Regional variation in vertebral bone morphology and its contribution to vertebral fracture strength
Introduction
Osteoporosis is estimated to afflict 200 million women worldwide [1]. In the US alone, osteoporotic fractures are estimated to affect 24 million individuals. 1.5 million new fractures, nearly half of which are vertebral (700,000), are reported each year, outnumbering fractures of the hip and ankle combined [2], [3], [4], [5]. Vertebral fracture may result in pain at the fracture site, loss of height due to vertebral collapse, spinal instability and in many cases a kyphotic deformity [6]. Chronic pain and kyphotic deformity may lead to depression, decreased appetite (leading to poor nutrition), decreased pulmonary function, impaired mobility and a reduction in the quality of life, the ultimate result being a significant increase in morbidity [7], [8], [9], [10]. The World Health Organization defines osteoporosis as a bone mineral density (BMD) of more than 2.5 standard deviations below the mean of a young healthy reference population of the same gender. However, BMD only partially determines fracture risk [11]. Various investigators have found that bone quality, and hence fracture risk, is independent of BMD, as determined through dual energy X-ray absorptiometry (DEXA), and have suggested a role for micro-architecture, turnover, damage accumulation and mineralization [12], [13], [14], [15], [16], [17]. DEXA itself does not account for regional variability in bone quality or vertebral geometry and may include structures that do not add to the mechanical strength of the vertebra, including posterior elements and osteophytes [18]. Furthermore, osteoporosis drug treatment strategies have shown poor correlations between BMD and the risk of vertebral fracture [19], [20], [21], [22], [23], [24]. Hence, vertebral fracture risk may be better defined by more selective methods.
Regional vertebral morphology has been examined using histological methods [11] or using micro-CT measurement of bone cores [25], [26], but few studies consider the analysis of the vertebral body as a whole [27]. Bone volume for vertebrae has been determined to be between 6.5% and 16% [11], [15], [25], [28]. Observed age-related architectural changes to the cancellous bone include: a decrease in bone volume compared with the total vertebra volume (BV/TV), a shift from plate-like trabeculae to more rod-like structures (SMI), a decrease in connectivity density (Conn.D), an increase in orientation of trabeculae along the axis of principle loading (DA), an increase in trabecular separation (Tb.Sp) and a corresponding decrease in trabeculae number (Tb.N) [11], [29], [30], [31]. Trabecular thickness (Tb.Th) has been reported to increase or decrease with age [11], [31]. An increase in trabecular thickness has been explained as either adaptive remodeling of the remaining vertical trabeculae or removal of the thinner struts resulting in an increase in mean trabecular thickness [15], [26], [32]. The etiology of these structural changes remains unclear, whether it is excessive osteoclastic resorption or incomplete osteoblast activity resulting in perforation and thinning of trabecular elements [31], [33], [34]. However, the net result is a reduction in vertebral fracture strength.
The aim of this study was to describe the regional morphology of the elderly human thoracolumbar vertebra using micro-CT and to relate its derived bone architecture parameters (BAP) to vertebral failure. The micro-CT gantry allows for entire functional spine units (FSU) to be scanned non-destructively, allowing subsequent material tests to be performed using physiologically relevant loading configurations. We hypothesize that the bone architecture parameters (BAP) of the less dense anterior and central vertebral body regions will be a better predictor of failure than those of the whole vertebra or DEXA measurements [25], [28]. We extended our regional analysis to determine if BAPs can help explain the reported preferential failure of the superior endplate [35]. Additionally, we considered the role of disc health on endplate thickness, the underlying trabecular bone and vertebral failure.
Section snippets
Sample preparation
The surrounding soft tissue and posterior elements of 22 osteoporotic cadaveric human functional spine units (FSU) were removed (average 74.45 ± 4.25 years). Vertebrae were grouped as follows: one T9–T10, three T11–T12, five T12–L1, five L1–L2, four L2–L3, two L3–L4 and two L4–L5. Previous investigators have found little difference between male and female bone morphology and no major difference in BV/TV between T9 and L5 (1% T9 to L5, 0.5% T11 to L5). Since morphologic changes due to the
Results
Two specimens were removed from the analysis due to an imaging error on one and the presence of extensive vertebral sclerosis on the other. The remaining specimens had an average age of 74.2 ± 4.3 years and were grouped as follows: one T9–T10, three T11–T12, five T12–L1, four L1–L2, four L2–L3, one L3–L4 and two L4–L5. The average BAPs for the sample population (n = 20) are given in Table 2. The mean water content of the nucleus pulposus of the discs was 70 ± 3% and the mean GAG content was 0.17 ± 0.06
Discussion
Vertebrae are not morphologically homogeneous. While vertical homogeneity was observed for the anterior trabecular regions, there is considerable posterior vertical and transverse inhomogeneity, confirming previous reports. The presented methodology differs from previous investigations in that it is not limited to histological analysis of specific regions or the analysis of regional bone plugs, thus allowing non-invasive morphology assessment of the entire vertebral body, followed by mechanical
Acknowledgments
Funding for this research was provided by AOSpine (Grant # SRN 02/105). The authors wish to thank Josh MacNeil for his assistance with micro-CT data acquisition and analysis, Jennifer Vuong for lyophilizing the NP samples and Ladina Ettinger for her assistance with the GAG analysis.
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