Trabecular Bone Score (TBS) Predicts Vertebral Fractures in Japanese Women Over 10 Years Independently of Bone Density and Prevalent Vertebral Deformity: The Japanese Population‐Based Osteoporosis (JPOS) Cohort Study

Bone strength is predominantly determined by bone density, but bone microarchitecture also plays an important role. We examined whether trabecular bone score (TBS) predicts the risk of vertebral fractures in a Japanese female cohort. Of 1950 randomly selected women aged 15 to 79 years, we analyzed data from 665 women aged 50 years and older, who completed the baseline study and at least one follow‐up survey over 10 years, and who had no conditions affecting bone metabolism. Each survey included spinal imaging by dual‐energy X‐ray absorptiometry (DXA) for vertebral fracture assessment and spine areal bone mineral density (aBMD) measurement. TBS was obtained from spine DXA scans archived in the baseline study. Incident vertebral fracture was determined when vertebral height was reduced by 20% or more and satisfied McCloskey‐Kanis criteria or Genant's grade 2 fracture at follow‐up. Among eligible women (mean age 64.1 ± 8.1 years), 92 suffered incident vertebral fractures (16.7/10³ person‐years). These women were older with lower aBMD and TBS values relative to those without fractures. The unadjusted odds ratio of vertebral fractures for one standard deviation decrease in TBS was 1.98 (95% confidence interval [CI] 1.56, 2.51) and remained significant (1.64, 95% CI 1.25, 2.15) after adjusting for aBMD. The area under the receiver operating characteristic curve of TBS and aBMD combined was 0.700 for vertebral fracture prediction and was not significantly greater than that of aBMD alone (0.673). However, reclassification improvement measures indicated that TBS and aBMD combined significantly improved risk prediction accuracy compared with aBMD alone. Further inclusion of age and prevalent vertebral deformity in the model improved vertebral fracture prediction, and TBS remained significant in the model. Thus, lower TBS was associated with higher risk of vertebral fracture over 10 years independently of aBMD and clinical risk factors including prevalent vertebral deformity. TBS could effectively improve fracture risk assessment in clinical settings. © 2014 American Society for Bone and Mineral Research.     

Measurement of subregional vertebral bone mineral density in vitro using lateral projection dual-energy X-ray absorptiometry: validation with peripheral quantitative computed tomography

Although a strong relationship exists between areal bone mineral density (aBMD) derived from dual-energy X-ray absorptiometry (DXA) and bone strength, the predictive validity of aBMD for osteoporotic vertebral fractures remains suboptimal. The diagnostic sensitivity of DXA may be improved by assessing aBMD within vertebral subregions, rather than relying on an estimate derived from the total area of the vertebra. The objective of this study was to validate a method of measuring subregional vertebral aBMD in vitro using lateral-projection DXA against subregional volumetric BMD (vBMD) measured with peripheral quantitative computed tomography (pQCT). A mixed set of 49 lumbar and thoracic vertebrae from 25 donors were scanned using lateral-projection DXA and pQCT. aBMD and apparent vBMD were measured in 7 vertebral regions (1 total area and 6 subregions) from the lateral DXA scan. vBMD was calculated in anatomically equivalent regions from pQCT scan data, using a customised software program designed to increase efficiency of the analysis process. Significant differences in densitometric parameters between subregions were observed by DXA and pQCT (P < 0.01). Subregional vBMD derived from pQCT was explained by a significant proportion of the variance in DXA-derived aBMD (R ² = 0.51–0.67, P < 0.05) and apparent vBMD (R ² = 0.64–0.75, P < 0.05). These results confirm the validity of measuring aBMD in vertebral subregions using lateral-projection DXA. The clinical significance should now be explored.     

Added value of trabecular bone score over bone mineral density for identification of vertebral fractures in patients with areal bone mineral density in the non-osteoporotic range

Summary

Detection of patients with vertebral fracture is similar for areal bone mineral density (aBMD) and trabecular bone score (TBS) in patients with non-vertebral fracture. In non-osteoporotic patients, TBS adds information to lumbar spine aBMD and is related to an index of spine deterioration.

Introduction

Vertebral fractures (VFs) are more predictive of future fracture than aBMD. The number and severity of VFs are related to microarchitecture deterioration. TBS has been shown to be related to microarchitecture. The study aimed at evaluating TBS in the prediction of the presence and severity of VFs.

Methods

Patients were selected from a Fracture Liaison Service (FLS): aBMD and vertebral fracture assessment (VFA) were assessed after the fracture, using dual-energy X-ray-absorptiometry (DXA). VFs were classified using Genant's semiquantitative method and severity, using the spinal deformity index (SDI). TBS was obtained after analysis of DXA scans. Performance of TBS and aBMD was assessed using areas under the curves (AUCs).

Results

A total of 362 patients (77.3 % women; mean age 74.3?±?11.7 years) were analysed. Prevalence of VFs was 36.7 %, and 189 patients (52.2 %) were osteoporotic. Performance of TBS was similar to lumbar spine (LS) aBMD and hip aBMD for the identification of patients with VFs. In the population with aBMD in the non-osteoporotic range (n?=?173), AUC of TBS for the discrimination of VFs was higher than the AUC of LS aBMD (0.670 vs 0.541, p?=?0.035) but not of hip aBMD; there was a negative correlation between TBS and SDI (r?=??0.31; p?<?0.0001).

Conclusion

Detection of patients with vertebral fracture is similar for aBMD and TBS in patients with non-vertebral fracture. In patients with aBMD in the non-osteoporotic range, TBS adds information to lumbar spine aBMD alone and is related to an index of spine deterioration.     

The predictive value of trabecular bone score (TBS) on whole lumbar vertebrae mechanics: an ex vivo study

Summary

We investigated the association of trabecular bone score (TBS) with microarchitecture and mechanical behavior of human lumbar vertebrae. We found that TBS reflects vertebral trabecular microarchitecture and is an independent predictor of vertebral mechanics. However, the addition of TBS to areal BMD (aBMD) did not significantly improve prediction of vertebral strength.

Introduction

The trabecular bone score (TBS) is a gray-level measure of texture using a modified experimental variogram which can be extracted from dual-energy X-ray absorptiometry (DXA) images. The current study aimed to confirm whether TBS is associated with trabecular microarchitecture and mechanics of human lumbar vertebrae, and if its combination with BMD improves prediction of fracture risk.

Methods

Lumbar vertebrae (L3) were harvested fresh from 16 donors. The anteroposterior and lateral bone mineral content (BMC) and areal BMD (aBMD) of the vertebral body were measured using DXA; then, the TBS was extracted using TBS iNsight software (Medimaps SA, France). The trabecular bone volume (Tb.BV/tissue volume, TV), trabecular thickness (Tb.Th), degree of anisotropy, and structure model index (SMI) were measured using microcomputed tomography. Quasi-static uniaxial compressive testing was performed on L3 vertebral bodies to assess failure load and stiffness.

Results

The TBS was significantly correlated to Tb.BV/TV and SMI (r?=?0.58 and ?0.62; p?=?0.02, 0.01), but not related to BMC and BMD. TBS was significantly correlated with stiffness (r?=?0.64; p?=?0.007), independently of bone mass. Using stepwise multiple regression models, we failed to demonstrate that the combination of BMD and TBS was better at explaining mechanical behavior than either variable alone. However, the combination TBS, Tb.Th, and BMC did perform better than each parameter alone, explaining 79 % of the variability in stiffness.

Conclusions

In our study, TBS was associated with microarchitecture parameters and with vertebral mechanical behavior, but TBS did not improve prediction of vertebral biomechanical properties in addition to aBMD.     

Subregional DXA-Derived Vertebral Bone Mineral Measures are Stronger Predictors of Failure Load in Specimens with Lower Areal Bone Mineral Density,Compared to Those with Higher Areal Bone Mineral Density

Measurement of areal bone mineral density (aBMD) in intravertebral subregions may increase the diagnostic sensitivity of dual-energy X-ray absorptiometry (DXA)-derived parameters for vertebral fragility. This study investigated whether DXA-derived bone parameters in vertebral subregions were better predictors of vertebral bone strength in specimens with low aBMD, compared to those with higher aBMD. Twenty-five lumbar vertebrae (15 embalmed and 10 fresh-frozen) were scanned with posteroanterior- (PA) and lateral-projection DXA, and then mechanically tested in compression to ultimate failure. Whole-vertebral aBMD and bone mineral content (BMC) were measured from the PA- and lateral-projection scans and within 6 intravertebral subregions. Multivariate regression was used to predict ultimate failure load by BMC, adjusted for vertebral size and specimen fixation status across the whole specimen set, and when subgrouped into specimens with low aBMD and high aBMD. Adjusted BMC explained a substantial proportion of variance in ultimate vertebral load, when measured over the whole vertebral area in lateral projection (adjusted R ² 0.84) and across the six subregions (ROIs 2–7) (adjusted R ² range 0.58–0.78). The association between adjusted BMC, either measured subregionally or across the whole vertebral area, and vertebral failure load, was increased for the subgroup of specimens with identified ‘low aBMD’, compared to those with ‘high aBMD’, particularly in the anterior subregion where the adjusted R ² differed by 0.44. The relative contribution of BMC measured in vertebral subregions to ultimate failure load is greater among specimens with lower aBMD, compared to those with higher aBMD, particularly in the anterior subregion of the vertebral body.     

TBS as a Tool to Differentiate the Impact of Antiresorptives onCortical and Trabecular Bone in Children With OsteogenesisImperfecta

Introduction/Background: Osteogenesis imperfecta is a hereditary connective tissue disorder, resulting in low bone mass and high bone fragility. Dual-energy X-ray absorptiometry (DXA) and in adulthood also the trabecular bone score (TBS) are well established to assess bone health and fracture risk. The purpose of this investigation was to assess the usefulness of TBS in respect to different treatment regimes in children with osteogenesis imperfecta. Changes of areal bone mineral density (aBMD) and TBS using DXA scans of children treated with antiresorptive therapies were evaluated. Methodology: DXA scans (aBMD, TBS) of 8 children with OI were evaluated. The scans were taken during a 1 yr period of treatment with bisphosphonates and during 1 yr pilot trial using denosumab. Changes of aBMD and TBS during both treatment regimens were compared. Results: During bisphosphonate treatment aBMD increased about 6.2%, while TBS increased about 2.1%. The difference between aBMD and TBS before and after bisphosphonate treatment was not significant (p?=?0.25). During denosumab treatment aBMD increased around 25.1%, while TBS increased 6.7%. The change of aBMD was significant (p?=?0.007), as was the difference between aBMD and TBS (p < 0.001). Conclusions: Denosumab had a significant effect on both aBMD and TBS but was significantly more pronounced in aBMD. These results suggest a stronger effect of denosumab on cortical bone and the growth plate in comparison to bisphosphonates. Beside the lack of paediatric reference data and the small sample size, the results suggest TBS to be a useful tool for monitoring skeletal changes during development, growth, and antiresorptive therapy in children with OI.     

Bone Microarchitecture Assessed by Trabecular Bone Score Is Independent of Mobility Level or Height in Pediatric Patients with Cerebral Palsy

Bone strength and fracture risk do not only depend on bone density, but also on bone structure. The trabecular bone score (TBS) evaluates homogeneity of bone microarchitecture indirectly by measuring gray-level variations of two-dimensional (2D) DXA images. Although TBS is well-established for adults, there have been only few publications in pediatrics. In this monocentric retrospective analysis, we investigated TBS in children and adolescents with cerebral palsy (CP), a patient group vulnerable to low bone mineral mass due to impaired mobility. The influence of different parameters on TBS and areal BMD (aBMD) were evaluated, as well as the relationship between TBS and aBMD. We compared TBS values of our study population to a reference population. A total of 472 lumbar spine–dual-energy X-ray absorptiometry (LS-DXA) scans of children and adolescents with CP (205 female), aged between 4 and 18 years, were analyzed. The DXA-scans were part of the routine examination. The children had no records of fractures or specific bone diseases. Our study population with CP had similar TBS as the reference population. TBS did not increase with age until an inflection point at 10 years in females, and 12 years in males. Girls had significantly higher TBS than boys (p = .049) and pubertal girls aged 8 to 13 years had significantly higher TBS than prepubertal girls (p = .009). TBS standard deviation score for age (SDS-TBS) and aBMD Z-scores correlated weakly (p < .001; R = 0.276 [males], R = 0.284 [females]). Other than for aBMD Z-scores, SDS-TBS was not influenced by age-adjusted height Z-scores and there was no significant difference in SDS-TBS when grouped by mobility levels, using the Gross Motor Function Classification System (GMFCS). Our results indicate that children with CP have a similar homogeneous distribution of trabecular microarchitecture as controls. Puberty initiation appears to be essential for increase of TBS with age and for sex differences. TBS seems less influenced by body composition, height, and mobility than aBMD. © 2020 The Authors. Journal of Bone and Mineral Research published by American Society for Bone and Mineral Research.     

Trabecular Bone Score Reference Values for Children and Adolescents According to Age,Sex, and Ancestry

Trabecular bone score (TBS) is used for fracture prediction in adults, but its utility in children is limited by absence of appropriate reference values. We aimed to develop reference ranges for TBS by age, sex, and population ancestry for youth ages 5 to 20 years. We also investigated the association between height, body mass index (BMI), and TBS, agreement between TBS and lumbar spine areal bone mineral density (aBMD) and bone mineral apparent density (BMAD) Z-scores, tracking of TBS Z-scores over time, and precision of TBS measurements. We performed secondary analysis of spine dual-energy X-ray absorptiometry (DXA) scans from the Bone Mineral Density in Childhood Study (BMDCS), a mixed longitudinal cohort of healthy children (n = 2014) evaluated at five US centers. TBS was derived using a dedicated TBS algorithm accounting for tissue thickness rather than BMI. TBS increased only during ages corresponding to pubertal development with an earlier increase in females than males. There were no differences in TBS between African Americans and non-African Americans. We provide sex-specific TBS reference ranges and LMS values for calculation of TBS Z-scores by age and means and SD for calculation of Z-scores by pubertal stage. TBS Z-scores were positively associated with height Z-scores at some ages. TBS Z-scores explained only 27% and 17% of the variance of spine aBMD and BMAD Z-scores. Tracking of TBS Z-scores over 6 years was lower (r = 0.47) than for aBMD or BMAD Z-scores (r = 0.74 to 0.79), and precision error of TBS (2.87%) was greater than for aBMD (0.85%) and BMAD (1.22%). In sum, TBS Z-scores provide information distinct from spine aBMD and BMAD Z-scores. Our robust reference ranges for TBS in a well-characterized pediatric cohort and precision error estimates provide essential tools for clinical assessment using TBS and determination of its value in predicting bone fragility in childhood and adolescence. © 2022 American Society for Bone and Mineral Research (ASBMR).     

Bone microarchitecture assessed by TBS predicts osteoporotic fractures independent of bone density: the Manitoba study

The measurement of BMD by dual‐energy X‐ray absorptiometry (DXA) is the “gold standard” for diagnosing osteoporosis but does not directly reflect deterioration in bone microarchitecture. The trabecular bone score (TBS), a novel gray‐level texture measurement that can be extracted from DXA images, correlates with 3D parameters of bone microarchitecture. Our aim was to evaluate the ability of lumbar spine TBS to predict future clinical osteoporotic fractures. A total of 29,407 women 50 years of age or older at the time of baseline hip and spine DXA were identified from a database containing all clinical results for the Province of Manitoba, Canada. Health service records were assessed for the incidence of nontraumatic osteoporotic fracture codes subsequent to BMD testing (mean follow‐up 4.7 years). Lumbar spine TBS was derived for each spine DXA examination blinded to clinical parameters and outcomes. Osteoporotic fractures were identified in 1668 (5.7%) women, including 439 (1.5%) spine and 293 (1.0%) hip fractures. Significantly lower spine TBS and BMD were identified in women with major osteoporotic, spine, and hip fractures (all p < 0.0001). Spine TBS and BMD predicted fractures equally well, and the combination was superior to either measurement alone (p < 0.001). Spine TBS predicts osteoporotic fractures and provides information that is independent of spine and hip BMD. Combining the TBS trabecular texture index with BMD incrementally improves fracture prediction in postmenopausal women. © 2011 American Society for Bone and Mineral Research     

Sequential Therapy With Recombinant Human IGF-1 Followed by Risedronate Increases Spine Bone Mineral Density in Women With Anorexia Nervosa: A Randomized,Placebo-Controlled Trial

Anorexia nervosa is complicated by low bone mineral density (BMD) and increased fracture risk associated with low bone formation and high bone resorption. The lumbar spine is most severely affected. Low bone formation is associated with relative insulin-like growth factor 1 (IGF-1) deficiency. Our objective was to determine whether bone anabolic therapy with recombinant human (rh) IGF-1 used off-label followed by antiresorptive therapy with risedronate would increase BMD more than risedronate or placebo in women with anorexia nervosa. We conducted a 12-month, randomized, placebo-controlled study of 90 ambulatory women with anorexia nervosa and low areal BMD (aBMD). Participants were randomized to three groups: 6 months of rhIGF-1 followed by 6 months of risedronate (“rhIGF-1/Risedronate”) (n = 33), 12 months of risedronate (“Risedronate”) (n = 33), or double placebo (“Placebo”) (n = 16). Outcome measures were lumbar spine (1° endpoint: postero-anterior [PA] spine), hip, and radius aBMD by dual-energy X-ray absorptiometry (DXA), and vertebral, tibial, and radial volumetric BMD (vBMD) and estimated strength by high-resolution peripheral quantitative computed tomography (HR-pCT) (for extremity measurements) and multi-detector computed tomography (for vertebral measurements). At baseline, mean age, body mass index (BMI), aBMD, and vBMD were similar among groups. At 12 months, mean PA lumbar spine aBMD was higher in the rhIGF-1/Risedronate (p = 0.03) group and trended toward being higher in the Risedronate group than Placebo. Mean lateral lumbar spine aBMD was higher, in the rhIGF-1/Risedronate than the Risedronate or Placebo groups (p < 0.05). Vertebral vBMD was higher, and estimated strength trended toward being higher, in the rhIGF-1/Risedronate than Placebo group (p < 0.05). Neither hip or radial aBMD or vBMD, nor radial or tibial estimated strength, differed among groups. rhIGF-1 was well tolerated. Therefore, sequential therapy with rhIGF-1 followed by risedronate increased lateral lumbar spine aBMD more than risedronate or placebo. Strategies that are anabolic and antiresorptive to bone may be effective at increasing BMD in women with anorexia nervosa. © 2021 American Society for Bone and Mineral Research (ASBMR).     

Association of Trabecular Bone Score (TBS) With Incident Clinical and Radiographic Vertebral Fractures Adjusted for Lumbar Spine BMD in Older Men: A Prospective Cohort Study

The association of trabecular bone score (TBS) with incident clinical and radiographic vertebral fractures in older men is uncertain. TBS was estimated from baseline spine dual‐energy X‐ray absorptiometry (DXA) scans for 5831 older men (mean age 73.7 years) enrolled in the Osteoporotic Fractures in Men (MrOS) study. Cox proportional hazard models were used to determine the association of TBS (per 1 SD decrease) with incident clinical vertebral fractures. Logistic regression was used to determine the association between TBS (per 1 SD decrease) and incident radiographic vertebral fracture among the subset of 4309 men with baseline and follow‐up lateral spine radiographs (mean 4.6 years later). We also examined whether any associations varied by body mass index (BMI) category. TBS was associated with a 1.41‐fold (95% confidence interval [CI] 1.23 to 1.63) higher aged‐adjusted odds of incident radiographic fracture, and this relationship did not vary by BMI (p value = 0.22 for interaction term). This association was no longer significant with further adjustment for lumbar spine bone mineral density (BMD; odds ratio [OR] = 1.11, 95% CI 0.94 to 1.30). In contrast, the age‐adjusted association of TBS with incident clinical vertebral fracture was stronger in men with lower BMI (≤ median value of 26.8 kg/m²; hazard ratio [HR] = 2.28, 95% CI 1.82 to 2.87) than in men with higher BMI (> median; HR = 1.60, 95% CI 1.31 to 1.94; p value = 0.0002 for interaction term). With further adjustment for lumbar spine BMD, the association of TBS with incident clinical vertebral fracture was substantially attenuated in both groups (HR = 1.30 [95% CI 0.99 to 1.72] among men with lower BMI and 1.11 [95% CI 0.87 to 1.41] among men with higher BMI). In conclusion, TBS is not associated with incident clinical or radiographic vertebral fracture after consideration of age and lumbar spine BMD, with the possible exception of incident clinical vertebral fracture among men with lower BMI. © 2017 American Society for Bone and Mineral Research.     

Amalgamated Reference Data for Size‐Adjusted Bone Densitometry Measurements in 3598 Children and Young Adults—the ALPHABET Study

The increasing use of dual‐energy X‐ray absorptiometry (DXA) in children has led to the need for robust reference data for interpretation of scans in daily clinical practice. Such data need to be representative of the population being studied and be “future‐proofed” to software and hardware upgrades. The aim was to combine all available pediatric DXA reference data from seven UK centers to create reference curves adjusted for age, sex, ethnicity, and body size to enable clinical application, using in vivo cross‐calibration and making data back and forward compatible. Seven UK sites collected data on GE Lunar or Hologic Scanners between 1996 and 2012. Males and females aged 4 to 20 years were recruited (n = 3598). The split by ethnic group was white 2887; South Asian 385; black Afro‐Caribbean 286; and mixed heritage 40. Scans of the total body and lumbar spine (L₁ to L₄) were obtained. The European Spine Phantom was used to cross‐calibrate the 7 centers and 11 scanners. Reference curves were produced for L₁ to L₄ bone mineral apparent density (BMAD) and total body less head (TBLH) and L₁ to L₄ areal bone mineral density (aBMD) for GE Lunar Prodigy and iDXA (sex‐ and ethnic‐specific) and for Hologic (sex‐specific). Regression equations for TBLH BMC were produced using stepwise linear regression. Scans of 100 children were randomly selected to test backward and forward compatibility of software versions, up to version 15.0 for GE Lunar and Apex 4.1 for Hologic. For the first time, sex‐ and ethnic‐specific reference curves for lumbar spine BMAD, aBMD, and TBLH aBMD are provided for both GE Lunar and Hologic scanners. These curves will facilitate interpretation of DXA data in children using methods recommended in ISCD guidelines. The databases have been created to allow future updates and analysis when more definitive evidence for the best method of fracture prediction in children is agreed. © 2016 American Society for Bone and Mineral Research.     

Vertebral Size,Bone Density,and Strength in Men and Women Matched for Age and Areal Spine BMD

To explore the possible mechanisms underlying sex‐specific differences in skeletal fragility that may be obscured by two‐dimensional areal bone mineral density (aBMD) measures, we compared quantitative computed tomography (QCT)‐based vertebral bone measures among pairs of men and women from the Framingham Heart Study Multidetector Computed Tomography Study who were matched for age and spine aBMD. Measurements included vertebral body cross‐sectional area (CSA, cm²), trabecular volumetric BMD (Tb.vBMD, g/cm³), integral volumetric BMD (Int.vBMD, g/cm³), estimated vertebral compressive loading and strength (Newtons) at L₃, the factor‐of‐risk (load‐to‐strength ratio), and vertebral fracture prevalence. We identified 981 male‐female pairs (1:1 matching) matched on age (± 1 year) and QCT‐derived aBMD of L₃ (± 1%), with an average age of 51 years (range 34 to 81 years). Matched for aBMD and age, men had 20% larger vertebral CSA, lower Int.vBMD (–8%) and Tb.vBMD (–9%), 10% greater vertebral compressive strength, 24% greater vertebral compressive loading, and 12% greater factor‐of‐risk than women (p < 0.0001 for all), as well as higher prevalence of vertebral fracture. After adjusting for height and weight, the differences in CSA and volumetric bone mineral density (vBMD) between men and women were attenuated but remained significant, whereas compressive strength was no longer different. In conclusion, vertebral size, morphology, and density differ significantly between men and women matched for age and spine aBMD, suggesting that men and women attain the same aBMD by different mechanisms. These results provide novel information regarding sex‐specific differences in mechanisms that underlie vertebral fragility. © 2014 American Society for Bone and Mineral Research.     

Trabecular Bone Score has Poor Association With pQCT Derived Trabecular Bone Density in Indian Children With Type 1 Diabetes and Healthy Controls

Background: In children with type 1 diabetes mellitus (T1DM), low trabecular volumetric bone mineral density (Trab vBMD) has been reported. However, studies using the trabecular bone score (TBS) are scarce. The objective of our study was to assess areal bone mineral density at the lumbar spine (LS aBMD), the TBS and Trab vBMD in children with type 1 diabetes in comparison with healthy controls and to assess the relationship of Trab vBMD with TBS.Methods: A total of 205 children were assessed for their LS bone mineral content (BMC) and LS aBMD by dual energy x-ray absorptiometry (DXA) and Trab vBMD at distal radius by peripheral quantitative computed tomography (pQCT). Machine generated Z-scores for both LS aBMD and Trab vBMD were used. The retrospective DXA LS scans in children with T1DM (n=137, age 13.1 ± 3.2 years) and controls (n = 68, age 13.0 ± 2.7 years) were analysed with a research trial version of TBS iNsight software (Medimaps Group). The established TBS cut-offs were used to categorize TBS.Results: The mean LS BMC, LS aBMD, TBS and Trab vBMDs were lower in children with T1DM. TBS was positively correlated with LS aBMD but not with Trab vBMD in both groups. Distribution of T1DM and control children was similar in the TBS categories. Over a fourth of the T1DM children with low Trab vBMD (below -2 Z score) had normal TBS, while, in children with LS aBMD Z-score > -2 from both groups, >50% had degraded or partially degraded TBS. Degraded TBS was seen in half the control children although none of them had low Trab vBMD.Conclusion: We found poor correlation between TBS and Trab vBMD in paediatric diabetic and healthy population. Our results also suggest establishing paediatric TBS cut offs in improving the classification of children having degraded trabecular bone.     

Contribution of the Vertebral Posterior Elements in Anterior–Posterior DXA Spine Scans in Young Subjects

Because DXA is a projection technique, anterior–posterior (AP) measurements of the spine include the posterior elements and the vertebral body. This may be a disadvantage because the posterior elements likely contribute little to vertebral fracture resistance. This study used QCT to quantify the impact of the posterior elements in DXA AP spine measures. We examined 574 subjects (294 females and 280 males), age 6–25 yr, with DXA and QCT. QCT measures were calculated for the cancellous bone region and for the vertebral body including and excluding the posterior elements. DXA data were analyzed for the entire L₃ vertebra and for a 10‐mm slice corresponding to the QCT scan region. BMC and BMD were determined and compared using Pearson's correlation. The posterior elements accounted for 51.4 ± 4.2% of the total BMC, with a significant difference between males (49.9 ± 4.0%) and females (52.8 ± 3.9%, p < 0.001). This percentage increased with age in younger subjects of both sexes (p < 0.001) but was relatively consistent after age 17 for males and 16 for females (p > 0.10). DXA areal BMD and QCT volumetric BMD correlated strongly for the whole vertebra including the posterior elements (R = 0.83), with BMC measures showing a stronger relationship (R = 0.93). Relationships were weaker when excluding the posterior elements. We conclude that DXA BMC provides a measure of bone that is most consistent with QCT and that the contribution of the posterior elements is consistent in young subjects after sexual maturity.     

Bone density,geometry, microstructure,and stiffness: Relationships between peripheral and central skeletal sites assessed by DXA,HR‐pQCT,and cQCT in premenopausal women

High‐resolution peripheral quantitative computed tomography (HR‐pQCT) is a new in vivo imaging technique for assessing 3D microstructure of cortical and trabecular bone at the distal radius and tibia. No studies have investigated the extent to which measurements of the peripheral skeleton by HR‐pQCT reflect those of the spine and hip, where the most serious fractures occur. To address this research question, we performed dual‐energy X‐ray absorptiometry (DXA), central QCT (cQCT), HR‐pQCT, and image‐based finite‐element analyses on 69 premenopausal women to evaluate relationships among cortical and trabecular bone density, geometry, microstructure, and stiffness of the lumbar spine, proximal femur, distal radius, and distal tibia. Significant correlations were found between the stiffness of the two peripheral sites (r = 0.86), two central sites (r = 0.49), and between the peripheral and central skeletal sites (r = 0.56–0.70). These associations were explained in part by significant correlations in areal bone mineral density (aBMD), volumetric bone mineral density (vBMD), and cross‐sectional area (CSA) between the multiple skeletal sites. For the prediction of proximal femoral stiffness, vBMD (r = 0.75) and stiffness (r = 0.69) of the distal tibia by HR‐pQCT were comparable with direct measurements of the proximal femur: aBMD of the hip by DXA (r = 0.70) and vBMD of the hip by cQCT (r = 0.64). For the prediction of vertebral stiffness, trabecular vBMD (r = 0.58) and stiffness (r = 0.70) of distal radius by HR‐pQCT were comparable with direct measurements of lumbar spine: aBMD by DXA (r = 0.78) and vBMD by cQCT (r = 0.67). Our results suggest that bone density and microstructural and mechanical properties measured by HR‐pQCT of the distal radius and tibia reflect the mechanical competence of the central skeleton. © 2010 American Society for Bone and Mineral Research.     

Creation of an Age-Adjusted,Dual-Energy X-ray Absorptiometry–Derived Trabecular Bone Score Curve for the Lumbar Spine in Non-Hispanic US White Women

The trabecular bone score (TBS, Med-Imaps, Pessac, France) is an index of bone microarchitecture texture extracted from anteroposterior dual-energy X-ray absorptiometry images of the spine. Previous studies have documented the ability of TBS of the spine to differentiate between women with and without fractures among age- and areal bone mineral density (aBMD)-matched controls, as well as to predict future fractures. In this cross-sectional analysis of data collected from 3 geographically dispersed facilities in the United States, we investigated age-related changes in the microarchitecture of lumbar vertebrae as assessed by TBS in a cohort of non-Hispanic US white American women. All subjects were 30 yr of age and older and had an L1–L4aBMDZ-score within ±2 SD of the population mean. Individuals were excluded if they had fractures, were on any osteoporosis treatment, or had any illness that would be expected to impact bone metabolism. All data were extracted from Prodigy dual-energy X-ray absorptiometry devices (GE-Lunar, Madison, WI). Cross-calibrations between the 3 participating centers were performed for TBS and aBMD. aBMD and TBS were evaluated for spine L1–L4 but also for all other possible vertebral combinations. To validate the cohort, a comparison between the aBMD normative data of our cohort and US non-Hispanic white Lunar data provided by the manufacturer was performed. A database of 619 non-Hispanic US white women, ages 30–90 yr, was created. aBMD normative data obtained from this cohort were not statistically different from the non-Hispanic US white Lunar normative data provided by the manufacturer (p = 0.30). This outcome thereby indirectly validates our cohort. TBS values at L1–L4 were weakly inversely correlated with body mass index (r = −0.17) and weight (r = −0.16) and not correlated with height. TBS values for all lumbar vertebral combinations decreased significantly with age. There was a linear decrease of 16.0% (−2.47 T-score) in TBS at L1–L4 between 45 and 90 yr of age (vs. −2.34 for aBMD). Microarchitectural loss rate increased after age 65 by 50% (−0.004 to −0.006). Similar results were obtained for other combinations of lumbar vertebra. TBS, an index of bone microarchitectural texture, decreases with advancing age in non-Hispanic US white women. Little change in TBS is observed between ages 30 and 45. Thereafter, a progressive decrease is observed with advancing age. The changes we observed in these American women are similar to that previously reported for a French population of white women (r² > 0.99). This reference database will facilitate the use of TBS to assess bone microarchitectural deterioration in clinical practice.     

The Prevalence of Vertebral Fractures Is Associated With Reduced Hip Bone Density and Inferior Peripheral Appendicular Volumetric Bone Density and Structure in Older Women

Vertebral fractures (VFs) are among the most severe and prevalent osteoporotic fractures. Their association with bone microstructure have been investigated in several retrospective case‐control studies with spine radiography for diagnosis of VF. The aim of this population‐based cross‐sectional study of 1027 women aged 75 to 80 years was to investigate if prevalent VF, identified by vertebral fracture assessment (VFA) by dual‐energy X‐ray absorptiometry (DXA), was associated with appendicular volumetric bone density, structure, and bone material strength index (BMSi), independently of hip areal bone mineral density (aBMD). aBMD was measured using DXA (Discovery; Hologic); BMSi with microindentation (Osteoprobe); and bone geometry, volumetric BMD, and microstructure with high‐resolution peripheral quantitative computed tomography (HRpQCT) (XtremeCT; Scanco Medical AG). aBMD was lower (spine 3.2%, total hip [TH] 3.8%) at all sites in women with VF, but tibia BMSi did not differ significantly compared to women without VF. In multivariable adjusted logistic regression models, radius trabecular bone volume fraction and tibia cortical area (odds ratio [OR] 1.26; 95% confidence interval [CI], [1.06 to 1.49]; and OR 1.27 [95% CI, 1.08 to 1.49], respectively) were associated with VF prevalence, whereas BMSi and cortical porosity were not. The risk of having one, two, or more than two VFs was increased 1.27 (95% CI, 1.04 to 1.54), 1.83 (95% CI, 1.28 to 2.61), and 1.78 (95% CI, 1.03 to 3.09) times, respectively, for each SD decrease in TH aBMD. When including either cortical area, trabecular bone volume fraction or TBS in the model together with TH aBMD and covariates, only TH aBMD remained independently associated with presence of any VF. In conclusion, TH aBMD was consistently associated with prevalent VFA‐verified VF, whereas neither trabecular bone volume fraction, cortical area, cortical porosity, nor BMSi were independently associated with VF in older women. © 2017 American Society for Bone and Mineral Research.     

Bone Impairment in a Large Cohort of Chinese Patients With Tumor-Induced Osteomalacia Assessed by HR-pQCT and TBS

Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome caused by excessive production of fibroblast growth factor 23 (FGF23) by a tumor. Previous studies have revealed generalized mineralization defects and low areal bone mineral density (aBMD) in TIO. However, data on the bone microarchitecture in TIO are limited. In this study, we evaluated the microarchitecture in the peripheral (distal radius and tibia) and axial (lumbar spine) skeleton using high-resolution peripheral quantitative computed tomography (HR-pQCT) and trabecular bone score (TBS) and investigated related factors in a large cohort of Chinese patients with TIO. A total of 186 patients with TIO who had undergone dual-energy X-ray absorptiometry (DXA) or HR-pQCT scans were enrolled. Compared with age-, sex-, and body mass index (BMI)-matched healthy controls, TIO patients (n = 113) had lower volumetric BMD, damaged microstructure, and reduced bone strength in the peripheral skeleton, especially at the tibia. The average TBS obtained from 173 patients was 1.15 ± 0.16. The proportion of patients with abnormal TBS (<1.35) was higher than that with low L₁ to L₄ aBMD Z-score (Z ≤ −2) (43.9% versus 89.6%, p < 0.001). Higher intact fibroblast growth factor 23 (iFGF23), intact parathyroid hormone (iPTH), alkaline phosphatase, and β-isomerized C-terminal telopeptide of type I collagen (β-CTx) levels, more severe mobility impairment, and a history of fracture were associated with poorer HR-pQCT parameters but not with lower TBS. However, greater height loss and longer disease duration were correlated with worse HR-pQCT parameters and TBS. Moreover, TBS was correlated with both trabecular and cortical HR-pQCT parameters in TIO. In conclusion, we revealed impaired bone microarchitecture in the axial and peripheral skeleton in a large cohort of Chinese TIO patients. HR-pQCT parameters and TBS showed promising advantages over aBMD for assessing bone impairment in patients with TIO. A longer follow-up period is needed to observe changes in bone microarchitecture after tumor resection. © 2021 American Society for Bone and Mineral Research (ASBMR).     

The Association Between Trabecular Bone Score and Lumbar Spine Volumetric BMD Is Attenuated Among Older Men With High Body Mass Index

Trabecular bone score (TBS) has been proposed as a dual‐energy X‐ray absorptiometry (DXA) derived measure of underlying quality of trabecular bone; however, TBS is not considered valid for those with body mass index (BMI) >37 kg/m². Our objective was to determine the association between TBS and lumbar spine (trabecular) volumetric BMD (LS‐VBMD) and to examine whether the association varied by BMI and body composition among older men below this clinical threshold. We used regression models to study 3479 men age ≥65 years enrolled in the Osteoporotic Fractures in Men (MrOS) study who had TBS from spine DXA scans, LS‐VBMD from central quantitative computed tomography, measures of trunk fat and lean mass from DXA, and BMI <37 kg/m². TBS was categorized as normal (n = 925), partially degraded (n = 1747), and degraded (n = 807). TBS was inversely related to BMI, trunk fat mass, and trunk lean mass (all p < 0.001). The relationship between TBS and LS‐VBMD was nonlinear with magnitude of effect (slope of regression line using standardized variables) ranging from 0.07 (95% CI, –0.02 to 0.15) among those with degraded TBS up to 0.71 (95% CI, 0.54 to 0.89) among those with normal TBS. The relationship was still nonlinear after adjusting for age, clinical site, and either BMI, trunk lean mass, or trunk fat mass. The magnitude of effect relating TBS and LS‐VBMD also decreased with increasing BMI (interaction, p = 0.090) and increasing trunk lean mass (interaction, p = 0.001), but not with increasing trunk fat mass (interaction, p = 0.224). In summary, the strength of the association between TBS and LS‐VBMD among older men was variable and dependent on BMI and body composition, particularly trunk lean mass. The clinical utility of TBS among older men may be somewhat limited among men with high BMI or high trunk lean mass. © 2016 American Society for Bone and Mineral Research.