Concentrations of total, bioavailable, and free 25OHD in individuals with and without primary hyperparathyroidism and their correlations to DXA and trabecular bone score

ABSTRACT Objective: This study aimed to investigate the association between 25OHD (total, bioavailable and free) with bone mass and microarchitecture among primary hyperparathyroidism (PHPT) patients and controls. Subjects and methods: Sixty-four patients in the preoperative period of PHPT and 63 matched controls, who had not taken vitamin D in the last three months. To calculate the bioavailable and free 25OHD, the genetic variants of the vitamin D-binding protein (DBP) were determined. Bone mineral density (BMD) was determined by dual-energy X-ray absorptiometry (DXA). The distributions of total, bioavailable and free 25OHD and their correlation with TBS and DXA were evaluated. Results: PHPT showed BMD and TBS values lower than CTRL in all locations (p < 0.05). There were no statistical differences in the levels of free, bioavailable and total 25OHD between the PHPT and CTRL groups [mean, min-max: 3.4 (1.4-8.6) vs. 3.1 (1.0-9.8) pg/mL, 1.51 (0.43-3.58) vs. 1.41 (0.38-3.48) ng/mL, 22.6 (11.0-39.9) vs. 20.6 (8.9-35.3) ng/dL, respectively; (p > 0.05). The distribution of DBP haplotypes was similar between groups. DXA showed no correlation with any form of 25OHD in both groups. TBS presented a weak correlation with the total 25OHD in PHPT (r = 0.28; p = 0.02) and a moderate correlation with the total, free and bioavailable 25OHD in CTRL (r = 0.42; r = 0.42; r = 0.43; respectively, p < 0.01). Conclusion: The concentrations of total, free and bioavailable 25OHD were similar in both the PHPT and control groups. 25OHD concentrations correlated positively with TBS and not with DXA, especially in controls, suggesting that this method may be more sensitive to assessing the consequences of vitamin D deficiency on bone quality in individuals without PHPT.

Update on trabecular bone score

ABSTRACT Trabecular bone score (TBS) is an indirect and noninvasive measure of bone quality. A low TBS indicates degraded bone microarchitecture, predicts osteoporotic fracture, and is partially independent of clinical risk factors and bone mineral density (BMD). There is substantial evidence supporting the use of TBS to assess vertebral, hip, and major osteoporotic fracture risk in postmenopausal women, as well as to assess hip and major osteoporotic fracture risk in men aged > 50 years. TBS complements BMD information and can be used to adjust the FRAX (Fracture Risk Assessment) score to improve risk stratification. While TBS should not be used to monitor antiresorptive therapy, it may be potentially useful for monitoring anabolic therapy. There is also a growing body of evidence indicating that TBS is particularly useful as an adjunct to BMD for fracture risk assessment in conditions associated with increased fracture risk, such as type-2 diabetes, chronic corticosteroid excess, and other conditions wherein BMD readings are often misleading. The interference of abdominal soft tissue thickness (STT) on TBS should also be considered when interpreting these findings because image noise can impact TBS evaluation. A new TBS software version based on an algorithm that accounts for STT rather than BMI seems to correct this technical limitation and is under development. In this paper, we review the current state of TBS, its technical aspects, and its evolving role in the assessment and management of several clinical conditions.

Utilidad del Trabecular Bone Score combinado con la densitometría ósea en la valoración de una serie 194 pacientes / Usefulness of Trabecular Bone Score in combination with bone densitometry to assess a series of 194 patients / Utilidade do Trabecular Bone Score combinado com densitometria óssea na avaliação de uma série de 194 pacientes

Resumen: Introducción: la mayoría de las fracturas por fragilidad ocurren en rango densitométrico de osteopenia, la escala ósea trabecular (TBS) permite valorar aspectos de la microarquitectura que influyen en la resistencia ósea. Objetivo: describir las características clínicas y los hallazgos de la microarquitectura ósea aplicando TBS combinado con densitometría ósea (DXA) en un grupo de pacientes. Material y métodos: estudio descriptivo, de recolección retrospectiva. Se incluyen los pacientes a los que se les realizó DXA con TBS en el INRU en julio y agosto de 2020. Resultados: se analizaron 194 pacientes, 173 (89%) de sexo femenino y 21 (11%) de sexo masculino. El 36,1% (70 pacientes) en rango de osteopenia, 36,1 (70 pacientes) en rango de osteoporosis. El 32,9% (23 pacientes) con osteopenia y el 47,1% (33 pacientes) con osteoporosis tenían microarquitectura degradada. 76,9% de los pacientes con artritis reumatoidea y 45,8% de los que tenían espondiloartritis presentaban microarquitectura alterada. Conclusiones: el TBS permitió reestratificar el riesgo de fractura en un número importante de pacientes, mostrándose como una herramienta muy útil en la valoración complementaria de la salud ósea.

Summary: Introduction: most fractures that result from bone fragility occur in the osteopenia range The trabecular bone score (TBS) enables the assessment of microarchitecture aspects that impact bone resistance. Objective: to describe the clinical characteristics and findings of bone microarchitecture, by applying TBS and bone densitometry in a group of patients. Method: descriptive study of retrospective collection. Patients who were included in the study underwent a Dual-energy X-ray Absorptiometry (DXA) with TBS at the National Rheumatology Service between July and August, 2020. Results: 94 patients were analysed, 173 (89%) were female and 21 (11%) were male. 36.1% (70 patients) lay in the osteopenia range, 36.1 (70 patients) in the osteoporotic range. 32.9% (23 patients) with osteopenia and 47.1% (33 patients) with osteoporosis evidenced a degraded bone microarchitecture. 76.9 % of patients with rheumatoid arthritis and 45.8 % of patients with spondyloarthritis respectively evidenced altered bone microarchitecture. Conclusions: TBS allowed stratification of fracture risk in a significant number of patients, which may suggest it is a useful tool for complementary assessment of bone health.

Resumo: Introdução: a maioria das fraturas por fragilidade ocorre na faixa densitométrica da osteopenia; o escore de osso trabecular (TBS) permite avaliar aspectos da microarquitetura que influenciam a resistência óssea. Objetivo: descrever as características clínicas e os achados da microarquitetura óssea aplicando TBS combinado com densitometria óssea (DMO) em um grupo de pacientes. Material e métodos: estudo descritivo, retrospectivo, incluindo pacientes que realizaram DXA (absorciometria de raios-X de dupla energia) com TBS no INRU em julho e agosto de 2020. Resultados: foram analisados 194 pacientes, 173 (89%) mulheres e 21 (11%) homens. 36,1% (70 pacientes) na faixa de osteopenia, 36,1 (70 pacientes) na faixa de osteoporose. 32,9% (23 pacientes) com osteopenia e 47,1% (33 pacientes) com osteoporose tinham microarquitetura degradada. Nos pacientes com artrite reumatoide 76,9% e nas espondiloartrite 45,8% apresentaram microarquitetura alterada, respectivamente. Conclusões: a TBS permitiu fazer uma nova estratificação do risco de fratura em um número significativo de pacientes, mostrando-se uma ferramenta muito útil na avaliação complementar da saúde óssea.

Trabecular Bone Score Is More Sensitive to Asthma Severity and Glucocorticoid Treatment Than Bone Mineral Density in Asthmatics

PURPOSE: In asthmatic patients, treatment with corticosteroids, in addition to conventional risk factors for osteoporosis, may lead to bone loss. Trabecular bone score (TBS) is an indirect new parameter of bone quality. This study aimed to evaluate TBS in asthmatics in comparison to propensity score-matched controls and to investigate correlations between TBS and cumulative systemic and inhaled corticosteroid doses 1 year prior to bone mineral density (BMD) measurement in patients with asthma. METHODS: In total, 627 patients with asthma and the same number of non-asthmatic controls matched for sex and age were included in this retrospective cohort study. TBS was calculated in the lumbar region, based on 2 dimensional projections of dual-energy X-ray absorptiometry. RESULTS: Patients with severe asthma exhibited lower vertebral TBS values (1.32 ± 0.1) than those with non-severe asthma (1.36 ± 0.1, P = 0.001), with non-active asthma (1.38 ± 0.1, P < 0.001), and without asthma (1.39 ± 0.1, P < 0.001). No significant differences in BMD were noted among the study groups. TBS was significantly correlated with cumulative systemic and inhaled corticosteroid doses as well as asthma duration, lung function and airway hyper-responsiveness. A generalized linear model revealed that age, severe asthma, and frequency of oral corticosteroid burst were significant predictors for TBS levels. CONCLUSIONS: TBS can be used as an early indicator of altered bone quality stemming from glucocorticoid therapy or, possibly, more severe asthma.

Clinical significance of trabecular bone score for prediction of pathologic fracture risk in patients with multiple myeloma

OBJECTIVES: Osteolytic bone lesions are common complications in multiple myeloma (MM), and can have an impact on quality of life due to the risk of fractures. Trabecular bone score (TBS) is a novel texture index derived from dual energy x-ray absorptiometry (DXA) of lumbar spine (LS) images that provides information about bone microarchitecture. The aim of this study was to evaluate whether TBS is useful in predicting bone fractures in MM patients. METHODS: TBS was calculated retrospectively from existing DXA images of the LS, in 20 patients with newly diagnosed MM. We analyzed the development of fractures in these patients. RESULTS: The median age of the patients was 66 years (range, 49–77 years). Osteolytic bone lesions were observed in 18 patients (90%) at the time of diagnosis. The median duration of follow-up was 40.0 months (95% confidence interval [CI], 33.2–46.2), 6 fracture events (long-bone fractures in 5 events, vertebral fracture in 1) occurred in 5 patients (25%). There were no significant differences between patients who experienced new onset fractures and patients who did not for all TBSs and T-scores, although the fracture group had lower levels than the no fracture group. However, among TBSs of individual LSs, only L2 showed significantly lower scores in patients who developed fractures (1.135 ± 0.085 [95% CI, 1.030–1.241] vs. 1.243 ± 0.169 [95% CI, 1.149–1.336], P = 0.032). CONCLUSIONS: TBS of the LS in MM patients may be helpful in predicting development of fractures; however, further investigation is needed.

Evaluación de score de hueso trabecular (TBS) en pacientes menopáusicas con fracturas y sin ellas / Trabecular bone score evaluation in postmenopausal women with or without fractures

El score de hueso trabecular (TBS, Trabecular Bone Score) es una medición de la textura de los grises derivada de la evaluación del raquis por DXA y proporciona un índice de la microarquitectura ósea. Se ha demostrado que los valores bajos presentan capacidad para predecir fracturas. Nuestro objetivo fue evaluar si existían diferencias entre los valores de TBS de pacientes con fracturas frente a no fracturadas. Materiales y métodos: se revisaron 159 historias clínicas de mujeres menopáusicas que consultaron para evaluación de su salud ósea. Se consideraron los antecedentes autorreferidos de fracturas (Fx), la DMO de raquis, cuello femoral y fémur total y TBS. Resultados: treinta pacientes (18,9%) presentaron fracturas y en ellas se observó menor TBS (con Fx: 1,295±83 vs. sin Fx: 1,366±84, p<0,0001), menor índice de masa corporal (IMC) (con Fx: 23,7±1,9 vs. sin Fx: 25,7±4,2, p=0,02), sin diferencias en la edad (p=0,39), ni en valores de DMO (L1-L4 p=0,11, cuello femoral p=0,20 y fémur total p= 0,12). Muchas de las fracturas ocurrieron en pacientes sin osteoporosis por DXA. Conclusiones: el TBS aumentaría la capacidad de DXA para identificar a mujeres argentinas en riesgo de padecer fracturas sin tener osteoporosis densitométrica. Este es el primer trabajo realizado en la Argentina con medición de TBS. (AU)

Trabecular Bone Score (TBS) is a measure of the grey scale derived from DXA lumbar image and provides information about microarchitecture. It has been shown that low TBS values can predict fractures. Our objective was to evaluate if there are any differences between the TBS values in patients with fractures vs. non-fractures. Materials and methods: We reviewed 159 medical records of menopausal women who consulted for evaluation of their bone health. Self-reported fractures (Fx), spine BMD, femoral neck and total femur and TBS were evaluated. Results: thirty patients (18.9%) presented fractures and they showed lower TBS (with Fx: 1,295±0,083 vs. without Fx: 1,366±0,084, p<0.0001), lower body mass index (BMI) (with Fx: 23.7±1.9 vs. without Fx 25.7±4.2, p=0.02), without differences in ages (p=0.39) or in BMD values (L1-L4 p=0.11, femoral neck p=0.20 and total femur p=0.12). Some fractures occurred in patients without osteoporosis, as determined by DXA. Conclusions: TBS would increase the ability of DXA to identify Argentine women at risk for fractures without densitometric osteoporosis. This is the first work done in Argentina with TBS measurement. (AU)

The correlation between bone mineral density/trabecular bone score and body mass index, height, and weight

OBJECTIVES: This study investigated the correlation between bone mineral density (BMD)/trabecular bone score (TBS) and body mass index (BMI), height and weight in Korean adults. METHODS: We enrolled 2555 female participants in their 20s–80s and 1631 male participants in their 20s–70s. Participants with history of previous vertebral surgeries or current vertebral diseases were excluded. Female and male participants were divided into osteoporosis group (n = 136 and n = 31, respectively), osteopenia group (n = 822 and n = 460, respectively), and normal group (n = 1596 and n = 1140, respectively) based on their BMD T-score. Dual-energy X-ray absorptiometry image analysis and linear regression analysis were conducted on each participant in each group to determine the P-value and the correlation between BMD T-score/TBS T-score and BMI, weight, and height. RESULTS: We found a significant correlation between BMI and TBS in both male and female participants. In the male participants, the correlation coefficient increased progressively from the normal group to the osteoporosis group. In the female group, we observed a significant positive correlation between height and TBS, and in the male group a significant negative correlation between weight and TBS was observed. CONCLUSIONS: BMI and weight are closely correlated to body fat content. BMD was positively correlated to BMI and weight, while TBS was negatively correlated to BMI and weight. Therefore, although BMI causes an increase in BMD, it appears to be negatively affecting bone quality.

Effects of statin on trabecular bone microstructure in middle and aged people / 天津医药

Objective To investigate the effect of statin on trabecular bone microstructure by using trabecular bone score (TBS), a new type of bone microstructure evaluation index. Methods A total of 253 middle and aged patients hospitalized in the First Affiliated Hospital of Nanjing Medical University between January 2014 and March 2016 were retrospectively analyzed. According to whether statin was used or not, patients were divided into two groups: 90 patients in the statin use group (statin was use for more than 1 year) and 163 in the control group (not taken any statin). Serum biochemical indicators, such as triacylglycerol, total cholesterol, high density lipoprotein cholesterol, low density lipoprotein cholesterol, alkaline phosphatase, fasting blood glucose and 25 hydroxy vitamin D, were compared between the two groups. Dual energy X-ray absorptiometry (DXA) was used to measure the bone mineral density (BMD) of lumbar spine and femoral neck. TBS was calculated with TBS iNsight? software, and the DXA image of lumbar spine were analyzed. Results Values of total cholesterol and low density lipoprotein cholesterol were significantly lower in statin group compared with those of control group (P0.05). There was higher lumbar spine BMD statin group compared to that of control group (g/cm2:1.04 ± 0.19 vs. 0.96 ± 0.14, P0.05). Conclusion Statin increases lumbar spine BMD and improves trabecular bone microstructure in middle and aged people.

Type 2 diabetes mellitus and bone fragility: Special focus on bone imaging

Fragility fracture rate is increased in type 2 diabetes patients despite of higher bone mineral density than non-diabetes control subjects. Vertebral fractures are usually asymptomatic; therefore, morphometric radiologic evaluation should be considered especially for diabetes patients. Bone quality may more contribute to the increased risk of osteoporotic fractures in patients with type 2 diabetes than bone mass. Hip geometry, cortical porosity, and trabecular bone score have been studied as bone quality parameters by imaging in type 2 diabetes mellitus.

Changes in bone mineral density and trabecular bone score in Graves' disease patients after anti-thyroid therapy

OBJECTIVE: The purpose of this study was to evaluate changes in bone quantity based on bone mineral density (BMD) and bone quality based on trabecular bone score (TBS) in Graves' disease patients after anti-thyroid therapy. RESEARCH DESIGN AND METHOD: This retrospective study included premenopausal female and male patients with Graves' disease who received BMD measurement more than two times during treatment. BMD and thyroid function tests with free thyroxine (FT4), total triiodothyronine (T3), thyroid stimulating hormone (TSH), and TSH receptor antibody (TRAb) levels were collected two times during follow-up. TBS was calculated using TBS insight® software (version 2.1) from dual-energy X-ray absorptiometry images. RESULTS: Thirty Graves' disease patients (17 males, 56%; 13 premenopausal females, 44%) with a mean age of 35.3 ± 9.9 years were included. The mean follow-up period was 20.7 ± 8.5 months. The median levels of FT4, TSH and TRAb improved at follow-up [2.55 ng/dL (Interquartile range (IQR) 2.07-3.78) to 1.28 ng/dL (IQR 1.23-1.39), 0.015 mIU/L (IQR 0.01-0.04) to 0.89 mIU/L (IQR 0.35-1.55), 17.0 IU/L (IQR 5.0-40.3) to 5.0 IU/L (5.0-6.0), respectively; p < 0.001]. Median BMD (lumbar spine) values also improved from 1.118 g/cm² (IQR 1.000-1.119) to 1.167 g/cm² (IQR 1.050-1.219) ( p = 0.001) at follow-up. TBS increased from 1.377 (IQR 1.299-1.422) to 1.390 (IQR 1.327-1.430) after treatment ( p = 0.038). CONCLUSIONS: Both bone quality and density improved after anti-thyroid treatment in premenopausal female and male Graves' disease patients.

Dual-Energy X-Ray Absorptiometry: Beyond Bone Mineral Density Determination

Significant improvements in dual-energy X-ray absorptiometry (DXA) concerning quality, image resolution and image acquisition time have allowed the development of various functions. DXA can evaluate bone quality by indirect analysis of micro- and macro-architecture of the bone, which and improve the prediction of fracture risk. DXA can also detect existing fractures, such as vertebral fractures or atypical femur fractures, without additional radiologic imaging and radiation exposure. Moreover, it can assess the metabolic status by the measurement of body composition parameters like muscle mass and visceral fat. Although more studies are required to validate and clinically use these parameters, it is clear that DXA is not just for bone mineral densitometry.

Valor clínico del puntaje óseo trabecular calculado a partir de la absorciometría de rayos X de energía dual de columna / Clinical importance of the Trabecular Bone Score obtained from spine dual-energy x-ray absorptiometry

Intrínsecamente, se acepta el hecho de que definir a la osteoporosis solamente sobre la base de la densidad mineral ósea proyectada (DMO mediante DXA) ha llegado a su límite. De hecho, el aspecto multifactorial de esta enfermedad hace que la definición actual de osteoporosis evolucione hacia un modelo de riesgo complejo basado en el Factor de Riesgo Clínico (FRC) y la DMO. El puntaje óseo trabecular (TBS, Trabecular Bone Score) es una nueva medición de escala de grises que se basa en el uso de variogramas experimentales sobre imágenes en proyección 2D, y que permite diferenciar entre dos microarquitecturas tridimensionales (3D) que presentan la misma densidad ósea pero diferentes características trabeculares. El TBS mide la tasa promedio de variación local en escala de grises sobre imágenes de proyección 2D. Este parámetro se obtiene luego del re-análisis de un examen de DXA, y puede compararse con la DMO dado que ambos evalúan la misma región ósea. El valor agregado del TBS respecto de la densitometría mineral ósea para la evaluación del riesgo de fracturas ha sido documentado en estudios transversales, prospectivos y longitudinales. De hecho, se ha hallado que el TBS: 1) es más bajo en mujeres posmenopáusicas con una fractura osteoporótica previa, comparado con mujeres sin fractura pareadas por edad y DMO; 2) brinda un aumento incremental en el odds ratio para fractura de columna cuando se combina con la DMO de columna; 3) es más bajo en mujeres con fracturas (comparado con aquellas sin fracturas), independientemente de si su DMO reúne los criterios para osteoporosis u osteopenia; 4) predice fracturas en forma prospectiva, tal como lo hace la DMO; 5) rescata alrededor de 1/3 de las fracturas clasificadas de manera errónea según la definición de DMO de la OMS para osteoporosis aislada; y 6) se comporta de manera diferente de acuerdo con el tipo de terapia ósea implementada. El objetivo de esta breve revisión consiste en brindar información acerca de los ensayos clínicos actuales referentes al TBS, además de posicionar a este parámetro en la práctica clínica como complemento de la DMO en vista de su actual validación.

Intrinsically it is accepted that defining osteoporosis on the sole basis of projected bone mineral density (BMD by DXA) has reached its limit. Indeed, the multifactorial aspect of this disease means that the current definition of osteoporosis is evolving towards a complex risk model based on Clinical Risk Factor (CRF) and BMD. The Trabecular Bone Score (TBS) is a novel grey-level texture measurement that is based on the use of experimental variograms of 2D projection images, and is able to differentiate between two 3-dimensional (3D) micro-architectures that exhibit the same bone density, but different trabecular characteristics. TBS measures the mean rate of local variation of grey levels in 2D projection images. The TBS is obtained after re-analysis of a DXA exam, and can be compared with BMD, since both evaluate the same region of bone. The added value of the TBS in bone mineral densitometry for fracture risk assessment has been documented in cross-sectional, prospective and longitudinal studies. Indeed, TBS has been found to: 1) be lower in post-menopausal women with a past osteoporotic fracture compared with age- and BMD-matched women without fracture; 2) give an incremental increase in the odds ratio for spine fracture when combined with spine BMD; 3) be lower in women with (versus without) fractures, irrespective of whether their BMD met the criteria for osteoporosis or osteopenia; 4) prospectively predict facture as well as spine BMD; 5) recapture around 1/3 of mis-classified fractures according to the BMD WHO definition of osteoporosis alone, and 6) react differently according to the type of bone therapy. The aim of this short review is to report the current clinical studies as well as to position TBS in clinical routine to complement BMD in the light of its current validation.

Trabecular bone score: perspectives of an imaging technology coming of age / Escore de osso trabecular: perspectivas de um método de imagem em aprimoramento

The trabecular bone score (TBS) is a new method to describe skeletal microarchitecture from the dual energy X-ray absorptiometry (DXA) image of the lumbar spine. While TBS is not a direct physical measurement of trabecular microarchitecture, it correlates with micro-computed tomography (µCT) measures of bone volume fraction, connectivity density, trabecular number, and trabecular separation, and with vertebral mechanical behavior in ex vivo studies. In human subjects, TBS has been shown to be associated with trabecular microarchitecture and bone strength by high resolution peripheral quantitative computed tomography (HRpQCT). Cross-sectional and prospective studies, involving a large number of subjects, have both shown that TBS is associated with vertebral, femoral neck, and other types of osteoporotic fractures in postmenopausal women. Data in men, while much less extensive, show similar findings. TBS is also associated with fragility fractures in subjects with secondary causes of osteoporosis, and preliminary data suggest that TBS might improve fracture prediction when incorporated in the fracture risk assessment system known as FRAX. In this article, we review recent advances that have helped to establish this new imaging technology.

TBS (do inglês, “trabecular bone score”) é um novo método que estima a microarquitetura óssea a partir de uma imagem de densitometria óssea (DXA) da coluna lombar. Apesar de o TBS não ser uma medida física direta da microarquitetura trabecular, ele correlaciona-se com o volume ósseo, densidade da conectividade trabecular, número de trabéculas e separação trabecular medidos por microtomografia computadorizada (µCT), e com medidas mecânicas da resistência óssea vertebral em estudos ex vivo. Estudos em humanos confirmaram que o TBS associa-se a microarquitetura trabecular e resistência óssea medidas por tomografia computadorizada quantitativa periférica de alta resolução (HRpQCT). Estudos transversais e prospectivos, envolvendo um grande número de indivíduos, mostraram que o TBS é associado com fratura vertebral, de colo de fêmur e com outros tipos de fraturas osteoporóticas em mulheres na pós-menopausa. Dados em homens, apesar de escassos, mostram resultados semelhantes. Além disso, o TBS foi associado a fraturas por fragilidade em indivíduos com diversas causas secundárias de osteoporose e, dados preliminares, sugerem que o uso do TBS pode melhorar a previsão de fratura quando incorporado ao sistema de avaliação de risco de fratura (FRAX). Este artigo faz uma revisão de avanços recentes que têm ajudado a estabelecer esse novo método de imagem.