Trabecular bone score (TBS) in Cushing's disease: TBS gain after hypercortisolism normalization

It is uncertain whether bone mineral density (BMD) can accurately predict fracture in kidney transplant recipients. Trabecular bone score (TBS) provides information independent of BMD. Kidney transplant recipients had abnormal bone texture as measured by lumbar spine TBS, and a lower TBS was associated with incident fractures in recipients. Trabecular bone score (TBS) is a texture measure derived from dual energy X-ray absorptiometry (DXA) lumbar spine images, providing information independent of bone mineral density. We assessed characteristics associated with TBS and fracture outcomes in kidney transplant recipients. We included 327 kidney transplant recipients from Manitoba, Canada, who received a post-transplant DXA (median 106 days post-transplant). We matched each kidney transplant recipient (mean age 45 years, 39% men) to three controls from the general population (matched on age, sex, and DXA date). Lumbar spine (L1-L4) DXA images were used to derive TBS. Non-traumatic incident fracture (excluding hand, foot, and craniofacial) (n = 31) was assessed during a mean follow-up of 6.6 years. We used multivariable linear regression models to test predictors of TBS, and multivariable Cox proportional hazard regression was used to estimate hazard ratios (HRs) per standard deviation decrease in TBS to express the gradient of risk. Compared to the general population, kidney transplant recipients had a significantly lower lumbar spine TBS (1.365 ± 0.129 versus 1.406 ± 0.125, P < 0.001). Multivariable linear regression revealed that receipt of a kidney transplant was associated with a significantly lower mean TBS compared to controls (-0.0369, 95% confidence interval [95% CI] -0.0537 to -0.0202). TBS was associated with fractures independent of the Fracture Risk Assessment score including BMD (adjusted HR per standard deviation decrease in TBS 1.64, 95% CI 1.15-2.36). Kidney transplant recipients had abnormal bone texture as assessed by TBS and a lower lumbar spine TBS was associated with fractures in recipients.

In the general population, trabecular bone score (TBS) was shown to predict fracture independent of bone mineral density (BMD). In end-stage renal disease patients on hemodialysis (HD), the value of TBS is beyond that of BMD in currently unclear. Our aim was to assess lumbar spine (LS) TBS in HD patients compared with subjects with normal kidney function matched for age, sex, and LS BMD. We assessed TBS and LS and femoral neck (FN) BMD in 98 patient on permanent HD (42.8% males; mean age 57.5 ± 11.3years; dialysis vintage 5.5 ± 3.8years) and 98 control subjects (glomerular filtration rate > 60mL/min) using DXA. We simultaneously controlled for sex, age (± 3years), and LS BMD (± 0.03g/cm2). HD patients had significantly lower LS TBS (0.07 [95% CI 0.03-0.1]; p = 0.0004), TBS T-score (0.83 SD [95% CI 0.42-1.24]; p = 0.0001)) and TBS Z-score (0.81 SD [95% CI 0.41-1.20]; p = 0.0001) than matched controls. TBS significantly correlated with LS BMD in both HD patients (r = 0.382; p = 0.001) and controls (r = 0.36; p = 0.002). The two regression lines had similar slopes (0.3 vs. 0.28; p = 0.84) with different intercepts (0.88 vs. 0.98). TBS adjustment significantly increased the 10-year fracture risk from 3.7 to 5.3 for major osteoporotic fracture and from 0.9 to 1.5 for hip fracture. HD patients have lower TBS than controls matched for LS BMD, indicating altered bone microarchitecture. Also, the magnitude of TBS reduction in HD patients is constant at any LS BMD. Adjustment for TBS partially corrects the absolute 10-year fracture risk.

Trabecular bone score (TBS) as a new complementary approach for osteoporosis evaluation in clinical practice

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).

It is recognized that the trabecular bone score (TBS) provides skeletal information, and frailty measurement is significantly associated with increased risks of adverse health outcomes. Given the suboptimal predictive power in fracture risk assessment tools, we aimed to evaluate the combination of frailty and TBS regarding predictive accuracy for risk of major osteoporotic fracture (MOF). Data from the prospective longitudinal study of CaMos (Canadian Multicentre Osteoporosis Study) were used for this study. TBS values were estimated using lumbar spine (L1 to L4 ) dual-energy X-ray absorptiometry (DXA) images; frailty was evaluated by a frailty index (FI) of deficit accumulation. Outcome was time to first incident MOF during the follow-up. We used the Harrell's C-index to compare the model predictive accuracy. The Akaike information criterion, likelihood ratio test, and net reclassification improvement (NRI) were used to compare model performances between the model combining frailty and TBS (subsequently called "FI + TBS"), FI-alone, and TBS-alone models. We included 2730 participants (mean age 69 years; 70% women) for analyses (mean follow-up 7.5 years). There were 243 (8.90%) MOFs observed during follow-up. Participants with MOF had significantly higher FI (0.24 versus 0.20) and lower TBS (1.231 versus 1.285) than those without MOF. FI and TBS were significantly related with MOF risk in the model adjusted for FRAX with bone mineral density (BMD) and other covariates: hazard ratio (HR) = 1.26 (95% confidence interval [CI] 1.11-1.43) for per-SD increase in FI; HR = 1.38 (95% CI 1.21-1.59) for per-SD decrease in TBS; and these associations showed negligible attenuation (HR = 1.24 for per-SD increase in FI, and 1.35 for per-SD decrease in TBS) when combined in the same model. Although the model FI + TBS was a better fit to the data than FI-alone and TBS-alone, only minimal and nonsignificant enhancement of discrimination and NRI were observed in FI + TBS. To conclude, frailty and TBS are significantly and independently related to MOF risk. Larger studies are warranted to determine whether combining frailty and TBS can yield improved predictive accuracy for MOF risk. © 2020 American Society for Bone and Mineral Research.

Disclosure: M. Kuzma: None. J. Payer: None. P. Vanuga: None. I. Sagova: None. D. Pavai: None. P. Jackuliak: None. Z. Killinger: None. Introduction: Previously, it was thought that increased risk of vertebral fractures (VF) in acromegaly is associated with impaired trabecular bone. More recently, cortical bone was proposed as one of the fracture risk determinant. However, trabecular compartment is still decreased. Glucose intolerance is a frequent complication of acromegaly and is directly attributable to the excess circulating growth hormone and IGF-1 concentrations and thus possibly lead to trabecular bone detoriation.Objectives: To assess effect of glucose metabolism on DXA-derived bone parameters, such as bone mineral density (BMD), trabecular bone score (TBS), cortical and trabecular vBMD, surface BMD and cortical thickness of proximal femur among patients with acromegaly. Patients and methods: In total, 70 consecutive patients (24 males/56 female, mean age = 55.6 years) with acromegaly based on current ADA guidelines were divided in two subgroups according to glucose metabolism(GM): abnormal GM (n=35; 14 males/21 females; 15 with active disease) and normal GM (n=35;10 Males /25 Females; 11 with active disease). Subjects were prospectively followed up for two years. At baseline and year 2; all subjects had pituitary hormonal measures, fasting plasma glucose (FPG), HBA1c, C-peptide, insulin resistance index (IRI) and DXA measurement performed. From DXA, BMD, TBS and 3D-Shaper parameters were derived. Results: At baseline; subjects with abnormal GM had lower TBS (1.166±0.15) in comparison to normal GM subjects (1.232±0.12; p&amp;lt;0.05). Insulin like growth factor 1 (IGF-1), FPG, HBA1c, C-peptide, IRI and bone parameters was correlated in simple regression model. FPG, HBA1c, C-peptide and IRI was negatively associated with TBS. No correlation between GM parameters and other bone measures was observed. Multiple regression model of all GM parameters weighted by IGF-1 revealed HBA1c as a significant predictor of TBS value (Estimate =-0,054; p=0.04). At year 2; FPG and HBA1c was negatively associated with TBS. In multiple regression IGF-1-weighted model, no significant predictor of TBS was observed. Conclusion: Acromegaly subjects with abnormal GM have lower TBS in comparison to those with normal GM. The best GM parameter to predict TBS in acromegaly was HBA1c. This study showed that trabecular bone microstructure, as indirectly assessed by TBS, is likely resulting of impaired glucose metabolism. Presentation: Thursday, June 15, 2023

To compare the trabecular bone score (TBS) between patients with axial spondyloarthritis (axSpA) and matched normal controls and identify risk factors associated with a low TBS. TBS and BMD were assessed in the two groups (axSpA and control) using DXA. Osteoporosis risk factors and inflammatory markers were also assessed. Disease activity and radiographic progression in the sacroiliac joint and spine were evaluated in the axSpA group. Multivariate linear regression analysis was performed to identify risk factors associated with TBS. In the axSpA group, 248 subjects were enrolled; an equal number of age- and sex-matched subjects comprised the control group. The mean TBS was 1.43 (0.08) and 1.38 (0.12) in the control and axSpA groups, respectively (P < 0.001); BMD at the lumbar spine did not differ between the two groups. The TBS was negatively correlated with ESR and CRP levels in the axSpA group only (P < 0.001 and P = 0.007, respectively). Syndesmophytes in the axSpA group was associated with lower TBS (P < 0.001) but higher lumbar BMD (P = 0.021) vs controls. In the multivariate analyses, ESR, CRP and spinal radiographic progression were significantly associated with TBS. TBS assessments revealed poor bone quality in patients with axSpA compared with the matched controls. In axSpA, systemic inflammatory markers were negatively correlated with TBS and spinal radiographic progression and inflammatory markers were independently correlated with low TBS. TBS may, therefore, be a useful clinical tool to identify the risk of osteoporosis in patients with axSpA.

A Comparison of Bone Mineral Density and Its Predictors in HIV-Infected and HIV-Uninfected Older Men

BackgroundVertebral fractures (VFs) are the hallmark of osteoporosis and are more predictive of future fracture than areal Bone Mineral Density (BMD). Number and severity of VFs are related to bone...

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.

Patients with 21-hydroxylase deficiency (21-OHD) are at risk of reduced bone mineral density (BMD) and fracture due to long-term glucocorticoid treatment. Trabecular bone score (TBS) is complementary to conventional BMD as a marker for bone quality in patients with glucocorticoid-induced osteoporosis. The purpose of this study is to evaluate the BMD and TBS in a cohort of patients with 21-OHD and analyse factors related to TBS. An observational study. A total of 46 21-OHD adult patients treated with glucocorticoid for over 10years who visited Peking Union Medical College Hospital between 2015 and 2019 were recruited. Eight male patients included in this study were all under 50years old, and 38 female patients were all premenopausal. Diagnosis was confirmed by multiplex ligation-dependent probe amplification combined with sequencing. Data were collected on physical characteristics, serum hormones and glucocorticoid treatment. Skeletal quality was evaluated by BMD and TBS, and factors related to TBS were analysed. Among the 46 patients, 2 (4.3%) had low BMD (Z-score≤-2), while 11 (23.9%) patients had low TBS (degraded or partially degraded microarchitecture). The proportion of bone abnormality evaluated by TBS was higher than that by BMD (p<.001). Patients with lower TBS had significantly higher daily hydrocortisone dosage (p=.009 for males; p=.019 for females). TBS value was negatively correlated with daily hydrocortisone dosage (r=-.317, p=.026), and positively correlated with BMI in female patients (r=.345, p=.034). And there was a negative correlation between TBS value and the current age in male patients (r=-.741, p=.036). The distribution of genotypes (p=1.000 for male; p=.567 for female) or phenotypes (p=.486 for male; p=.075 for female) had no statistical difference in patients with normal or abnormal TBS. Approximately 24% of patients with 21-OHD had abnormal microarchitecture of their bone in our study, and TBS score was negatively correlated with daily glucocorticoid dosage in patients. TBS may be used alongside conventional BMD as a complementary marker for bone evaluation in 21-OHD patients.

Osteoporotic fractures associated with Cushing's syndrome (CS) may occur despite normal bone mineral density (BMD). Few studies have described alterations in vertebral microarchitecture in glucocorticoid-treated patients and during CS. Trabecular bone score (TBS) estimates trabecular microarchitecture from dual-energy X-ray absorptiometry acquisitions. Our aim was to compare vertebral BMD and TBS in patients with overt CS and mild autonomous cortisol secretion (MACE), and following cure of overt CS. University Hospital. Monocentric retrospective cross-sectional and longitudinal studies of consecutive patients. A total of 110 patients were studied: 53 patients had CS (35, 11 and 7 patients with Cushing's disease, bilateral macronodular adrenal hyperplasia and ectopic ACTH secretion respectively); 39 patients had MACE (10 patients with a late post-operative recurrence of Cushing's disease and 29 patients with adrenal incidentalomas); 18 patients with non-secreting adrenal incidentalomas. 14 patients with overt CS were followed for up to 2years after cure. Vertebral osteoporosis at BMD and degraded microarchitecture at TBS were found in 24% and 43% of patients with CS, respectively (P<.03). As compared to patients with nonsecreting incidentalomas, patients with MACE had significantly decreased TBS (P<.04) but not BMD. Overt fragility fractures tended to be associated with low TBS (P=.07) but not with low BMD. TBS, but not BMD values, decreased with the intensity of hypercortisolism independently of its aetiology (P<.01). Following remission of CS, TBS improved more markedly and rapidly than BMD (10% vs 3%, respectively; P<.02). Trabecular bone score may be a promising, noninvasive, widely available and inexpensive complementary tool for the routine assessment of the impact of CS and MACE on bone in clinical practice.

We found that lumbar spine texture analysis using trabecular bone score (TBS) is a risk factor for MOF and a risk factor for death in a retrospective cohort study from a large clinical registry for the province of Manitoba, Canada. FRAX® estimates the 10-year probability of major osteoporotic fracture (MOF) using clinical risk factors and femoral neck bone mineral density (BMD). Trabecular bone score (TBS), derived from texture in the spine dual X-ray absorptiometry (DXA) image, is related to bone microarchitecture and fracture risk independently of BMD. Our objective was to determine whether TBS provides information on MOF probability beyond that provided by the FRAX variables. We included 33,352 women aged 40-100years (mean 63years) with baseline DXA measurements of lumbar spine TBS and femoral neck BMD. The association between TBS, the FRAX variables, and the risk of MOF or death was examined using an extension of the Poisson regression model. During the mean of 4.7years, 1,754 women died and 1,872 sustained one or more MOF. For each standard deviation reduction in TBS, there was a 36% increase in MOF risk (HR 1.36, 95% CI 1.30-1.42, p < 0.001) and a 32% increase in death (HR 1.32, 95% CI 1.26-1.39, p < 0.001). When adjusted for significant clinical risk factors and femoral neck BMD, lumbar spine TBS was still a significant predictor of MOF (HR 1.18, 95% CI 1.12-1.23) and death (HR 1.20, 95% CI 1.14-1.26). Models for estimating MOF probability, accounting for competing mortality, showed that low TBS (10th percentile) increased risk by 1.5-1.6-fold compared with high TBS (90th percentile) across a broad range of ages and femoral neck T-scores. Lumbar spine TBS is able to predict incident MOF independent of FRAX clinical risk factors and femoral neck BMD even after accounting for the increased death hazard.

Systemic sclerosis (SSc) is associated with an increased risk of osteoporosis and fractures. To date, the etiology of bone loss in SSc is unclear. Trabecular bone score (TBS) provides an indirect measurement of bone microarchitecture, independent of areal bone mineral density (aBMD). The aims were to assess bone involvement in SSc using TBS in comparison with a "high-risk" population with rheumatoid arthritis (RA) and controls, and to investigate the determinants of a low TBS. This was a cross-sectional study of 65 women with SSc, 138 age-matched female patients with RA, and 227 age-matched female controls. Spine and hip aBMD were assessed using dual-energy X-ray absorptiometry. TBS was calculated from the anteroposterior image of the spine aBMD. TBS was significantly lower in SSc compared to controls (p < 0.0001) and did not differ from RA (p = 0.128), despite lower cumulative and daily glucocorticoid (GC) dose (p < 0.0001). Further, patients with SSc receiving GC ≥ 5 mg/day had a significantly lower TBS than those receiving GC < 5 mg/day (p = 0.001). Multivariate analysis revealed that a low TBS was independently associated with daily GC dose (OR 5.6, 95% CI 1.7-19.2) and a T score ≤ -2.5 SD (OR 5.0, 95% CI 1.5-7.0) in SSc. No association between GC and TBS was found in RA. Our results support the development of a combined approach using both TBS and aBMD for the assessment of bone microarchitecture in inflammatory rheumatic diseases. Our study showed that SSc-related bone involvement is characterized by an impairment in bone quality in addition to reduced bone quantity, and highlights that TBS can identify the negative effect of GC on bone microarchitecture.

(1) Background: Dual-energy X-ray absorptiometry (DXA)-based parameters such areal bone mineral density (aBMD) and Trabecular Bone Score (TBS) are routinely used to evaluate participants at risk for fragility fractures (FFs). We compared the accuracy of lumbar spine aBMD and TBS to that of volumetric BMD (vBMD) by quantitative computed tomography (QCT). (2) Methods: We conducted a retrospective analysis of participants who received both a DXA scan and a chest/abdomen CT scan. BMD and TBS values were obtained from lumbar DXA and vBMD values from QCT (three vertebrae from L1 to L4). T-score values were used for DXA diagnosis; the American College of Radiology ranges were used to diagnose bone status with QCT. (3) Results: We included 105 participants (87 women, mean age 69 ± 11 years). Among them, n = 49 (46.6%) presented at least one major FF. QCT diagnosis was as follows: osteoporosis = 59 (56.2%); osteopenia = 36 (34.3%); and normal status = 10 (9.5%). DXA diagnosis was osteoporosis = 25 (23.8%); osteopenia (33.3%) = 35; and normal status = 45 (42.9%). A total of 38 participants (36.2%) showed a TBS degraded microarchitecture. Correlation was moderate between aBMD and vBMD (r = 0.446), as well as between TBS and vBMD (r = 0.524). A good correlation was found between BMD and TBS (r = 0.621). ROC curves to discriminate between participants with/without FFs showed the following areas under the curve: 0.575 for aBMD, 0.650 for TBS, and 0.748 for QCT BMD. (4) Conclusions: QCT detected a higher prevalence of osteoporosis compared to DXA. TBS performed better than aBMD from DXA in discriminating between subjects with and without FFs.