Effect of Abdominal Tissue Thickness on Trabecular Bone Score and Fracture Risk in Adults With Diabetes: The Manitoba BMD Registry.

Individuals with type 2 diabetes have lower trabecular bone score (TBS) and increased fracture risk despite higher bone mineral density (BMD). However, measures of trabecular microarchitecture from high resolution peripheral computed tomography (HRpQCT) are not lower in type 2 diabetes. We hypothesized that confounding effects of abdominal tissue thickness may explain this discrepancy, since central obesity is a risk factor for diabetes and also artifactually lowers TBS. This hypothesis was tested in individuals aged 40 years and older from a large DXA registry, stratified by sex and diabetes status. When DXA-measured abdominal tissue thickness was not included as a covariate, men without diabetes had lower TBS than women without diabetes (mean difference -0.074, p<0.001). TBS was lower in women with versus without diabetes (mean difference -0.037, p<0.001), and men with versus without diabetes (mean difference -0.007, p=0.042). When adjusted for tissue thickness these findings reversed, and TBS became greater in men versus women without diabetes (mean difference +0.053, p<0.001), in women with versus without diabetes (mean difference +0.008, p<0.001) and in men with versus without diabetes (mean difference +0.014, p<0.001). During mean 8.7 years observation, incident major osteoporotic fractures were seen in 7048 (9.6%). Adjusted for multiple covariates except tissue thickness, TBS predicted fracture in all subgroups with no significant diabetes interaction. When further adjusted for tissue thickness, HR per SD lower TBS remained significant and even increased slightly. In conclusion, TBS predicts fractures independent of other clinical risk factors in both women and men, with and without diabetes. Excess abdominal tissue thickness in men and individuals with type 2 diabetes may artifactually lower TBS using the current algorithm, which reverses after accounting for tissue thickness. This supports ongoing efforts to update the TBS algorithm to directly account for the effects of abdominal tissue thickness for improved fracture risk prediction.

Individuals with type 2 diabetes are at increased fracture risk despite having higher bone mineral density (BMD). Previous studies suggest that trabecular bone score (TBS), a measure of bone derived from spine DXA images that can be used to assess fracture risk in addition to BMD, may be lower in individuals with type 2 diabetes. However, TBS is artificially lowered by greater abdominal obesity. We showed that abdominal obesity explained the lower TBS measurements that were seen in individuals with type 2 diabetes. However, even when we considered the effect of abdominal obesity, TBS was still able to predict major fractures in both women and men, with and without diabetes.

Periprosthetic fractures are osteoporotic fractures: missed opportunities for osteoporosis diagnosis.

Joint replacement surgery is common in older adults, leading to increasing periprosthetic fracture (PPFx) occurrence. We reviewed all PPFx seen over a 4-year period at an academic hospital. Clinical osteoporosis could be diagnosed based on existing data in 104 (67%) at the time of PPFx. Periprosthetic fractures are generally osteoporosis-related. PURPOSE: Periprosthetic fractures (PPFx) cause morbidity, mortality, and cost. This study's purpose was to describe osteoporosis-related data available at the time of PPFx. METHODS: The electronic medical record (EMR) of PPFx patients seen over 4 years in a university orthopedic practice were reviewed. Demographic data and osteoporosis relevant parameters were collected. Prior DXA studies were reviewed, and L1 Hounsfield unit (HU) measurements were performed on CT scans obtained within 2 years before PPFx. Clinical osteoporosis was defined as prior diagnosis, prescribed osteoporosis treatment, T-score ≤ - 2.5, HU ≤ 100, or prior fracture. RESULTS: Records of 156 PPFx patients (115 F/41 M), mean (SD) age 75.4 (11.9), were reviewed. Almost all 153/156 (98%) of these fractures were femoral. Falls caused 139 (89%); 12 (8%) were spontaneous. Mean time post-arthroplasty was 7.9 (6.3) years. Prior fragility fracture(s) occurred in 72 (46%); 14 were PPFx. Osteoporosis was previously diagnosed in 45 (29%) and medications prescribed in 41 (26%). Prior to PPFx, DXA data were available in 62, mean (SD) lowest T-score was - 1.9 (0.9) and was ≤ - 2.5 in 19. CT data were available in 46; mean (SD) L1 HU was 79.0 (29.4) and was ≤ 100 in 35. Based on existing data, clinical osteoporosis could have been diagnosed in 104 (67%) at the time of PPFx. CONCLUSION: Periprosthetic fractures are osteoporosis-related. They occur in older adults, often female, and result from falls; BMD, when assessed, is low. Data available at the time of PPFx often allows osteoporosis diagnosis; this should prompt evaluation and pharmacologic treatment consideration.

Consensus Statement on Vitamin D Status Assessment and Supplementation: Whys, Whens, and Hows.

The 6th International Conference, "Controversies in Vitamin D," was convened to discuss controversial topics, such as vitamin D metabolism, assessment, actions, and supplementation. Novel insights into vitamin D mechanisms of action suggest links with conditions that do not depend only on reduced solar exposure or diet intake and that can be detected with distinctive noncanonical vitamin D metabolites. Optimal 25-hydroxyvitamin D (25(OH)D) levels remain debated. Varying recommendations from different societies arise from evaluating different clinical or public health approaches. The lack of assay standardization also poses challenges in interpreting data from available studies, hindering rational data pooling and meta-analyses. Beyond the well-known skeletal features, interest in vitamin D's extraskeletal effects has led to clinical trials on cancer, cardiovascular risk, respiratory effects, autoimmune diseases, diabetes, and mortality. The initial negative results are likely due to enrollment of vitamin D-replete individuals. Subsequent post hoc analyses have suggested, nevertheless, potential benefits in reducing cancer incidence, autoimmune diseases, cardiovascular events, and diabetes. Oral administration of vitamin D is the preferred route. Parenteral administration is reserved for specific clinical situations. Cholecalciferol is favored due to safety and minimal monitoring requirements. Calcifediol may be used in certain conditions, while calcitriol should be limited to specific disorders in which the active metabolite is not readily produced in vivo. Further studies are needed to investigate vitamin D effects in relation to the different recommended 25(OH)D levels and the efficacy of the different supplementary formulations in achieving biochemical and clinical outcomes within the multifaced skeletal and extraskeletal potential effects of vitamin D.

Fully automated CT imaging biomarkers for opportunistic prediction of future hip fractures.

OBJECTIVE: Assess automated CT imaging biomarkers in patients who went on to hip fracture, compared with controls. METHODS: In this retrospective case-control study, 6926 total patients underwent initial abdominal CT over a 20-year interval at one institution. A total of 1308 patients (mean age at initial CT, 70.5 ± 12.0 years; 64.4% female) went on to hip fracture (mean time to fracture, 5.2 years); 5618 were controls (mean age 70.3 ± 12.0 years; 61.2% female; mean follow-up interval 7.6 years). Validated fully automated quantitative CT algorithms for trabecular bone attenuation (at L1), skeletal muscle attenuation (at L3), and subcutaneous adipose tissue area (SAT) (at L3) were applied to all scans. Hazard ratios (HRs) comparing highest to lowest risk quartiles and receiver operating characteristic (ROC) curve analysis including area under the curve (AUC) were derived. RESULTS: Hip fracture HRs (95% CI) were 3.18 (2.69-3.76) for low trabecular bone HU, 1.50 (1.28-1.75) for low muscle HU, and 2.18 (1.86-2.56) for low SAT. 10-year ROC AUC values for predicting hip fracture were 0.702, 0.603, and 0.603 for these CT-based biomarkers, respectively. Multivariate combinations of these biomarkers further improved predictive value; the 10-year ROC AUC combining bone/muscle/SAT was 0.733, while combining muscle/SAT was 0.686. CONCLUSION: Opportunistic use of automated CT bone, muscle, and fat measures can identify patients at higher risk for future hip fracture, regardless of the indication for CT imaging. ADVANCES IN KNOWLEDGE: CT data can be leveraged opportunistically for further patient evaluation, with early intervention as needed. These novel AI tools analyse CT data to determine a patient's future hip fracture risk.

Clinical Use of Trabecular Bone Score: The 2023 ISCD Official Positions.

Osteoporosis can currently be diagnosed by applying the WHO classification to bone mineral density (BMD) assessed by dual-energy x-ray absorptiometry (DXA). However, skeletal factors other than BMD contribute to bone strength and fracture risk. Lumbar spine TBS, a grey-level texture measure which is derived from DXA images has been extensively studied, enhances fracture prediction independent of BMD and can be used to adjust fracture probability from FRAX® to improve risk stratification. The purpose of this International Society for Clinical Densitometry task force was to review the existing evidence and develop recommendations to assist clinicians regarding when and how to perform, report and utilize TBS. Our review concluded that TBS is most likely to alter clinical management in patients aged ≥ 40 years who are close to the pharmacologic intervention threshold by FRAX. The TBS value from L1-L4 vertebral levels, without vertebral exclusions, should be used to calculate adjusted FRAX probabilities. L1-L4 vertebral levels can be used in the presence of degenerative changes and lumbar compression fractures. It is recommended not to report TBS if extreme structural or pathological artifacts are present. Monitoring and reporting TBS change is unlikely to be helpful with the current version of the TBS algorithm. The next version of TBS software will include an adjustment based upon directly measured tissue thickness. This is expected to improve performance and address some of the technical factors that affect the current algorithm which may require modifications to these Official Positions as experience is acquired with this new algorithm.

Effect of Romosozumab Treatment in Postmenopausal Women With Osteoporosis and Knee Osteoarthritis: Results From a Substudy of a Phase 3 Clinical Trial.

OBJECTIVE: Romosozumab is a bone-forming agent approved for osteoporosis treatment. Here we report results of the protocol-specified, noninferiority osteoarthritis substudy of the fracture study in postmenopausal women with osteoporosis (FRAME), which evaluated the effect of romosozumab versus placebo on knee osteoarthritis in patients with a clinical history of osteoarthritis. METHODS: Women in FRAME with a history of knee osteoarthritis were eligible for enrollment in the osteoarthritis substudy; key inclusion criteria were osteoarthritis-related signal knee pain, morning stiffness lasting less than 30 minutes, knee crepitus, and knee osteoarthritis confirmed by x-ray within 12 months. The protocol-specified outcomes were change from baseline through month 12 in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score, incidence of worsening knee osteoarthritis, and treatment-emergent adverse events (TEAEs) with romosozumab versus placebo. In a post hoc analysis, percentage change from baseline to month 12 in bone mineral density (BMD) was assessed. RESULTS: Of 7180 women in FRAME, 347 participated in the osteoarthritis substudy (placebo, 177; romosozumab, 170). At month 12, no significant difference in progression of knee osteoarthritis was observed with romosozumab versus placebo (least squares mean total WOMAC score: -2.2 vs. -1.3; P = 0.71). Incidence of worsening symptoms of knee osteoarthritis was comparable between romosozumab (17.1%) and placebo (20.5%) (odds ratio 0.9 [95% confidence interval: 0.5, 1.7]; P = 0.69). Incidence of TEAEs of osteoarthritis was numerically lower with romosozumab (13 [7.7%]) versus placebo (21 [12.0%]). BMD gains were higher with romosozumab. CONCLUSION: Romosozumab treatment did not impact knee pain or function in postmenopausal women with osteoporosis and knee osteoarthritis and resulted in significant BMD gains in these women.

Dual-energy X-ray Absorptiometry Trends Among US Medicare Beneficiaries: 2005-2019.

INTRODUCTION: Bone density measured using dual-energy X-ray absorptiometry (DXA) volume, performance site and interpreters have changed in the US since 2005. The purpose of this report is to provide updated trends in DXA counts, rates, place of service and interpreter specialty for the Medicare fee-for-service population. METHODS: The 100 % Medicare Physician/Supplier Procedure Summary Limited Data Set between 2005-2019 was used. DXA counts and annual rates per 10,000 Medicare beneficiaries were calculated. Annual distributions of scan performance location, provider type and interpreter specialty were described. Place of service trends (significance assigned at p < 0.05) of the mean annual share of DXA utilization were identified using linear regression. RESULTS: Annual DXA use per 10,000 beneficiaries peaked in 2008 at 832, declined to 656 in 2015 then increased (p < 0.001) by 38 per year to 807 in 2019. From 2005 to 2019 DXA performance in office settings declined from 70.7 % to 47.2 %. Concurrently, outpatient hospital (OH) DXA increased from 28.6 % to 51.7 %. In 2005, 43.5 % of DXAs were interpreted by radiologists. This increased (p < 0.001) in the office and OH, averaging 0.3 and 2.0 percentage points per year respectively, reaching 73.5 % in 2019. Interpretation by most non-radiologist specialties declined (p < 0.001). CONCLUSIONS: From 2005-2019, total DXA use among Medicare beneficiaries declined reaching a nadir in 2015 then returned to 2005 levels by 2019. Office DXA declined since 2005 with 51.7 % of all scans now occurring in an OH setting. The proportion of DXAs interpreted by radiologists increased over time, reaching 73.5 % in 2019.

Actualisation 2023 des lignes directrices de pratique clinique pour la prise en charge de l'ostéoporose et la prévention des fractures au Canada.

CONTEXTE: Au Canada, plus de 2 millions de personnes vivent avec l'ostéoporose, une maladie qui accroît le risque de fracture, ce qui fait augmenter la morbidité et la mortalité, et entraîne une perte de qualité de vie et d'autonomie. La présente actualisation des lignes directrices vise à accompagner les professionnelles et professionnels de la santé au Canada dans la prestation de soins visant à optimiser la santé osseuse et à prévenir les fractures chez les femmes ménopausées et les hommes de 50 ans et plus. MÉTHODES: Le présent document fournit une actualisation des lignes directrices de pratique clinique de 2010 d'Ostéoporose Canada sur le diagnostic et la prise en charge de l'ostéoporose au pays. Nous avons utilisé l'approche GRADE (Grading of Recommendations Assessment, Development and Evaluation) et effectué l'assurance de la qualité conformément aux normes de qualité et de présentation des rapports de la grille AGREE II (Appraisal of Guidelines for Research & Evaluation). Les médecins de premier recours et les patientes et patients partenaires ont été représentés à tous les niveaux des comités et des groupes ayant participé à l'élaboration des lignes directrices, et ont participé à toutes les étapes du processus pour garantir la pertinence des informations pour les futurs utilisateurs et utilisatrices. Le processus de gestion des intérêts concurrents a été entamé avant l'élaboration des lignes directrices et s'est poursuivi sur toute sa durée, selon les principes du Réseau international en matière de lignes directrices. Dans la formulation des recommandations, nous avons tenu compte des avantages et des risques, des valeurs et préférences de la patientèle, des ressources, de l'équité, de l'acceptabilité et de la faisabilité; la force de chacune des recommandations a été déterminée en fonction du cadre GRADE. RECOMMANDATIONS: Les 25 recommandations et les 10 énoncés de bonne pratique sont répartis en sections : activité physique, alimentation, évaluation du risque de fracture, instauration du traitement, interventions pharmacologiques, durée et séquence du traitement, et monitorage. La prise en charge de l'ostéoporose devrait se fonder sur le risque de fracture, établi au moyen d'une évaluation clinique réalisée avec un outil d'évaluation du risque de fracture validé. L'activité physique, l'alimentation et la pharmacothérapie sont des éléments essentiels à la stratégie de prévention des fractures, qui devraient être personnalisés. INTERPRÉTATION: Les présentes lignes directrices ont pour but d'outiller les professionnelles et professionnels de la santé et la patientèle afin qu'ensemble ils puissent parler de l'importance de la santé osseuse et du risque de fracture tout au long de la vie adulte avancée. La détection et la prise en charge efficace de la fragilité osseuse peuvent contribuer à réduire les fractures et à préserver la mobilité, l'autonomie et la qualité de vie.

CT image-based biomarkers acquired by AI-based algorithms for the opportunistic prediction of falls.

Objective: Evaluate whether biomarkers measured by automated artificial intelligence (AI)-based algorithms are suggestive of future fall risk. Methods: In this retrospective age- and sex-matched case-control study, 9029 total patients underwent initial abdominal CT for a variety of indications over a 20-year interval at one institution. 3535 case patients (mean age at initial CT, 66.5 ± 9.6 years; 63.4% female) who went on to fall (mean interval to fall, 6.5 years) and 5494 controls (mean age at initial CT, 66.7 ± 9.8 years; 63.4% females; mean follow-up interval, 6.6 years) were included. Falls were identified by electronic health record review. Validated and fully automated quantitative CT algorithms for skeletal muscle, adipose tissue, and trabecular bone attenuation at the level of L1 were applied to all scans. Uni- and multivariate assessment included hazard ratios (HRs) and area under the receiver operating characteristic (AUROC) curve. Results: Fall HRs (with 95% CI) for low muscle Hounsfield unit, high total adipose area, and low bone Hounsfield unit were 1.82 (1.65-2.00), 1.31 (1.19-1.44) and 1.91 (1.74-2.11), respectively, and the 10-year AUROC values for predicting falls were 0.619, 0.556, and 0.639, respectively. Combining all these CT biomarkers further improved the predictive value, including 10-year AUROC of 0.657. Conclusion: Automated abdominal CT-based opportunistic measures of muscle, fat, and bone offer a novel approach to risk stratification for future falls, potentially by identifying patients with osteosarcopenic obesity. Advances in knowledge: There are few well-established clinical tools to predict falls. We use novel AI-based body composition algorithms to leverage incidental CT data to help determine a patient's future fall risk.

Clinical practice guideline for management of osteoporosis and fracture prevention in Canada: 2023 update.

BACKGROUND: In Canada, more than 2 million people live with osteoporosis, a disease that increases the risk for fractures, which result in excess mortality and morbidity, decreased quality of life and loss of autonomy. This guideline update is intended to assist Canadian health care professionals in the delivery of care to optimize skeletal health and prevent fractures in postmenopausal females and in males aged 50 years and older. METHODS: This guideline is an update of the 2010 Osteoporosis Canada clinical practice guideline on the diagnosis and management of osteoporosis in Canada. We followed the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework and quality assurance as per Appraisal of Guidelines for Research and Evaluation (AGREE II) quality and reporting standards. Primary care physicians and patient partners were represented at all levels of the guideline committees and groups, and participated throughout the entire process to ensure relevance to target users. The process for managing competing interests was developed before and continued throughout the guideline development, informed by the Guideline International Network principles. We considered benefits and harms, patient values and preferences, resources, equity, acceptability and feasibility when developing recommendations; the strength of each recommendation was assigned according to the GRADE framework. RECOMMENDATIONS: The 25 recommendations and 10 good practice statements are grouped under the sections of exercise, nutrition, fracture risk assessment and treatment initiation, pharmacologic interventions, duration and sequence of therapy, and monitoring. The management of osteoporosis should be guided by the patient's risk of fracture, based on clinical assessment and using a validated fracture risk assessment tool. Exercise, nutrition and pharmacotherapy are key elements of the management strategy for fracture prevention and should be individualized. INTERPRETATION: The aim of this guideline is to empower health care professionals and patients to have meaningful discussions on the importance of skeletal health and fracture risk throughout older adulthood. Identification and appropriate management of skeletal fragility can reduce fractures, and preserve mobility, autonomy and quality of life.

Effects of Severe Lumbar Spine Structural Artifact on Trabecular Bone Score (TBS): The Manitoba BMD Registry.

Trabecular bone score (TBS) is a bone mineral density (BMD)-independent risk factor for fracture. During DXA analysis and BMD reporting, it is standard practice to exclude lumbar vertebral levels affected by structural artifact. Although TBS is relatively insensitive to degenerative artifact, it is uncertain whether TBS is still useful in the presence extreme structural artifact that precludes reliable spine BMD measurement even after vertebral exclusions. Among individuals aged 40 years and older undergoing baseline DXA assessment from September 2012 to March 2018 we identified three mutually exclusive groups: spine BMD reporting performed without exclusions (Group 1, N=12,865), spine BMD reporting performed with vertebral exclusions (Group 2, N=4867), and spine BMD reporting not performed due to severe structural artifact (Group 3, N=1541). No significant TBS difference was seen for Group 2 versus Group 1 (referent), whereas TBS was significantly greater in Group 3 (+0.041 partially adjusted, +0.043 fully adjusted). When analyzed by the reason for vertebral exclusion, multilevel degenerative changes significantly increased TBS (+0.041 partially adjusted, +0.042 fully adjusted), while instrumentation significantly reduced TBS (-0.059 partially adjusted, -0.051 fully adjusted). Similar results were seen when analyses were restricted to those in Group 3 with a single reason for vertebral exclusions, and when follow up scans were also included. During mean follow-up of 2.5 years there were 802 (4.2 %) individuals with one or more incident fractures. L1-L4 TBS showed significant fracture risk stratification in all groups including Group 3 (P-interaction >0.4). In conclusion, lumbar spine TBS can be reliably measured in the majority of lumbar spine DXA scans, including those with artifact affecting up to two vertebral levels. However, TBS is significantly affected by the presence of extreme structural artifact in the lumbar spine, especially those with multilevel degenerative disc changes and/or instrumentation that precludes reliable BMD reporting.

FRAX® Adjustment Using Renormalized Trabecular Bone Score (TBS) from L1 Alone may be Optimal for Fracture Prediction: The Manitoba BMD Registry.

Lumbar spine trabecular bone score (TBS) used in conjunction with FRAX® improves 10-year fracture prediction. The derived FRAX risk adjustment is based upon TBS measured from L1-L4, designated TBSL1-L4-FRAX. In prior studies, TBS measurements that include L1 and exclude L4 give better fracture stratification than L1-L4. We compared risk stratification from TBS-adjusted FRAX using TBS derived from different combinations of upper lumbar vertebral levels renormalized for level-specific differences in individuals from the Manitoba Bone Density Program aged >40 years with baseline assessment of TBS and FRAX. TBS measurements for L1-L3, L1-L2 and L1 alone were calculated after renormalization for level-specific differences. Corresponding TBS-adjusted FRAX scores designated TBSL1-L3-FRAX, TBSL1-L2-FRAX and TBSL1-FRAX were compared with TBSL1-L4-FRAX for fracture risk stratification. Incident major osteoporotic fractures (MOF) and hip fractures were assessed. The primary outcome was incremental change in area under the curve (ΔAUC). The study population included 71,209 individuals (mean age 64 years, 89.8% female). Before renormalization, mean TBS for L1-3, L1-L2 and L1 was significantly lower and TBS-adjusted FRAX significantly higher than from using TBSL1-L4. These differences were largely eliminated when TBS was renormalized for level-specific differences. During mean follow-up of 8.7 years 6745 individuals sustained incident MOF and 2039 sustained incident hip fractures. Compared with TBSL1-L4-FRAX, use of FRAX without TBS was associated with lower stratification (ΔAUC = -0.009, p < 0.001). There was progressive improvement in MOF stratification using TBSL1-L3-FRAX (ΔAUC = +0.001, p < 0.001), TBSL1-L2-FRAX (ΔAUC = +0.004, p < 0.001) and TBSL1-FRAX (ΔAUC = +0.005, p < 0.001). TBSL1-FRAX was significantly better than all other combinations for MOF prediction (p < 0.001). Incremental improvement in AUC for hip fracture prediction showed a similar but smaller trend. In conclusion, this single large cohort study found that TBS-adjusted FRAX performance for fracture prediction was improved when limited to the upper lumbar vertebral levels and was best using L1 alone.

Adjusting Trabecular Bone Score (TBS) for Level-Specific Differences Reduces FRAX®-Based Treatment Reclassification in Patients with Vertebral Exclusions: The Manitoba BMD Registry.

Trabecular bone score (TBS) is a FRAX®-independent risk factor for fracture prediction. TBS values increase from cranial to caudal, with the following mean differences between TBSL1-L4 and individual lumbar vertebrae: L1 -0.093, L2 -0.008, L3 +0.055 and L4 +0.046. Excluding vertebral levels can affect FRAX-based treatment recommendations close to the intervention threshold. We examined the effect of adjusting for level-specific TBS differences in individuals with vertebral exclusions due to structural artifact on TBS-adjusted FRAX-based treatment recommendations. We identified 71,209 individuals aged ≥40 years with TBS and FRAX calculations through the Manitoba Bone Density Program. In the 24,428 individuals with vertebral exclusions, adjusting TBS using these level-specific factors agreed with TBSL1-L4 (mean difference -0.001). We compared FRAX-based treatment recommendations for TBSL1-L4 and for non-excluded vertebral levels before and after adjusting for level-specific TBS differences. Among those with baseline major osteoporotic fracture risk ≥15 %, TBS with vertebral exclusions reclassified FRAX-based treatment in 10.6 % of individuals compared with TBSL1-L4, and was reduced to 7.2 % after adjusting for level-specific differences. In 11,131 patients where L1-L2 was used for BMD reporting (the most common exclusion pattern with the largest TBS effect), treatment reclassification was reduced from 13.9 % to 2.4 %, respectively. Among individuals with baseline hip fracture risk ≥2 %, TBS vertebral exclusions reclassified 7.1 % compared with TBSL1-L4, but only 4.5 % after adjusting for level-specific differences. When L1-L2 was used for BMD reporting, treatment reclassification from hip fracture risk was reduced from 9.2 % to 5.2 %. In conclusion, TBS and TBS-adjusted FRAX-based treatment recommendations are affected by vertebral level exclusions for structural artifact. Adjusting for level-specific differences in TBS reduces reclassification in FRAX-based treatment recommendations.

Effect of BMI-Discordant Abdominal Tissue Thickness on Fracture Probability: A Registry-Based Study.

FRAX, which is used to assess fracture probability, considers body mass index (BMI), but BMI may not reflect individual variation in body composition and distribution. We examined the effect of BMI-discordant abdominal thickness on FRAX-derived fracture probability for major osteoporotic fracture (MOF) and hip fracture. We studied 73,105 individuals, mean age 64.2 years. During mean 8.7 years, 7048 (9.6%) individuals sustained incident MOF, including 2155 (3.0%) hip fractures. We defined abdominal thickness index (ATI) as the difference between abdominal thickness measured by dual-energy X-ray absorptiometry (DXA) and thickness predicted by BMI using sex-stratified regression. ATI was categorized from lower (<-2 cm, -2 to -1 cm) to higher (1-2 cm, >+2 cm) with referent around zero (-1 to +1 cm). Adjusted for FRAX probability, increasing ATI was associated with incident MOF and hip fracture (p < 0.001). For the highest ATI category, MOF risk was increased (hazard ratio [HR] = 1.23, 95% confidence interval [CI] 1.12-1.35) independent of FRAX probability. Similar findings were noted for hip fracture probability (HR = 1.28, 95% CI 1.09-1.51). There was significant age-interaction with much larger effects before age 65 years (HR = 1.44, 95% CI 1.23-1.69 for MOF; 2.29, 95% CI 1.65-3.18 for hip fracture). In contrast, for the subset of individuals with diabetes, there was also increased risk for those in the lowest ATI category (HR = 1.73, 95% CI 1.12-2.65 for MOF; 2.81, 95% CI 1.59-4.97 for hip fracture). Calibration plots across ATI categories demonstrated deviation from the line of identity in women (calibration slope 2.26 for MOF, 2.83 for hip fracture). An effect of ATI was not found in men, but this was inconclusive as the sex-interaction terms did not show significant effect modification. In conclusion, these data support the need to investigate increased abdominal thickness beyond that predicted by BMI and sex as a FRAX-independent risk factor for fracture. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Vitamin D status and supplementation before and after Bariatric Surgery: Recommendations based on a systematic review and meta-analysis.

Bariatric surgery is associated with a postoperative reduction of 25(OH) vitamin D levels (25(OH)D) and with skeletal complications. Currently, guidelines for 25(OH)D assessment and vitamin D supplementation in bariatric patients, pre- and post-surgery, are still lacking. The aim of this work is to analyse systematically the published experience on 25(OH)D status and vitamin D supplementation, pre- and post-surgery, and to propose, on this basis, recommendations for management. Preoperatively, 18 studies including 2,869 patients were evaluated. Prevalence of vitamin D insufficiency as defined by 25(OH)D < 30 ng/mL (75 nmol/L) was 85%, whereas when defined by 25(OH)D < 20 ng/mL (50 nmol/L) was 57%. The median preoperative 25(OH)D level was 19.75 ng/mL. After surgery, 39 studies including 5,296 patients were analysed and among those undergoing either malabsorptive or restrictive procedures, a lower rate of vitamin D insufficiency and higher 25(OH)D levels postoperatively were observed in patients treated with high-dose oral vitamin D supplementation, defined as ≥ 2,000 IU/daily (mostly D3-formulation), compared with low-doses (< 2,000 IU/daily). Our recommendations based on this systematic review and meta-analysis should help clinical practice in the assessment and management of vitamin D status before and after bariatric surgery. Assessment of vitamin D should be performed pre- and postoperatively in all patients undergoing bariatric surgery. Regardless of the type of procedure, high-dose supplementation is recommended in patients after bariatric surgery.

MRI-based vertebral bone quality score: relationship with age and reproducibility.

Vertebral bone quality (VBQ) score is an opportunistic measure of bone mineral density using routine preoperative MRI in spine surgery. VBQ score positively correlates with age and is reproducible across serial scans. However, extrinsic factors, including MRI machine and protocol, affect the VBQ score and must be standardized. PURPOSE: The purposes of this study were to determine whether VBQ score increased with age and whether VBQ remained consistent across serial MRI studies obtained within 3 months. METHODS: This retrospective study evaluated 136 patients, age 20-69, who received two T1-weighted lumbar MRI within 3 months of each other between January 2011 and December 2021. VBQ(L1-4) score was calculated as the quotient of L1-L4 signal intensity (SI) and L3 cerebral spinal fluid (CSF) SI. VBQ(L1) score was calculated as the quotient of L1 SI and L1 CSF SI. Regression analysis was performed to determine correlation of VBQ(L1-4) score with age. Coefficient of variation (CV) was used to determine reproducibility between VBQ(L1-4) scores from serial MRI scans. RESULTS: One hundred thirty-six patients (mean ± SD age 44.9 ± 12.5 years; 53.7% female) were included in this study. Extrinsic factors affecting the VBQ score included patient age, MRI relaxation time, and specific MRI machine. When controlling for MRI relaxation/echo time, the VBQ(L1-4) score was positively correlated with age and had excellent reproducibility in serial MRI with CV of 0.169. There was excellent agreement (ICC > 0.9) of VBQ scores derived from the two formulas, VBQ(L1) and VBQ(L1-4). CONCLUSION: Extrinsic factors, including MRI technical factors and age, can impact the VBQ(L1-4) score and must be considered when using this tool to estimate bone mineral density (BMD). VBQ(L1-4) score was positively correlated with age. Reproducibility of the VBQ(L1-4) score across serial MRI is excellent especially when controlling for technical factors, supporting use of the VBQ score in estimating BMD. The VBQ(L1) score was a reliable alternative to the VBQ(L1-4) score.

Efficacy and Safety of Transdermal Abaloparatide in Postmenopausal Women with Osteoporosis: A Randomized Study.

Anabolic therapies, recommended for patients at very high fracture risk, are administered subcutaneously (SC). The objective of this study was to evaluate the efficacy and safety of the abaloparatide microstructured transdermal system (abaloparatide-sMTS) as an alternative to the SC formulation. This phase 3, noninferiority study (NCT04064411) randomly assigned postmenopausal women with osteoporosis (N = 511) 1:1 to open-label abaloparatide administered daily via abaloparatide-sMTS or SC injection for 12 months. The primary comparison between treatment groups was the percentage change in lumbar spine bone mineral density (BMD) at 12 months, with a noninferiority margin of 2.0%. Secondary endpoints included percentage change in total hip and femoral neck BMD, bone turnover markers, dermatologic safety, and new clinical fracture incidence. At 12 months, percentage increase from baseline in lumbar spine BMD was 7.14% (SE: 0.46%) for abaloparatide-sMTS and 10.86% (SE: 0.48%) for abaloparatide-SC (treatment difference: -3.72% [95% confidence interval: -5.01%, -2.43%]). Percentage change in total hip BMD was 1.97% for abaloparatide-sMTS and 3.70% for abaloparatide-SC. Median changes from baseline at 12 months in serum procollagen type I N-terminal propeptide (s-PINP) were 52.6% for abaloparatide-sMTS and 74.5% for abaloparatide-SC. Administration site reactions were the most frequently reported adverse events (abaloparatide-sMTS, 94.4%; abaloparatide-SC, 70.5%). Incidence of serious adverse events was similar between groups. Mild or moderate skin reactions occurred with abaloparatide-sMTS with no identifiable risk factors for sensitization reactions. Few new clinical fractures occurred in either group. Noninferiority of abaloparatide-sMTS to abaloparatide-SC for percentage change in spine BMD at 12 months was not demonstrated; however, clinically meaningful increases from baseline in lumbar spine and total hip BMD were observed in both treatment groups. © 2023 Radius Health, Inc and The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Urinary 2- to 16α-hydroxyestrone ratio did not change with cruciferous vegetable intake in premenopausal women.

The mass ratio of urinary 2-hydroxyestrone to 16-α-hydroxyestrone (2:16) is hypothesized as a biomarker of breast cancer risk in premenopausal women, with higher ratios being theoretically protective. Cruciferous vegetable intake has been associated with higher urinary 2:16 in some studies. We investigated whether a whole-food supplement made from dried Brussels sprouts and kale would increase urinary 2:16 in comparison with placebo or cruciferous vegetables in women. This randomized, parallel arm, placebo-controlled, partly blinded study included 78 healthy premenopausal women (38-50 y) with screening urinary 2:16 ≤3.0. Subjects received either six capsules containing 550 mg dried Brussels sprouts and kale per capsule, 40 g daily alternating broccoli or Brussels sprouts, or placebo for eight weeks. Urinary 2:16 and creatinine were measured at baseline, four, and eight weeks. Intent-to-treat repeated measures-ANOVA with multiple imputation (n=100) for missing values identified no treatment effect (P=0.9) or treatment-by-time interaction (P=0.6); however, a significant time effect was noted (P=0.02). Per-protocol analyses including complete cases found no treatment effect (P=1) or treatment-by-time interaction (P=0.6); however, the significant time effect remained (P=0.03). Restricting analysis to subjects with >80% compliance maintained the time effect (P=0.02). Using Pearson correlations, android-pattern and android:gynoid fat were predictive of change (P≤0.05). In conclusion, neither cruciferous supplements nor an added vegetable serving altered urinary 2:16 in premenopausal women with eight weeks treatment. This ratio did vary with time, which is important for designing future trials.

Advances in Osteoporosis Therapy: Focus on Osteoanabolic Agents, Secondary Fracture Prevention, and Perioperative Bone Health.

PURPOSE OF REVIEW: This review summarizes recently published data and other developments around osteoanabolic osteoporosis therapies in patients with very high fracture risk, including those undergoing bone-related surgery. RECENT FINDINGS: Two osteoanabolic agents, abaloparatide and romosozumab, were recently approved for treatment of patients with osteoporosis at high fracture risk. These agents, along with teriparatide, are valuable for primary and secondary fracture prevention. Orthopedic surgeons are well positioned to facilitate secondary fracture prevention via referrals to fracture liaison services or other bone health specialist colleagues. This review aims to help surgeons understand how to identify patients with sufficiently high fracture risk to warrant consideration of osteoanabolic therapy. Recent evidence around the perioperative use and potential benefits of osteoanabolic agents in fracture healing and other orthopedic settings (e.g., spinal fusion and arthroplasty) in individuals with osteoporosis is also discussed. Osteoanabolic agents should be considered for patients with osteoporosis at very high fracture risk, including those with prior osteoporotic fractures and those with poor bone health who are undergoing bone-related surgery.