Heterogeneity and Spatial Distribution of Intravertebral Trabecular Bone Mineral Density in the Lumbar Spine Is Associated With Prevalent Vertebral Fracture.

The spatial heterogeneity in trabecular bone density within the vertebral centrum is associated with vertebral strength and could explain why volumetric bone mineral density (vBMD) exhibits low sensitivity in identifying fracture risk. This study evaluated whether the heterogeneity and spatial distribution of trabecular vBMD are associated with prevalent vertebral fracture. We examined the volumetric quantitative computed tomography (QCT) scans of the L3 vertebra in 148 participants in the Framingham Heart Study Multidetector CT study. Of these individuals, 37 were identified as cases of prevalent fracture, and 111 were controls, matched on sex and age with three controls per case. vBMD was calculated within 5-mm contiguous cubic regions of the centrum. Two measures of heterogeneity were calculated: (i) interquartile range (IQR); and (ii) quartile coefficient of variation (QCV). Ratios in the spatial distributions of the trabecular vBMD were also calculated: anterior/posterior, central/outer, superior/mid-transverse, and inferior/mid-transverse. Heterogeneity and spatial distributions were compared between cases and controls using Wilcoxon rank sum tests and t tests and tested for association with prevalent fractures with conditional logistic regressions independent of integral vBMD. Prevalent fracture cases had lower mean ± SD integral vBMD (134 ± 38 versus165 ± 42 mg/cm3 , p < .001), higher QCV (0.22 ± 0.13 versus 0.17 ± 0.09, p = .003), and lower anterior/posterior rBMD (0.65 ± 0.13 versus 0.78 ± 0.16, p < .001) than controls. QCV was positively associated with increased odds of prevalent fracture (OR 1.61; 95% CI, 1.04 to 2.49; p = .034), but this association was not independent of integral vBMD (p = .598). Increased anterior/posterior trabecular vBMD ratio was associated with decreased odds of prevalent fracture independent of integral vBMD (OR 0.38; 95% CI, 0.20 to 0.71; p = .003). In conclusion, increased trabecular vBMD in the anterior versus posterior centrum, but not trabecular vBMD heterogeneity, was associated with decreased risk of prevalent fracture independent of integral vBMD. Regional measurements of trabecular vBMD could aid in determining the risk and underlying mechanisms of vertebral fracture. © 2019 American Society for Bone and Mineral Research.

Correspondence between bone mineral density and intervertebral disc degeneration across age and sex.

The distribution of bone tissue within the vertebra can modulate vertebral strength independently of average density and may change with age and disc degeneration. Our results show that the age-associated decrease in bone density is spatially non-uniform and associated with disc health, suggesting a mechanistic interplay between disc and vertebra. PURPOSE: While the decline of bone mineral density (BMD) in the aging spine is well established, the extent to which age influences BMD distribution within the vertebra is less clear. Measures of regional BMD (rBMD) may improve predictions of vertebral strength and suggest how vertebrae might adapt with intervertebral disc degeneration. Thus, we aimed to assess how rBMD values were associated with age, sex, and disc height loss (DHL). METHODS: We measured rBMD in the L3 vertebra of 377 participants from the Framingham Heart Study (41-83 years, 181 M/196 F). Integral (Int.BMD) and trabecular BMD (Tb.BMD) were measured from QCT images. rBMD ratios (anterior/posterior, superior/mid-transverse, inferior/mid-transverse, and central/outer) were calculated from the centrum. A radiologist assigned a DHL severity score to adjacent intervertebral discs (L2-L3 and L3-L4). RESULTS: Int.BMD and Tb.BMD were both associated with age, though the decrease across age was greater in women (Int.BMD, - 2.6 mg/cm3 per year; Tb.BMD, - 2.6 mg/cm3 per year) than men (Int.BMD, - 0.5 mg/cm3 per year; Tb.BMD, - 1.2 mg/cm3 per year). The central/outer (- 0.027/decade) and superior/mid-transverse (- 0.018/decade) rBMD ratios were negatively associated with age, with similar trends in men and women. Higher Int.BMD or Tb.BMD was associated with increased odds of DHL after adjusting for age and sex. Low central/outer ratio and high anterior/poster and superior/mid-transverse ratios were also associated with increased odds of DHL. CONCLUSIONS: Our results indicate that the distribution of bone within the L3 vertebra is different across age, but not between sexes, and is associated with disc degeneration.

Is bone density associated with intervertebral disc pressure in healthy and degenerated discs?

The coupling of the intervertebral disc (IVD) and vertebra as a biomechanical unit suggests that changes in the distribution of pressure within the IVD (intradiscal pressure, IDP) as a result of disc degeneration can influence the distribution of bone density within the vertebra, and vice versa. The goal of this study was to assess the correspondence between IDP and bone density in the adjacent vertebrae, with emphasis on how this correspondence differs between healthy and degenerated IVDs. Bone density of the endplates and subchondral bone in regions adjacent to the anterior and posterior annulus fibrosus (aAF and pAF, respectively) and nucleus pulposus (NP) was measured via quantitative computed tomography (QCT) in 61 spine segments (T7-9, T9-11, T10-12; 71±14years). IDP was measured in the aAF, NP, and pAF regions in 26 of the spine segments (68±16years) while they were tested in flexed (5°) or erect postures. Disc degeneration was assessed by multiple grading schemes. No correlation was found between bone density and IDP in either posture (p>0.104). Regional variations in IDP and, to a greater extent bone density, were found to change with advancing degeneration: both IDP (p=0.045) and bone density (p=0.024) decreased in the NP region relative to the aAF region. The finding of only a modest correspondence between degeneration-associated changes in IDP and bone density may arise from complexity in how IDP relates to mechanical force transmission through the endplate and from limitations of the available IVD grading schemes in estimating the mechanical behavior of the IVD.

Quantitative, 3D Visualization of the Initiation and Progression of Vertebral Fractures Under Compression and Anterior Flexion.

The biomechanical mechanisms leading to vertebral fractures are not well understood. Clinical and laboratory evidence suggests that the vertebral endplate plays a key role in failure of the vertebra as a whole, but how this role differs for different types of vertebral loading is not known. Mechanical testing of human thoracic spine segments, in conjunction with time-lapsed micro-computed tomography, enabled quantitative assessment of deformations occurring throughout the entire vertebral body under axial compression combined with anterior flexion ("combined loading") and under axial compression only ("compression loading"). The resulting deformation maps indicated that endplate deflection was a principal feature of vertebral failure for both loading modes. Specifically, the onset of endplate deflection was temporally coincident with a pronounced drop in the vertebra's ability to support loads. The location of endplate deflection, and also vertebral strength, were associated with the porosity of the endplate and the microstructure of the underlying trabecular bone. However, the location of endplate deflection and the involvement of the cortex differed between the two types of loading. Under the combined loading, deflection initiated, and remained the largest, at the anterior central endplate or the anterior ring apophysis, depending in part on health of the adjacent intervertebral disc. This deflection was accompanied by outward bulging of the anterior cortex. In contrast, the location of endplate deflection was more varied in compression loading. For both loading types, the earliest progression to a mild fracture according to a quantitative morphometric criterion occurred only after much of the failure process had occurred. The outcomes of this work indicate that for two physiological loading modes, the vertebral endplate and underlying trabecular bone are critically involved in vertebral fracture. These outcomes provide a strong biomechanical rationale for clinical methods, such as algorithm-based qualitative (ABQ) assessment, that diagnose vertebral fracture on the basis of endplate depression. © 2015 American Society for Bone and Mineral Research.