertebral failure loads with in situ vs. ex situ dual energy X-ray absorptiometry
J Biomech
(2001)
Precise accurate mineral measurements of excised sheep bones using X-Ray densitometry
Bone Miner
Morphometric analysis of human bone biopsies: A quantitative structural comparison of histological sections and micro-computed tomography
Bone
Quantitative computed tomography estimates of the mechanical properties of human vertebral trabecular bone
J Orthop Res
Vertebral bone density evaluated by DXA and QCT in vitro
Bone
Which bone density measurement?
J Bone Miner Res
European guidance for the diagnosis and management of osteoporosis in postmenopausal women
Osteoporos Int
Meta-analysis of how well measures of bone mineral density predict occurrence of osteoporotic fractures
BMJ
Differential involvement of the dorsal and lumbar spine in osteoporosis
Ann Rheum Dis
Classification of vertebral fractures
J Bone Miner Res
Vertebral deformity in the thoracic spine in post-menopausal women: value of lumbar spine bone density
Brit J Radiol
Which vertebrae should be assessed using lateral dual-energy X-ray absorptiometry of the lumbar spine
Osteoporos Int
Trabecular bone microarchitecture, bone mineral density, and vertebral fractures in male osteoporosis
J Bone Miner Res
The prevalence of vertebral fractures in mild ankylosing spondylitis and their relationship to bone mineral density
Rheumatology
Risk of vertebral fracture and relationship to bone mineral density in steroid-treated rheumatoid arthritis
Ann Rheum Dis
Cited by (23)
Subregional areal bone mineral density (aBMD) is a better predictor of heterogeneity in trabecular microstructure of vertebrae in young and aged women than subregional trabecular bone score (TBS)
2019, BoneCitation Excerpt :This might explain the lack of a significant R2 for the anterior region of the aged group with BV/TV as dependent variable and aBMD as predictor. This effect could be accounted for by scaling the anterior values to a theoretical similar volume [14]. In this study, we refrained from correcting the values since we aimed to investigate if easily applied changes to the ROI could already yield meaningful results.
Impact of bone quality on the performance of integrated fixation cage screws
2018, Spine JournalCitation Excerpt :Furthermore, the heterogeneous nature of the vertebrae cannot be assessed with a single BMD value as local bone quality varies spatially, particularly within trabecular bone because of its complex three-dimensional (3D) microstructure. In fact, a research study confirmed this by performing DEXA measurements on whole vertebra as well as specific regions of vertebra and reported that the BMD of the whole vertebra is significantly different from the BMD within subregions of the vertebra [8]. Cadaver biomechanical studies have also used BMD measurements to classify vertebral bone quality as normal, osteopenic, or osteoporotic.
Peripheral Quantitative Computed Tomography (pQCT) Measures Contribute to the Understanding of Bone Fragility in Older Patients With Low-trauma Fracture
2018, Journal of Clinical DensitometryFunctional Morphology and Medical Imaging
2013, Research Methods in Human Skeletal BiologyFailure strength of human vertebrae: Prediction using bone mineral density measured by DXA and bone volume by micro-CT
2012, BoneCitation Excerpt :In order to then study mechanical properties, the cores were subjected to mechanical testing [22–24]. It is now possible to scan the whole vertebral body, rather than an excised core [25–29]. This provides high-resolution structural data of the whole vertebra in 3D, which can be used in combination with finite element models [26], or with mechanical test data of the whole vertebral body [20,30,31], to examine the resistance to fracture of the vertebra from which vertebral fragility can be inferred.