Trabecular bone score in adults with type 1 diabetes: a meta-analysis.

Type 1 diabetes mellitus (T1DM) is associated with a disproportionately high fracture rate despite a minimal decrease in bone mineral density. Though trabecular bone score (TBS), an indirect measure of bone architecture, is lower in adults with T1DM, the modest difference is unlikely to account for the large excess risk and calls for further exploration. INTRODUCTION: Fracture rates in type 1 diabetes mellitus (T1DM) are disproportionately high compared to the modestly low bone mineral density (BMD). Distortion of bone microarchitecture compromises bone quality in T1DM and is indirectly measured by trabecular bone score (TBS). TBS could potentially be used as a screening tool for skeletal assessment; however, there are inconsistencies in the studies evaluating TBS in T1DM. We performed this meta-analysis to address this knowledge gap. METHODS: An electronic literature search was conducted using PubMed, Scopus, and Web of Science resources (all-year time span) to identify studies relating to TBS in T1DM. Cross-sectional and retrospective studies in adults with T1DM were included. TBS and BMD data were extracted for pooled analysis. Fracture risk could not be analyzed as there were insufficient studies reporting it. RESULT: Data from six studies were included (T1DM: n = 378 and controls: n = 286). Pooled analysis showed a significantly lower TBS [standardized mean difference (SMD) = - 0.37, 95% CI - 0.52 to - 0.21; p < 0.00001] in T1DM compared to controls. There was no difference in the lumbar spine BMD (6 studies, SMD - 0.06, 95% CI - 0.22 to 0.09; p = 0.43) and total hip BMD (6 studies, SMD - 0.17, 95% CI - 0.35 to 0.01; p = 0.06) in the case and control groups. CONCLUSIONS: Adults with T1DM have a lower TBS but similar total hip and lumbar spine BMD compared to controls. The risk attributable to the significant but limited difference in TBS falls short of explaining the large excess propensity to fragility fracture in adults with T1DM. Further studies on clarification of the mechanism and whether TBS is suited to screen for fracture risk in adults with T1DM are necessary.

Damaged bone microarchitecture by Trabecular Bone Score (TBS) and low appendicular muscle mass: main risk factors for vertebral and non-vertebral fractures in women with long-standing rheumatoid arthritis.

We ascertained the fracture risk factors stratified by vertebral and non-vertebral sites in rheumatoid arthritis (RA) females. Bone/muscle features, but not disease activity, were the main markers for fractures in this long-standing RA population: low trabecular bone score (TBS) for vertebral fracture and decreased appendicular muscle mass for non-vertebral fracture. PURPOSE: To assess risk factors for fractures, including clinical, laboratory and dual energy X-ray absorptiometry (DXA) parameters (bone mass, trabecular bone score-TBS, muscle mass) in women with established rheumatoid arthritis (RA). METHODS: Three hundred females with RA (ACR, 2010) were studied. Clinical data were obtained by questionnaire and disease activity by composite indices (DAS28, CDAI, SDAI), C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR). Bone mineral density (BMD), TBS, body composition and Vertebral Fracture Assessment (VFA) were performed by DXA. Logistic regression models were constructed to identify factors independently associated with vertebral (VF) and non-vertebral fractures (NVF), separately. RESULTS: Through rigorous eligibility criteria, a total of 265 women were yielded for final data analysis (median age, 55 [22-86] years; mean disease duration, 16.2 years). Prevalence of VF and NVF were 30.6% and 17.4%, respectively. In multivariate analyzes, TBS (OR = 1.6, 95%CI = 1.09-2.36, p = 0.017), CRP (OR = 1.54, 95%CI = 1.15-2.08, p = 0.004), and parathormone (OR = 1.24, 95%CI = 1.05-1.45, p = 0.009) were risk factors for VF, whereas low appendicular muscle mass (OR = 2.71; 95%CI = 1.01-7,28; p = 0.048), body mass index (BMI) (OR = 0.90, 95%CI = 0.82-0.99; p = 0.025), ESR (OR = 1.18, 95%CI = 1.01-1,38, p = 0,038) and hip BMD (OR = 1.82, 95%CI = 1.10-3.03, p = 0.02) were associated with NVF. CONCLUSION: In women with long-term RA, markers of fractures differed between distinct skeletal sites (vertebral and non-vertebral). The magnitude of association of bone/muscle parameters with fracture (TBS for VF and appendicular muscle mass for NVF) was greater than that of the association between RA activity and fracture. TBS seems to have greater discriminative power than BMD to identify subjects with VF in long-standing RA.

Evaluation of bone mineral density (BMD) and trabecular bone score (TBS) in pheochromocytoma and paraganglioma; a multi-centric case-control study from India.

Pheochromocytoma and paraganglioma (PPGL) have been associated with low bone mineral density (BMD) due to excess sympathetic system stimulation. Our study revealed low BMD and TBS (trabecular bone score) in cases compared to matched controls. Plasma-free nor-metanephrine and hypertension duration found to be most consistent predictive factors. PURPOSE: Pheochromocytoma and paraganglioma (PPGL) have been associated with low bone mineral density (BMD) and increased fracture risks. Sympathetic nervous system stimulation has been shown to increase bone resorption and decrease bone formation via ß2 receptors. Chronic inflammation and increased cytokine production add to more bone loss. TBS (trabecular bone score) is an established surrogate marker for bone histomorphometry. BMD and TBS data in pheochromocytoma and PPGL are scarce. The aim was to assess the BMD and TBS in pheochromocytoma and PPGL and look for clinical and biochemical predictors. METHODS: This case-control study had sample size of 58 (29 cases and controls each). BMI-, age-, and sex-matched controls were taken for comparison. Both cases and controls had undergone DXA scan and BMD {Z-scores and bone mineral concentration (BMC) in g/cm2} and TBS were analyzed. Detailed clinical histories and relevant biochemistry values were noted. RESULTS: The mean age of our case population was 29.5 ± 9.4 years with a mean age of HTN onset at 26.86 ± 6.6 years. Lumbar spine BMC (0.86 ± 0.14 vs 0.96 ± 0.15; p = 0.036), femoral neck Z-score (- 1.23 ± 1.07 vs - 0.75 ± 0.97; p = 0.003), and whole body BMC (0.91 ± 0.14 vs 1.07 ± 0.11; p = 0.000) were significantly low in cases compared to controls. Similarly, TBS was significantly lower in cases compared to controls (1.306 ± 0.113 vs 1.376 ± 0.083; p = 0.001). CONCLUSION: This study establishes both low bone mass and poor bone quality in an Indian pheochromocytoma and PPGL patient's cohort. Plasma-free nor-metanephrine and duration of hypertension were found to be most consistent predictive factors in multivariate regression analysis.

Bone Density and Trabecular Bone Score Decline Rapidly in the First Year After Bone Marrow Transplantation with a Marked Increase in 10-Year Fracture Risk.

As outcomes from allogeneic bone marrow transplantation (BMT) have improved, prevention of long-term complications, such as fragility fractures, has gained importance. We aimed to assess areal bone mineral density (aBMD) and trabecular bone score (TBS) changes post BMT, and determine their relationship with fracture prevalence. Patients who attended the Royal Melbourne Hospital (RMH) BMT clinic between 2005-2021 were included. Patient characteristics and dual-energy X-ray absorptiometry (DXA) values were collected from the electronic medical record and a survey. TBS iNsight™ was used to calculate TBS for DXA scans performed from 2019 onwards. 337 patients with sequential DXAs were eligible for inclusion. Patients were primarily male (60%) and mean age ± SD was 45.7 ± 13.4 years. The annualised decline in aBMD was greater at the femoral neck (0.066g/cm2 (0.0038-0.17)) and total hip (0.094g/cm2 (0.013-0.19)), compared to the lumbar spine (0.049g/cm2 (- 0.0032-0.16)), p < 0.0001. TBS declined independently of aBMD T-scores at all sites. Eighteen patients (5.3%) sustained 19 fractures over 3884 person-years of follow-up post-transplant (median follow-up 11 years (8.2-15)). This 5.3% fracture prevalence over the median 11-year follow-up period is higher than what would be predicted with FRAX® estimates. Twenty-two patients (6.5%) received antiresorptive therapy, and 9 of 18 (50%) who fractured received or were on antiresorptive therapy. In BMT patients, aBMD and TBS decline rapidly and independently in the first year post BMT. However, FRAX® fracture probability estimates incorporating these values significantly underestimate fracture rates, and antiresorptive treatment rates remain relatively low.

Glucagon-like Peptide-1 Receptor Agonists and Diabetic Osteopathy: Another Positive Effect of Incretines? A 12 Months Longitudinal Study.

Diabetic osteopathy is a frequent complication in patients with type 2 diabetes mellitus (T2DM). The association between T2DM and increased fracture risk has led to study the impact of new antidiabetic drugs on bone metabolism. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are incretin mimetic drugs which have many pleiotropic properties. The relationship between GLP-1RAs and bone is very complex: while in vitro and animal studies have demonstrated a protective effect on bone, human studies are scarce. We led a 12 months longitudinal study evaluating bone changes in 65 patients withT2DM for whom a therapy with GLP-1RAs had been planned. Fifty-four T2DM patients completed the 12-month study period; of them, 30 had been treated with weekly dulaglutide and 24 with weekly semaglutide. One-year therapy with GLP-1RAs resulted in a significant reduction in weight and BMI. Bone mineral density (BMD), bone metabolism, trabecular bone score (TBS), adiponectin, and myostatin were evaluated before and after 12 months of GLP-1RAs therapy. After 12 months of therapy bone turnover markers and adiponectin showed a significant increase, while myostatin values showed a modest but significant reduction. BMD-LS by DXA presented a significant reduction while the reduction in BMD-LS by REMS was not significant and TBS values showed a marginal increase. Both DXA and REMS techniques showed a modest but significant reduction in femoral BMD. In conclusion, the use of GLP-1RAs for 12 months preserves bone quality and reactivates bone turnover. Further studies are needed to confirm whether GLP-1RAs could represent a useful therapeutic option for patients with T2DM and osteoporosis.

Chemical Shift-Encoded MRI of the Lumbar Vertebral Bone Marrow for Detecting Osteoporosis With Low Trabecular Bone Quality in Patients With Breast Cancer Receiving Aromatase Inhibitors.

BACKGROUND: Osteoporosis with low trabecular bone quality (OLB) in patients with breast cancer receiving aromatase inhibitor (AI) therapy is associated with an increased risk of vertebral fractures. The capability of chemical shift-encoded MRI (CSE-MRI) in detecting OLB needs to be investigated. PURPOSE: To assess the diagnostic performance of proton density fat fraction (PDFF) and R2* measurements from CSE-MRI for detecting OLB in postmenopausal women with breast cancer undergoing AI therapy. STUDY TYPE: Prospective. POPULATION: 126 postmenopausal females (mean age: 69.5 ± 8.8 years) receiving AIs (average period: 41.6 ± 26.5 months) after breast cancer surgery. FIELD STRENGTH/SEQUENCE: 1.5-T, three-dimensional CSE-MRI (six echoes), T1-weighted Dixon, short tau inversion recovery, and diffusion-weighted images. ASSESSMENT: Both CSE-MRI and dual-energy x-ray absorptiometry were performed on the same day. Measurements included averaged PDFF, R2*, bone mineral density (BMD), and trabecular bone score (TBS) from L1 to L4 vertebrae. A T-score ≤ -2.5 from BMD measurements indicated osteoporosis, whereas T-scores of ≤ - 2.5 plus TBS ≤-3.7 indicated OLB. The diagnostic performance of PDFF, R2*, and the combination of PDFF and R2* for identifying osteoporosis or OLB was assessed. STATISTICAL TESTS: Student's t-test; Mann-Whitney U test; χ2 or Fisher exact tests; Pearson correlation; multivariate analysis; Receiver operating characteristic (ROC) analysis with the area under the curve (AUC); logistic regression model; intraclass correlation coefficient. A P-value <0.05 was considered statistically significant. RESULTS: For detecting osteoporosis, AUC values were 0.59 (PDFF), 0.66 (R2*), and 0.65 (combined PDFF and R2*). Significant mean differences were noted between patients with and without OLB for PDFF (66.11 ± 5.36 vs. 57.49 ± 6.43) and R2* (46.62 ± 9.24 vs. 63.36 ± 12.44). AUC values for detecting OLB were 0.75 (PDFF), 0.82 (R2*), and 0.84 (combined PDFF and R2*). DATA CONCLUSION: R2* may perform better than PDFF for identifying OLB in patients with breast cancer receiving AIs. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 4.

Association of bone mineral density and potential risk factors for osteoporosis in patients with severe haemophilia A.

INTRODUCTION: In people with haemophilia (PWH), recurrent episodes of bleeding lead to joint deterioration and bone resorption. To date, the effects of various other factors on bone mineral density (BMD) reduction have found conflicting results. AIM: The aim of this study was to analyse the relationships between BMD, bone mineral content (BMC), and trabecular bone score (TBS) parameters based on the dual X-ray absorptiometry method (DXA) and potential risk factors for osteoporosis in patients with severe haemophilia A. METHODS: Fifty-five men with severe haemophilia A, aged 18-68 years, and 59 healthy volunteer men were enrolled in this study. Densitometric-derived lumbar spine and femoral neck BMD, BMC, and TBS were measured. Blood analyses were performed for morphology parameters, liver and kidney function parameters, and viral status. Serum levels of oestradiol (E2 ), testosterone (T), dehydroepiandrosterone sulphate (DHEA-S), parathormone, and vitamin D were measured. RESULTS: Patients showed significantly lower BMD compared to controls (p < .003). The result below the expected range for age was nearly double (6.82% vs. 3.92%) in PWH under 50 years old compared to controls. Haemophilic patients also exhibited significantly higher vitamin D3 deficiency (p < .0001), which was strongly associated with low TBS. Additionally, low body mass index and high neutrophil/lymphocyte ratio were correlated with low BMC and BMD. CONCLUSIONS: This study confirms the prevalence of low BMD and BMC in patients with haemophilia in Poland. Factors that contribute to low BMD are primarily vitamin D deficiency, low BMI, high neutrophil/lymphocyte ratio, and low testosterone/oestradiol ratio.

Can TBS reference values be a valid indicator for clinical vertebral fracture? A cross-sectional study.

INTRODUCTION: Trabecular bone score (TBS) is partially independent of fracture risk. Reference values for TBS have not been established in official guidelines, and thus clinicians often have difficulty interpreting TBS results. This study aimed to investigate whether reference values for TBS could be a valid indicator for clinical vertebral fracture (CVF). MATERIALS AND METHODS: This cross-sectional study involved 231 women with CVF and 563 women without CVF aged 60-90 years who underwent dual-energy X-ray absorptiometry during 2019-2023. They were divided into osteoporosis, osteopenia, and normal groups according to bone mineral density of the lumbar spine. Reference values for TBS were defined as low (≤ 1.23), intermediate (1.23-1.31), and high (≥ 1.31). RESULTS: Among patients without anti-osteoporosis treatment (n = 476), the proportion with low TBS was 36.7% in the CVF group and 10.7% in the control group. The proportion with CVF was higher in the low TBS group than in the intermediate and high TBS groups, especially in the osteoporosis group (p < 0.001). The odds ratio for CVF was higher in the low TBS group than in the intermediate and high especially in patients with normal BMD and osteoporosis. The TBS cut-off values for incidence of CVF in the osteoporosis, osteopenia, and normal groups were 1.224, 1.319, and 1.322, respectively. CONCLUSIONS: The reference value for low TBS (≤ 1.23) was useful as an indicator for CVF, especially in patients with osteoporosis. It is expected that reference values for TBS will be established in official guidelines in the future.

Mechanisms of osteoporosis associated with chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is a disease characterized by chronic respiratory symptoms due to inflammatory and destructive changes of the lung leading to progressive airflow obstruction. Fragility fractures associated with osteoporosis are among major comorbidities and have significant impacts on quality of life and prognosis of patients with COPD. Evidence suggests that both decreased bone mineral density (BMD) and impaired bone quality contribute to bone fragility and resultant fractures in COPD. Although various clinical risk factors of osteoporosis have been described, mechanisms of COPD-associated osteoporosis are still largely unknown. In addition, its specific treatment has not been established, either. Previous studies have suggested involvement of low BMI and sarcopenia in the pathogenesis of COPD-associated osteoporosis. In this narrative review, we will propose critical roles of vitamin D deficiency and inflammation, both of which are often present in COPD and may underlie the development of osteosarcopenia and impaired bone quality, ultimately causing fractures in COPD patients.

Primary Hyperparathyroidism: Assessment of the Effects of Parathyroidectomy Using Dual X-Ray Absorptiometry, Trabecular Bone Score, and Dual X-Ray Absorptiometry-Based Three-Dimensional Modeling.

OBJECTIVE: This study aimed to evaluate the bone microstructure to determine whether curative surgery of primary hyperparathyroidism produces changes in bone mineral density (BMD), trabecular bone score (TBS), and three-dimensional (3D) dual x-ray absorptiometry (DXA) parameters and whether these changes are comparable. METHODS: We retrospectively studied 85 patients (60 women and 25 men, 60.4 ± 12.5 years) diagnosed with primary hyperparathyroidism and undergoing parathyroidectomy. Mean percent changes in BMD (lumbar spine [LS], femoral neck [FN], total hip [TH], and 1/3 radius), TBS and 3D-DXA parameters (trabecular volumetric BMD (vBMD), cortical vBMD, integral vBMD, cortical surface density (sBMD), and cortical thickness at TH) after surgery (12, 24, and/or 36 months) were calculated and compared, and we sought the determinants of these changes. RESULTS: After parathyroidectomy, BMD presented statistically significant mean increases in LS, FN, and TH during the first 3 years after surgery (P < .001), accompanied by an improvement in all 3D-DXA parameters, but there were no significant changes in 1/3 radius BMD or TBS. Cortical sBMD, trabecular vBMD, and integral vBMD reached mean increases of similar magnitude to those of FN and TH BMD. Age and preoperative serum levels of parathyroid hormone and carboxy-terminal telopeptide of type 1 collagen were significantly associated with percent changes after surgery. CONCLUSION: We found a benefit of parathyroidectomy for bone, with significant percent increases in LS, FN, and TH BMD up to the third year after surgery, and a qualitative benefit for the hip in both its trabecular and cortical compartments and bone strength.

Denosumab improves trabecular bone score in relationship with decrease in fracture risk of women exposed to aromatase inhibitors.

PURPOSE: Trabecular bone score (TBS) is a gray-level textural metric that has shown to correlate with risk of fractures in several forms of osteoporosis. The value of TBS in predicting fractures and the effects of bone-active drugs on TBS in aromatase inhibitors (AIs)-induced osteoporosis are still largely unknown. The primary objective of this retrospective study was to assess the effects of denosumab and bisphosphonates (BPs) on TBS and vertebral fractures (VFs) in women exposed to AIs. METHODS: 241 consecutive women (median age 58 years) with early breast cancer undergoing treatment with AIs were evaluated for TBS, bone mineral density (BMD) and morphometric VFs at baseline and after 18-24 months of follow-up. During the study period, 139 women (57.7%) received denosumab 60 mg every 6 months, 53 (22.0%) BPs, whereas 49 women (20.3%) were not treated with bone-active drugs. RESULTS: Denosumab significantly increased TBS values (from 1.270 to 1.323; P < 0.001) accompanied by a significant decrease in risk of VFs (odds ratio 0.282; P = 0.021). During treatment with BPs, TBS did not significantly change (P = 0.849) and incidence of VFs was not significantly different from women untreated with bone-active drugs (P = 0.427). In the whole population, women with incident VFs showed higher decrease in TBS vs. non-fractured women (P = 0.003), without significant differences in changes of BMD at any skeletal site. CONCLUSIONS: TBS variation predicts fracture risk in AIs treated women. Denosumab is effective to induce early increase of TBS and reduction in risk of VFs.

Executive Summary of the 2023 Adult Position Development Conference of the International Society for Clinical Densitometry: DXA Reporting, Follow-up BMD Testing and Trabecular Bone Score Application and Reporting.

After 15 months of preparation by task force chairs and teams, ISCD's 9th Position Development Conference (PDC) convened in Northbrook, IL, USA on March 28th and 29th, 2023 to approve new ISCD Official Positions in the topic areas of DXA Reporting, Follow-up BMD Testing and TBS Application and Reporting. Three teams of participants work to bring the PDC to fruition: the Steering Committee, Task Forces and Chairs, and the Expert Panel. To reach agreement on draft Official Positions, the PDC follows a scripted process with the UCLA/RAND Appropriateness Method (UCLA/RAM) as its foundation. Multiple rounds of data review, public debate and voting resulted in 32 new or modified Official Positions. Six companion position papers are also published along with this Executive Summary, serving as the detailed substantiation for the Official Positions. This Executive Summary reviews the personnel groups, activities and products of the 2023 PDC, with the entirety of the updated 2023 Official Positions presented in Appendix A. New Official Positions are highlighted in bold.

Osteoporosis and Osteopenia in patients with psoriatic arthritis: a single-center retrospective study.

OBJECTIVE: It is known that fracture risk is increased in patients with psoriatic arthritis (PsA), however, there is no consensus on the association with osteoporosis. The purpose of this study was to elicit the rate of osteoporosis and the risk factors of osteoporosis in patients with PsA at our institution. METHODS: The data in this study were extracted from 163 patients with PsA. Osteoporosis and osteopenia were defined based on the WHO definition. Osteoporosis was also diagnosed when a fragility vertebral compression fracture was observed. RESULTS: The osteoporosis and osteopenia rates for PsA patients were 11.7% and 33.1%, respectively. The rates of osteoporosis and osteopenia in males were particularly high compared to previous reports, at 9.3% and 34.3%, respectively. Trabecular bone score (TBS) was considered age-appropriate for both males and females. Body mass index (BMI) and TBS were significantly lower in patients with osteoporosis. CONCLUSIONS: In patients with PsA, males are at elevated risk of osteoporosis and associated fragility fractures even if they are under 50 years old. BMI was significantly lower in osteoporotic cases, suggesting the importance of bone mineral density testing and treatment in such cases.

Trabecular bone score and bone mineral density as indices of skeletal fragility in endogenous Cushing's syndrome.

OBJECTIVE: Endogenous Cushing's syndrome (CS) is a known cause of secondary osteoporosis. Vertebral fractures (VFs) in endogenous CS may occur despite normal bone mineral density (BMD). Trabecular bone score (TBS) is a relatively new, non-invasive technique to assess bone microarchitecture. The objective of our study was to analyse the BMD and bone microarchitecture using TBS in endogenous CS and compare it with a group of age and sex-matched healthy controls, and also analyse the factors predicting BMD and TBS. DESIGN: Cross-sectional study of cases and controls. PATIENTS AND MEASUREMENTS: We included 40 female patients with overt endogenous CS, out of which 32 were adrenocorticotropic hormone (ACTH)-dependent CS and 8 were ACTH-independent. We also included 40 healthy, female controls. Both patients and controls were subjected to an assessment of biochemical parameters and BMD and TBS. RESULTS: Patients with endogenous CS had significantly lower BMD at the lumbar spine, femoral neck, and total hip and significantly lower TBS than healthy controls (all p < .001), while no significant difference was noted in the distal radius BMD (p = .055). In endogenous CS, a large proportion of patients, n = 13 (32.5%) had normal BMD for age (BMD Z-score ≥ -2.0) with low TBS (L1 -L4 TBS ≤ 1.34). TBS correlated negatively with HbA1c (p = .006), and positively with serum T4 (p = .027). CONCLUSION: TBS should be considered an important complementary tool in addition to BMD for the routine assessment of skeletal health in CS.

Update on the clinical use of trabecular bone score (TBS) in the management of osteoporosis: results of an expert group meeting organized by the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO), and the International Osteoporosis Foundation (IOF) under the auspices of WHO Collaborating Center for Epidemiology of Musculoskeletal Health and Aging.

PURPOSE: Trabecular bone score (TBS) is a grey-level textural measurement acquired from dual-energy X-ray absorptiometry lumbar spine images and is a validated index of bone microarchitecture. In 2015, a Working Group of the European Society on Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO) published a review of the TBS literature, concluding that TBS predicts hip and major osteoporotic fracture, at least partly independent of bone mineral density (BMD) and clinical risk factors. It was also concluded that TBS is potentially amenable to change as a result of pharmacological therapy. Further evidence on the utility of TBS has since accumulated in both primary and secondary osteoporosis, and the introduction of FRAX and BMD T-score adjustment for TBS has accelerated adoption. This position paper therefore presents a review of the updated scientific literature and provides expert consensus statements and corresponding operational guidelines for the use of TBS. METHODS: An Expert Working Group was convened by the ESCEO and a systematic review of the evidence undertaken, with defined search strategies for four key topics with respect to the potential use of TBS: (1) fracture prediction in men and women; (2) initiating and monitoring treatment in postmenopausal osteoporosis; (3) fracture prediction in secondary osteoporosis; and (4) treatment monitoring in secondary osteoporosis. Statements to guide the clinical use of TBS were derived from the review and graded by consensus using the Grades of Recommendation, Assessment, Development and Evaluation (GRADE) approach. RESULTS: A total of 96 articles were reviewed and included data on the use of TBS for fracture prediction in men and women, from over 20 countries. The updated evidence shows that TBS enhances fracture risk prediction in both primary and secondary osteoporosis, and can, when taken with BMD and clinical risk factors, inform treatment initiation and the choice of antiosteoporosis treatment. Evidence also indicates that TBS provides useful adjunctive information in monitoring treatment with long-term denosumab and anabolic agents. All expert consensus statements were voted as strongly recommended. CONCLUSION: The addition of TBS assessment to FRAX and/or BMD enhances fracture risk prediction in primary and secondary osteoporosis, adding useful information for treatment decision-making and monitoring. The expert consensus statements provided in this paper can be used to guide the integration of TBS in clinical practice for the assessment and management of osteoporosis. An example of an operational approach is provided in the appendix. This position paper presents an up-to-date review of the evidence base, synthesised through expert consensus statements, which informs the implementation of Trabecular Bone Score in clinical practice.

Romosozumab is associated with greater trabecular bone score improvement compared to denosumab in postmenopausal osteoporosis.

In this study, romosozumab demonstrated significantly greater improvement in trabecular bone score compared to denosumab therapy in postmenopausal women previously treated with antiresorptive agents. Notably, in patients previously treated with anti-resorptive agents, treatment with romosozumab resulted in similar increases in trabecular bone score compared to that of drug-naïve patients. PURPOSE: Romosozumab significantly increases bone mineral density (BMD) and rapidly reduces fracture risk. Whether romosozumab can improve the spinal trabecular bone score (TBS) as a bone quality indicator merits further investigation. METHODS: Data for postmenopausal women starting romosozumab or denosumab treatment at Severance Hospital, Korea, were analyzed. Romosozumab and denosumab groups were 1:1 matched using propensity scores, considering relevant covariates. Good responders were defined as those with TBS improvement of 5.8% or greater. RESULTS: Overall, 174 patients (romosozumab, n = 87; denosumab, n = 87) were analyzed. Matched groups did not differ in age (64 years), weight, height, previous fracture (38%), lumbar spine or femoral neck BMD (T-score, -3.4 and -2.6, respectively), or prior bisphosphonate or selective estrogen receptor modulator (SERM) exposure (50%). The romosozumab group exhibited a greater increase in lumbar spine BMD (15.2% vs. 6.9%, p < 0.001) and TBS (3.7% vs. 1.7%, p = 0.013) than the denosumab group. In patients transitioning from bisphosphonate or SERM, romosozumab users showed greater improvement in TBS compared to denosumab users (3.9% versus 0.8%, P = 0.006); the drug-naive group showed no significant difference (3.6% versus 2.7%, P = 0.472). The romosozumab group had a higher proportion of good responders than the denosumab group (33.3% vs. 18.4%, p = 0.024). Romosozumab therapy for 12 months resulted in 3.8-fold higher odds of a good response in TBS than denosumab after covariate adjustment (adjusted odds ratio 3.85, p = 0.002). CONCLUSION: Romosozumab could improve bone mass and bone quality, measured by TBS, in postmenopausal osteoporosis, particularly as a subsequent regimen in patients previously taking anti-resorptive agents.

Bone density and trabecular bone score to predict fractures in adults aged 20-39 years: a registry-based study.

Trabecular bone score (TBS) enhances fracture risk assessment in older adults; whether this is true in younger people is uncertain. In this registry-based study of adults aged 20-39 years, low BMD, but not low TBS, predicted fracture. PURPOSE: Trabecular bone score (TBS), a bone texture measurement, is associated with fracture risk independent of bone mineral density (BMD) in older adults. In adults aged 20-40 years, TBS remains stable and its role in fracture risk assessment is unclear. We utilized the Manitoba Bone Density Registry to explore the relationship of fracture risk with BMD and TBS in younger adults. METHODS: Women and men aged 20-39 years referred for DXA testing were studied. Incident major and any fractures were captured from health records. Categories based on WHO BMD T-score classification and TBS tertile were considered using Cox regression models to estimate covariate-adjusted (including sex) hazard ratios (aHR, 95%CI) for incident fracture by category, and each SD decrement in BMD and TBS. RESULTS: The study included 2799 individuals (77% female, mean age 32 years). Mean (SD) minimum T-score was - 0.9 (1.1) and TBS 1.355 (0.114); 7% had osteoporosis and 13% were in the lowest TBS tertile. Incident major osteoporotic fracture (MOF) and any fracture risk was elevated in those with osteopenia (aHRs 1.20/1.45) and osteoporosis (aHRs 4.60/5.16). Fracture risk was unrelated to TBS tertile. Each SD decrement in BMD was associated with increased MOF risk (aHR 1.64) and any fracture (aHR 1.71); lower TBS was unrelated to fractures. CONCLUSION: In young adults, low BMD, but not low TBS, was predictive of MOF and any fracture. Routine clinical TBS measurement is not recommended for young adults. Further study is indicated to evaluate whether TBS is beneficial in subsets of younger adults.

Heel quantitative ultrasound (QUS) predicts incident fractures independently of trabecular bone score (TBS), bone mineral density (BMD), and FRAX: the OsteoLaus Study.

This study aimed to better define the role of heel-QUS in fracture prediction. Our results showed that heel-QUS predicts fracture independently of FRAX, BMD, and TBS. This corroborates its use as a case finding/pre-screening tool in osteoporosis management. INTRODUCTION: Quantitative ultrasound (QUS) characterizes bone tissue based on the speed of sound (SOS) and broadband ultrasound attenuation (BUA). Heel-QUS predicts osteoporotic fractures independently of clinical risk factors (CRFs) and bone mineral density (BMD). We aimed to investigate whether (1) heel-QUS parameters predict major osteoporotic fractures (MOF) independently of the trabecular bone score (TBS) and (2) the change of heel-QUS parameters over 2.5 years is associated with fracture risk. METHODS: One thousand three hundred forty-five postmenopausal women from the OsteoLaus cohort were followed up for 7 years. Heel-QUS (SOS, BUA, and stiffness index (SI)), DXA (BMD and TBS), and MOF were assessed every 2.5 years. Pearson's correlation and multivariable regression analyses were used to determine associations between QUS and DXA parameters and fracture incidence. RESULTS: During a mean follow-up of 6.7 years, 200 MOF were recorded. Fractured women were older, more treated with anti-osteoporosis medication; had lower QUS, BMD, and TBS; higher FRAX-CRF risk; and more prevalent fractures. TBS was significantly correlated with SOS (0.409) and SI (0.472). A decrease of one SD in SI, BUA or SOS increased the MOF risk by (OR(95%CI)) 1.43 (1.18-1.75), 1.19 (0.99-1.43), and 1.52 (1.26-1.84), respectively, after adjustment for FRAX-CRF, treatment, BMD, and TBS. We found no association between the change of QUS parameters in 2.5 years and incident MOF. CONCLUSION: Heel-QUS predicts fracture independently of FRAX, BMD, and TBS. Thus, QUS represents an important case finding/pre-screening tool in osteoporosis management. The change in QUS over time was not associated with future fractures, making it inappropriate for patient monitoring.

Long-term effect of denosumab on bone microarchitecture as assessed by tissue thickness-adjusted trabecular bone score in postmenopausal women with osteoporosis: results from FREEDOM and its open-label extension.

In postmenopausal women with osteoporosis, up to 10 years of denosumab treatment significantly and continuously improved bone microarchitecture assessed by tissue thickness-adjusted trabecular bone score, independently of bone mineral density. Long-term denosumab treatment decreased the number of high fracture-risk patients and shifted more patients to lower fracture-risk categories. PURPOSE: To investigate the long-term effect of denosumab on bone microarchitecture assessed by tissue thickness-adjusted trabecular bone score (TBSTT) in post-hoc subgroup analysis of FREEDOM and open-label extension (OLE). METHODS: Postmenopausal women with lumbar spine (LS) or total hip BMD T-score <-2.5 and ≥-4.0 who completed the FREEDOM DXA substudy and continued in OLE were included. Patients received either denosumab 60 mg subcutaneously every 6 months for 3 years and same-dose open-label denosumab for 7 years (long-term denosumab; n=150) or placebo for 3 years and open-label denosumab for 7 years (crossover denosumab; n=129). BMD and TBSTT were assessed on LS DXA scans at FREEDOM baseline, month 1, and years 1-6, 8, and 10. RESULTS: In long-term denosumab group, continued increases from baseline to years 4, 5, 6, 8, and 10 in BMD (11.6%, 13.7%, 15.5%, 18.5%, and 22.4%) and TBSTT (3.2%, 2.9%, 4.1%, 3.6%, and 4.7%) were observed (all P < 0.0001). Long-term denosumab treatment decreased the proportion of patients at high fracture-risk (according to TBSTT and BMD T-score) from baseline up to year 10 (93.7 to 40.4%), resulting in increases in the proportions at medium-risk (6.3 to 53.9%) and low-risk (0 to 5.7%) (P < 0.0001). Similar responses were observed in crossover denosumab group. Changes in BMD and TBSTT were poorly correlated during denosumab treatment. CONCLUSION: In postmenopausal women with osteoporosis, up to 10 years of denosumab significantly and continuously improved bone microarchitecture assessed by TBSTT, independently of BMD, and shifted more patients to lower fracture-risk categories.

Trabecular Bone Score as an Index of Bone Fragility in Patients with Acromegaly: A Systematic Review and Meta-Analysis.

BACKGROUND: Acromegaly is characterized by impaired bone quality and increased fracture risk. However, due to the pathophysiology of acromegalic osteopathy, bone mineral density (BMD) does not represent a reliable predictor for fragility fractures in this setting. Trabecular bone score (TBS) has been recently evaluated as an alternative index of skeletal fragility in acromegalic patients. However, no conclusive data are still available in this regard. METHODS: PubMed/Medline, EMBASE, Cochrane Library, Ovid, and CINAHL databases were systematically searched until June 2022 for studies reporting data either about the comparison of TBS values between acromegalic patients and non-acromegalic controls or about the relationship - within acromegalic patients - between TBS values and fracture risk. Effect sizes were pooled through a random-effect model. RESULTS: Eight studies were eligible for inclusion in the meta-analysis, encompassing 336 acromegalic patients and 490 non-acromegalic controls. Overall, TBS was significantly lower in acromegalic patients compared to controls (-0.089, 95% CI: [-0.111, -0.067], p < 0.01), irrespective of acromegaly disease activity and gonadal status. With respect to fracture risk, TBS was significantly lower in acromegalic patients with vertebral fractures than in those without (-0.099, 95% CI: [-0.166, -0.032], p < 0.01). CONCLUSION: In this meta-analysis, we specifically assessed the role of TBS as an index of bone quality and fracture risk in patients with acromegaly. Our results support the notion that TBS could be of value in the assessment and management of skeletal fragility in acromegalic patients, especially in light of the poor information provided in this setting by BMD.