Section II: Emerging Uses of Bone DensitometrySpine Trabecular Bone Score Subsequent to Bone Mineral Density Improves Fracture Discrimination in Women
Introduction
Osteoporosis is defined as low bone mass and microarchitectural deterioration of bone tissue, with a consequent increase in bone fragility and susceptibility to fracture. This disease is a major health concern (1), with up to 9 million new osteoporotic fractures annually (2) causing substantial morbidity and mortality worldwide 3, 4. Despite a modest secular decline in fracture rates (5), given population demographics, the number of these fractures is projected to double over the next 40–50 yr (6).
Major efforts to optimally identify those at risk for osteoporosis-related fractures are ongoing. Bone mineral density (BMD), measured by dual-energy X-ray absorptiometry (DXA), has been the gold standard for osteoporosis diagnosis in the absence of prior fragility fracture (7), but approximately half of the fractures occur in people whose BMD T-score is better than −2.5 8, 9. Other factors influencing bone strength and fracture risk include bone turnover, mineralization, macro-geometry, and, importantly, trabecular bone microarchitecture. Thus, additional information about microarchitecture should enhance identification of individuals at risk for fragility fracture.
Trabecular bone score (TBS) is a novel grey-level texture measurement that is based on the use of experimental variograms of 2-dimensional (2D) projection images (10) and is able to differentiate between two 3-dimensional (3D) microarchitectures that exhibit the same bone density but different trabecular characteristics (11). TBS is obtained by analyzing the DXA acquired image that results from a bone density examination; it measures the mean rate of local grey-level variation in these 2D projection images. TBS is therefore not a physical measurement but rather a texture index of trabecular bone, thus, providing information independent of BMD. This is useful as TBS is highly correlated with microarchitecture as measured by micro computed tomography (CT) (12). TBS and BMD combined may enhance fracture risk assessment because they evaluate 2 components of the same bone. Consistent with this, recent work finds TBS to facilitate identification of prevalent fracture. In the Manitoba study, 956 subjects had fractures with normal bone density or osteopenia by the World Health Organization (WHO) classification of spine BMD T-score (13). TBS identified 30% and 43% of these individuals as having high fracture risk from the normal and osteopenic groups, respectively. Conversely, only 7% of the fracture subjects in the osteoporotic group were identified at low fracture risk by TBS. Overall ∼30–40% of the fracture group with normal or osteopenic spine BMD were correctly classified as high risk with TBS. Similar results are found when using the minimum of the hip or spine T-scores for WHO classification instead of the lumbar spine (LS) alone. A similar evaluation of subjects from the Os des Femmes de Lyon (OFELY) population-based study (14), with and without femoral neck fracture, demonstrated TBS, correctly reclassified 25% of fractured subjects at a cost of 13% over-diagnosed control subjects 15, 16. Finally, TBS analysis of the Swiss Evaluation of the Methods of Measurement of Osteoporotic Fracture Risk (SEMOF) study demonstrated that combining BMD T-score ≤−2.5 at any site and high fracture risk by TBS (TBS < 1.200) identified 85% of all women with an osteoporotic fracture (17). In summary, TBS is derived from the texture representation on a DXA image and is related to bone microarchitecture and fracture risk. Specifically, a high TBS reflects strong, fracture-resistant microarchitecture, whereas a low TBS reflects weak, fracture-prone microarchitecture.
Certainly, other methodologies such as high-resolution CT and magnetic resonance imaging are capable of microarchitectural assessment. However, it seems unlikely that these methodologies will see routine clinical use due to a variety of factors including expense, radiation exposure, and availability of appropriate instrumentation. Additionally, with these methodologies, there are no established quantitative cutpoints to discriminate patients into high or low fracture risk groups. In contrast, TBS uses existing DXA images, thus generating no additional radiation exposure and little expense. Moreover, one could anticipate that TBS could use existing data from large studies to establish quantitative values to stratify patients into risk categories.
A limitation of existing TBS studies is lack of spine fracture status. As vertebral fracture is often unappreciated, without spine imaging fracture subjects may be inappropriately grouped with the nonfracture subjects (18). The aim of this study was to evaluate the ability of TBS measurement to discriminate between older women with prior fragility fracture, including unappreciated vertebral fracture, from those without fracture, independent of their BMD. Additionally, we investigate whether the combination of TBS and BMD enhances fracture detection compared with either measurement alone.
Section snippets
Study Subjects
We conducted a retrospective, nonrandom case-control study at the University of Wisconsin Osteoporosis Clinical Research Program (Madison, WI). Postmenopausal Caucasian women, between the ages of 50 and 96 yr, with a body mass index (BMI) between 15 and 37 kg/m² who had DXA-acquired spine bone density scans from prior research study participation were potentially eligible for this evaluation. DXA scans were obtained between 2005 and 2011 on either a Lunar Prodigy or Lunar iDXA densitometer (GE
Study Cohort Description
This study included 429 postmenopausal Caucasian women; 158 (36.8%) were deemed to have an osteoporosis-related fracture either by self-report or on VFA. In this cohort, 91 (21.2%) had vertebral fracture identified on VFA. The fracture and nonfracture groups did not differ in mean age (71.2 vs 72.3 yr; p = 0.16), but women with fractures had a higher BMI (26.2 vs 25.3 kg/m2; p = 0.026; Table 1). In addition, both LS BMD and TBS were less in the fracture group compared with controls, but no
Discussion
In this study, we evaluated the potential diagnostic value of TBS alone, and the combination of TBS and lowest BMD T-score, in differentiating postmenopausal women with, vs those without, prior low trauma fracture including validated vertebral fracture. These results demonstrate that LS TBS discriminates between postmenopausal Caucasian women with fracture and those with no fracture, independent of LS or hip BMD. Additionally, when using a triage approach (TBS subsequent to BMD T-score), a
Acknowledgments
Conflict of interest: TBS iNsight Software is a product of Med-Imaps. Didier Hans is a co-owner of the TBS patent and has corresponding ownership shares.
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