Celiac disease and bone

Abstract Celiac disease (CD) is an autoimmune disorder characterized by small intestinal inflammation triggered by gluten ingestion in genetically-predisposed individuals. A frequent extra-intestinal manifestation of CD is metabolic bone disease which contributes to an increased risk of fracture. The mechanisms underlying bone disease in CD remain incompletely understood, but multiple processes have been proposed including (1) malabsorption of calcium and vitamin D leading to secondary hyperparathyroidism and increased skeletal resorption, (2) pro-inflammatory cytokines altering the osteoprotegerin and receptor activator of nuclear kappa-B ligand ratio favoring osteoclastogenesis, (3) hypogonadism, and (4) low weight and malnutrition. Most studies show reduced bone mineral density in patients with CD. Bone microarchitecture is also deteriorated leading to reduced whole bone stiffness. Many, but not all investigations, have shown an increased risk of fracture associated with CD. The main stay of therapy for CD is maintaining a gluten-free diet. Improvement in bone mineral density with adherence to a gluten-free diet has been well-established. Bone mineral density remains lower, however, compared to controls and increased fracture risk can persist. There is no consensus on the timing of dual-energy x-ray absorptiometry for bone mineral density assessment in patients with CD. Routine screening for CD in patients with osteoporosis is not recommended. Little data are available on the use or efficacy of prescription osteoporosis therapeutics in patients with CD. Studies are needed to develop standardized guidelines for screening and treatment of metabolic bone disease in patients with CD to identify those who may need early intervention with prescription osteoporosis therapy. Arch Endocrinol Metab. 2022;66(5):756-64

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.

Observation of the growth and development of subchondral bone in rat condyles exposed to fluoride at the level of bone microarchitecture / 中华地方病学杂志

Objective:To observe the effect of fluoride on growth and development of bone microstructure of rats condyle subchondral bone (RCSB).Methods:Forty two 3-week-old SD rats (half male and half female) were fed adaptively for 1 week, and 3 females and 3 males were sacrificed and recorded as 0 month. The remaining rats were randomly divided into control group ( n = 18) and fluoride exposed group ( n = 18) according to their body weight (55 - 70 g), half male and half female. The fluoride exposed group was fed with 150 mg/L sodium fluoride (NaF) aqueous solution, and the control group was fed with tap water. The two groups of experimental animals were sacrificed at 3, 5 and 7 month, respectively, 6 rats in each group, half male and half female. The right mandibular condyle was separated, and Micro CT scanning was performed to detect the microstructure parameters of RCSB. Results:In fluoride exposed group (3 month), bone surface/tissue volume (BS/TV), bone surface/bone volume (BS/BV), trabecular thickness (Tb.Th), trabecular number (Tb.N), structure model index (SMI), connectivity, connectivity density (Conn.D) and total porosity of female rats were significantly different from those of male rats ( t = - 5.10, - 5.58, 4.52, - 4.32, - 4.03, - 2.81, - 6.71, - 3.32, P < 0.05). There was no significant difference in each index between female and male rats in fluoride exposed group (5, 7 month, P > 0.05). Conclusion:In chronic fluorine exposure bone environment, the RCSB bone microarchitecture of male and female rats is different with time, showing the tendency of fluoride injury that the bone changes of female rats are slowed and the bone changes of male rats are active.

Intrauterine alcohol exposure disturbs trabecular morphology in the Sprague Dawley rat humerus epiphysis up to 3- weeks postnatally / La exposición al alcohol intrauterino altera la morfología trabecular en la epífisis del húmero de la rata Sprague Dawley hasta 3 semanas después del nacimiento

SUMMARY: Gestational alcohol exposure inhibits neurological as well as bone growth and development both in fetal and postnatal life. Stunted stature, osteoporosis and fractures in adult life are some of the adverse effects. While the impact of intrauterine alcohol on the brain has been extensively investigated, studies on the effects on bone are relatively few. Therefore, our study aimed to examine the impact of prenatal alcohol exposure on bone microarchitecture in 3-week-old rats using Micro-focus X-Ray Computed Tomography (Micro CT). Time mated pregnant Sprague Dawley dams (13) were randomly placed into 3 groups: ethanol (n=5), saline control (n=5) and untreated control (n=3). The former 2 groups received treatment with 0.015ml/g of 25.2 % ethanol and 0.9 % saline, respectively, for the first 19 days of gestation. The untreated group received no treatment. The pups remained with their dams until termination at 21 days of age. From each dam, 2 pups were collected resulting in: ethanol (n=10), saline controls (n= 10) and untreated controls (n = 6). The humeri of the pups were dissected and scanned using a 3D-μCT scanner (Nikon XTH 225L) at 15μm resolution. Trabecular and cortical parameters were analysed using Volume Graphics Studio® software following reconstruction. Results showed a decrease in trabecular size, spaces, thickness, and volume. There was a decrease in cortical bone area in the ethanol group compared to the controls. These findings may suggest that osteoporosis and fractures seen as gestational alcohol effects may be due to compromised trabecular structure.

RESUMEN: La exposición al alcohol durante la gestación inhibe el crecimiento y desarrollo neurológico y óseo tanto en la vida fetal como posnatal. Algunos de los efectos adversos incluyen la estatura atrofiada, osteoporosis y fracturas en la vida adulta. Si bien se ha estudiado el impacto del alcohol intrauterino en el cerebro, los estudios sobre los efectos en los huesos son escasos. Por lo tanto, nuestro estudio tuvo como objetivo examinar el impacto de la exposición prenatal al alcohol en la microarquitectura ósea en ratas de 3 semanas de edad utilizando Tomografía Computarizada de Rayos X Micro-focus (Micro CT). Las hembras de Sprague Dawley preñadas con apareamiento temporal (13) se colocaron aleatoriamente en 3 grupos: etanol (n = 5), control de solución salina (n = 5) y control sin tratar (n = 3). Los primeros 2 grupos recibieron tratamiento con 0,015 ml /g de etanol al 25,2 % y solución salina al 0,9 %, respectivamente, durante los primeros 19 días de gestación. El grupo no tratado no recibió tratamiento. Las crías permanecieron con sus madres hasta la terminación a los 21 días de edad. De cada madre, se recolectaron 2 crías que dieron como resultado: etanol (n = 10), controles salinos (n = 10) y controles no tratados (n = 6). Se diseccionaron y escanearon los húmero de las crías usando un escáner 3D-μCT (Nikon XTH 225L) a una resolución de 15 μm. Los parámetros trabeculares y corticales se analizaron utilizando el software Volume Graphics Studio® después de la reconstrucción. Los resultados mostraron una disminución en el tamaño trabecular, los espacios, el grosor y el volumen. Hubo una disminución en el área del hueso cortical en el grupo de etanol en comparación con los controles. Estos hallazgos pueden sugerir que la osteoporosis y las fracturas por causa de los efectos del alcohol gestacional se pueden deber a una estructura trabecular comprometida.

Cortical bone modifications after radiotherapy: cortex porosity and osteonal changes evaluated over time

Abstract Aiming to evaluate cortical bone microarchitecture and osteonal morphology after irradiation, twelve male New Zealand rabbits were used. The animals were divided: control group (no radiation-NIr); and 3 irradiated groups, sacrificed after: 7 (Ir7d); 14 (Ir14d) and 21 (Ir21d) days. A single radiation dose of 30 Gy was used. Computed microtomography analyzed the cortical microarchitecture: cortical thickness (CtTh), bone volume (BV), total porosity (Ct.Po), intracortical porosity (CtPo-cl), channel/pore number (Po.N), fractal dimension (FD) and degree of anisotropy (Ct.DA). After scan, osteonal morphology was histologically assessed by means: area and perimeter of the osteons (O.Ar; O.p) and of the Haversian canals (C.Ar; C.p). Microtomographic analysis were performed by ANOVA, followed by Tukey and Dunnet tests. Osteon morphology analyses were performed by Kruskal-Wallis, and test Dunn's. Cortical thickness was significant difference (p<0.010) between the NIr and irradiated groups, with thicker cortex at Ir7d (1.15±0.09). The intracortical porosity revealed significant difference (p<0.001) between irradiated groups and NIr, with lower value for Ir7d (0.29±0.09). Bone volume was lower in Ir14d compared to control. Area and perimeter of the osteons were statistically different (p<0.0001) between NIr and Ir7d. Haversian canals also revealed lower values (p<0.0001) in Ir7d (80.57±9.3; 31.63±6.5) compared to NIr and irradiated groups. Cortical microarchitecture was affected by radiation, and the effects appear to be time-dependent, mostly regarding the osteons morphology at the initial days. Cortex structure in Ir21d revealed similarities to control suggesting that microarchitecture resembles normal condition after a period.

Resumo Com o objetivo de avaliar a microarquitetura óssea cortical e a morfologia dos osteons após irradiação, foram utilizados doze coelhos machos da Nova Zelândia. Os animais foram divididos: grupo controle (sem radiação-NIr); e 3 grupos irradiados, sacrificados após: 7 (Ir7d); 14 (Ir14d) e 21 (Ir21d) dias. Foi utilizada uma dose única de radiação de 30 Gy. A microtomografia computadorizada analisou a microarquitetura cortical: espessura cortical (CtTh), volume ósseo (BV), porosidade total (Ct.Po), porosidade intracortical (CtPo-cl), número de canal/ poro (Po.N), dimensão fractal (DF) e grau de anisotropia (Ct.DA). Após a varredura, a morfologia dos osteosn foi avaliada histologicamente por meio de: Área e perímetro do osteon (O.Ar; O.p) e dos canais de Havers (C.Ar; C.p). A análise microtomográfica foi realizada por ANOVA, seguida pelos testes de Tukey e Dunnet. As análises morfológicas do osteon foram realizadas por Kruskal-Wallis e testadas por Dunn. A espessura cortical foi diferente (p<0,010) entre os grupos controle e irradiados, com córtex mais espesso no Ir7d (1,15±0,09). A porosidade intracortical revelou diferenças significativas (p<0,001) entre os grupos irradiados e o controle, com menor valor para Ir7d (0,29±0,09). O volume ósseo foi menor no Ir14d em relação ao controle. Área e perímetro do osteon foi diferente (p<0,0001) entre o controle e Ir7d. Os canais haversianos também revelaram valores mais baixos (p<0,0001) em Ir7d (80.57±9.3; 31.63±6.5) em relação ao controle e demais grupos irradiados. A microarquitetura cortical é afetada pela radiação e os efeitos parecem ser dependentes do tempo, principalmente em relação à morfologia dos osteons nos dias iniciais. A estrutura cortical em Ir21d revelou semelhanças com o controle, sugerindo que a microarquitetura se assemelha à condição normal após um período.

Analysis of variation in bone health / 解剖学报

By reviewing the literatures, we retrospectively summarized the human bone mineral variations in ethnicity/race, geography, sex and age and the like, and investigated and summed up the causes of variations in genetics, living styles, bone structure, metabolism etc. It is worth to provide reference for colleagues to study bone health.

Effects of high-fat diet on bone mineral density and microarchitecture in LDLR-/-mice / 中华内分泌代谢杂志

Objective To investigate the effect of high-fat diet on bone calcium content, bone mineral density,and microarchitecture in low density lipoprotein receptor knockout(LDLR-/-) mice. Methods Thirteen LDLR-/- mice aged 11 weeks and 13 sex-age-matched C57BL/6J mice(WT)were divided into WT group with normal diet,WT group with high-fat diet,LDLR-/- group with normal diet,and LDLR-/- group with high-fat diet. All mice were sacrificed at 40 weeks of age and left tibias were harvested to analyze the bone mineral density and bone microarchitecture parameters. The right tibias were sampled for measurement of osteoporogeterin(OPG)and receptor activator of nuclear factor kappa-B ligand(RANKL)mRNA expressions using real-time PCR. Results LDLR-/-and high-fat diet significantly changed bone calcium content, bone microarchitecture parameters, and OPG/RANKL mRNA ratio(P<0.05). Compared with WT mice, LDLR-/-mice with high-fat diet showed a lower bone calcium content,along with correspondingly decreased parameters of bone microarchitecture(P<0.05). Compared with WT mice with normal diet, bone calcium content, tissue bone mineral density, and OPG/RANKL mRNA ratio were decreased in LDLR-/-mice with ordinary diet(P<0.01),while no change of other bone microarchitecture parameters was found. Conclusions High-fat diet results in decreased bone mass and damaged bone microarchitecture in LDLR-/- mice,which may be attributed to the down-regulation of OPG/RANKL mRNA ratio.

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)

An experimental study of effect of curcumin on improvementof bone microarchitecture and bone quality inhigh-fat-diet C57BL/6J mice and its association with cathepsin K / 中国药理学通报

Aim To investigate the effect of curcumin against high-fat-diet induced C57BL/6J mice bone changes and the correlation between the expression of cathepsin K and curcumin.Methods Curcumin treated C57BL/6J mice had been on high fat diet for 12 weeks.The HE, Alizarin red S staining and Safranin O/fast green staining of femur were employed to evaluate bone microstructure, bone metabolism and bone development.The expressions of cathepsin K were assessed by Western blot and immunohistochemical staining.Results Histopathological results showed that curcumin could improve the destruction of trabecular bone structure, cartilage development and bone calcification.Biomechanical results proved that curcumin could improve the bone strength of the type 2 diabetic mice induced by high fat.The results of immunohistochemistry and Western blot assay indicated that curcumin could significantly inhibit the expression of cathepsin K in bone tissues of mice.Conclusion Curcumin can increase bone strength, improve bone microstructure, and enhance the degree of bone calcification, which may be achieved by inhibiting the expression of cathepsin K.

Effect of deer bone polypeptides on bone microarchitecture of dexamethasone-induced osteoporosis rats / 中草药

Objective: To investigate the effect of deer bone polypeptides on bone microarchitecture of dexamethasone-induced osteoporosis (GIOP) rats. Methods: The rats were im given dexamethasone for establishing a rat GIOP model. The rats were ig given deer bone polypeptide with different doses for 75 d. The serum biochemical indexes were classic detection. The three-dimensional analysis of the trabecular structure of proximal tibia was conducted by microCT method; The pathological changes in the morphology of distal femur were observed by hematoxylin. Results: Deer bone polypeptides could increase serum Ca2+ and bone-gla-protein (BGP), decrease serum P3+, alkaline phorphatase (ALP), and parathyroid (PTH) in rats with GIOP. Deer bone polypeptide showed a tendency to reduce the serum CT in rats with GIOP, but the decreasing tendency was not statistically significant compared with the blank control group. The trabecula was thin and ruptured, its free ends increased, its number decreased, its spaces were widened, and the destructed space structures increased in rats with GIOP, while the intervention with deer bone polypeptides could significantly improve the above indexes to evaluate the bone microstructure. Conclusion: Deer bone polypeptides can inhibit the glucocorticoids-induced metabolism imbalance of calcium and phosphorus, reduce the serum ALP, increase the serum BGP, and inhibit the bone resorption and bone formation in rats with GIOP. Moreover, deer bone polypeptides can improve pathological changes in the microstructure and protect osteoporosis rats.

Research on the subchondral bone architecture and bone remodeling related genes change in the initial stage of osteoarthritis in rat / 重庆医学

Objective To investigate the changes of microarchitecture and gene expression of subchondral bone in the initial stage of traumatic arthritis ,to explore the characteristics of subchondral bone remodeling and its role in the articular cartilage de‐generation .Methods The medial meniscal tear (MMT) was performed on the right knees of 13 SD rats to simulate the traumatic osteoarthritis ,while sham operation on the control group .Three weeks later ,all the rats were executed and dissected ,with proximal tibiae being kept and distributed into the two groups ,10 respectively .Micro‐computed tomography (micro‐CT) was adopted to re‐construct and analyze the subchondral bone .After being fixed by 4% paraformaldehyde ,all the samples were decalcified until six weeks passed ,followed by paraffin‐sectioning ,safranin O and fast green staining ,and examining and photographing under an ordina‐ry optical microscope .The RNA of another 3 SD rats′subchondral bone was extracted ,and a real‐time PCR test was carried out to illuminate the expression variation of bone‐formation marker genes (ALP ,RUNX2 ,and OCN) ,and bone‐resorption marker genes (TRAP ,CTSK and MMP9) ,between the two groups .Results Three weeks after MMT surgery ,subchondral bone disorders were observed among the experimental samples through micro‐CT scanning .There was lesser BV/TV ,Conn .D and Tb .Th(P<0 .05) and more Tb .Sp(P<0 .05) in the experimental group compared with the control group .In the pathological section ,arthritic degen‐eration was not spotted in both groups ,but trabeculae of the experimental group were found to be sparse .Compared with control group ,the level of mRNA expression of the bone‐formation marker genes of the experimental group was decreased(P<0 .05) ,while bone‐resorption related genes increased(P<0 .05) .Conclusion The model of initial traumatic osteoarthritis induced by MMT in rats′knees showed an active bone remodeling ,more bone absorbing than bone formation ,lowered bone volume ,and microarchitec‐ture changing of the subchondral bone .

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.

O efeito do ácido zoledrônico na microestrutura óssea analisado pela micro-CT em mandíbulas de ratos wistar / Zoledronic acid effect on the bone microarchitecture of the jaw of rats by Micro-CT

Os bisfosfonatos são medicamentos amplamente e efetivamente utilizados para o tratamento de doenças osteolíticas. Entretanto, na cavidade oral, é de particular relevância, pois possuem como efeito adverso a osteonecrose dos maxilares induzida pelo uso de bisfosfonatos. Sua etiopatogenia ainda não é bem estabelecida, os métodos de detecção são insatisfatórios e as terapias recomendadas são por vezes, medidas paliativas e ineficazes. Pouco ainda é sabido sobre o efeito do Ácido Zoledrônico na microestrutura óssea, portanto, propusemo-nos a realizar um estudo em modelo animal que analisasse o trabeculado ósseo da mandíbula através da Micro-CT. Foram utilizados 24 ratos machos (Rattus novergicus, albinus, Wistar), com 12 semanas de vida, divididos em 2 grupos: grupo controle (cloreto de sódio 0,9%) e grupo ácido zoledrônico (ácido zoledrônico 0,6mg/kg). As substâncias foram administradas via intraperitoneal a cada 28 dias em um total de 5 doses. Após 150 dias do início do experimento, foi realizada a eutanásia dos animais e então as amostras foram preparadas e escaneadas (Skyscan 1174) para análise da microestrutura óssea através da Micro- CT. O teste t-student demonstrou diferença estatisticamente significativa (p<0,05) em todos os fatores: volume ósseo, densidade óssea, fator de padrão trabecular, índice de modelo estrutural, espessura trabecular, separação trabecular, porosidade total exceção de número de trabéculas e volume tecidual, demonstrando que há alterações significativas na estrutura trabecular pelo uso de bisfosfonatos. O grupo medicado com ácido zoledrônico comparado ao grupo controle demonstrou trabéculas mais espessas, menos separadas e com menores ligações...

Bisphosphonates are widely and effectively drugs used for the treatment of osteolytic disorders. However, in the oral cavity, this situation is of particular relevance as it can lead to bisphosphonate related osteonecrosis of the jaws. Its etiopathogenesis is still not established, detection methods are unsatisfactory and recommended therapies are sometimes palliative and often ineffective. Little is known about the effect of zoledronic acid on the quality of trabecular bone, therefore, we proposed to conduct a study in an animal model to examine the trabecular bone of the jaw through the Micro-CT. 24 male rats were used (Rattus norvegicus, Albinus, Wistar), with 12 weeks old, divided into 2 groups: control group (sodium chloride 0.9%) and group with zoledronic acid (zoledronic acid 0.6 mg / kg). The substances were administered intraperitoneally every 28 days for a total of 5 doses. After 150 days from the beginning of the experiment, the animals were sacrificed and then the samples were prepared and scanned (Skyscan 1174) for analysis of the bone microstructure through Micro-CT. The "t-student" test demonstrated statistically significant differences (p<0.05) in all factors: bone volume, osseous density, trabecular pattern, structure model index, trabecular thickness, trabecular separation, total porosity except trabecular number and tissue volume, demonstrating that there are significant changes in the trabecular structure of the bisphosphonates. Zoledronic Acid compared to control group shows thicker, less separate and lower connected trabeculae...

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.

The relationship between microstructure of vertebral cancellous bone and fixation strength of pedicle screws / 医用生物力学

Objective By measuring the microstructure parameters of cancellous bone in vertebral bodies with different bone mineral density (BMD) levels, to study the correlation between such parameters and the corresponding maximum pullout strength (MPS) when fixed by pedicle screws, so as to understand if the microstructure parameters are related with screw stability and further to reveal the cause of screw loosening. Methods Based on the BMD detection results, fresh human cadaver spines were stratified into four levels: normal, osteopenia, osteoporosis and severe osteoporosis, according to diagnosis criteria in clinic. The corresponding vertebral specimens were then instrumented with pedicle screws, and screw pullout tests were conducted to measure the MPS of such screws. All the vertebral specimens were collected subsequently, and the cancellous bone cylinders were drilled from the center of each vertebra for micro CT scanning. Microstructure parameters of the vertebral trabecular bone at different BMD levels were obtained to investigate the interrelationships in between, and the relationships between the microstruture parameters and corresponding MPS of pedicle screws with osteoporosis severity were then compared. Results With the decline of BMD from normal to severe osteoporosis level, the corresponding MPS of pedicle screws was significantly declined. With the severity of osteoporosis increasing, the progressive bone volume loss, mechanical incompetence and microstructure deterioration also appeared evidently. Significant differences were found in microstructure parameters at different BMD levels. Strong correlations were extensively observed among BMD, microstructure parameters and MPS of screws. The MPS of pedicle screws was highly correlated with bone volume over total volume (BV/TV), trabecular thickness (Tb.Th) and trabecular separation (Tb.Sp) from micro-CT scanning. Conclusions Significant deterioration would occur in bone tissues with the decline of BMD level, and the MPS of pedicle screws was highly correlated with some microstructure parameters.

Efectos "in vivo" de Metformina sobre las alteraciones de la microarquitectura sea asociadas al Sndrome Metablico inducido por fructosa en ratas / In vivo effects of Metformin on the alterations of bone micro-architecture associated with fructose-induced Metabolic Syndrome in rats

El Sndrome Metablico (SM) se ha asociado recientemente con una disminucin en la densidad mineral sea, y con un aumento en la incidencia de fracturas osteoporticas. Recientemente encontramos que la Metformina por va oral en ratas, promueve la diferenciacin osteognica de clulas progenitoras de mdula sea e incrementa la reparacin de lesiones seas. En este trabajo evaluamos los efectos del SM inducido por Fructosa sobre la microarquitectura sea en ratas, y la modulacin de estos efectos por Metformina administrada en forma oral. Utilizamos ratas Sprague Dawley macho jvenes: C (control sin tratamiento), C+M (100mg/kg/da Metformina en el agua de bebida), F (10 % Fructosa en el agua de bebida) y F+M (Fructosa+Metformina en el agua de bebida). Los tratamientos se continuaron por 3 semanas luego de lo cual se tomaron muestras de sangre, previas al sacrificio de los animales. Se disecaron los fmures para evaluacin histomorfomtrica de la microarquitectura metafisaria por tincin con Hematoxilina-Eosina (H-E). Se observ un incremento en la glucemia y trigliceridemia en el grupo F versus el C, compatible con el desarrollo de SM. El anlisis de las metfisis femorales mostr un aumento en la densidad osteoctica trabecular para el grupo C+M (118 % del control, p<0,05). El tratamiento con Fructosa sola disminuy la densidad osteoctica (79 % del control, p<0,05), mientras que el co-tratamiento Fructosa+Metformina (grupo F+M) revirti parcialmente este descenso (88 % del control). Similarmente, el porcentaje de hueso trabecular en la metfisis femoral aument luego del tratamiento slo con Metformina (129 % respecto del control), se redujo en las ratas tratadas con Fructosa (89 % respecto del control), y fue intermedia en el grupo F+M (94 % respecto del control). Estos resultados muestran que el SM inducido por Fructosa en ratas altera la microarquitectura metafisaria femoral; y que estos efectos deletreos pueden ser parcialmente prevenidos por un tratamiento oral con Metformina.

Several clinical studies have demonstrated that the Metabolic Syndrome (MS) is associated with a decrease in bone mineral density, and with an increased risk for non-vertebral osteoporotic fractures. We have recently found that orally administered Metformin induces osteogenic effects in rats, promoting osteoblastic differentiation of bone marrow progenitor cells and increasing the repair of bone lesions. In the present work we have evaluated the effects of Fructose-induced MS on bone micro-architecture in rats, and the possible modulation of these effects by orally administered Metformin. We utilized young male Sprague-Dawley rats, divided into four groups: C (non-treated controls); C+M (100 mg/kg/day of Metformin in drinking water); F (10 % of Fructose in drinking water); and F+M (Fructose+Metformin in drinking water). After three weeks of all treatments blood samples were taken, after which animals were sacrificed by cervical dislocation under anaesthesia. Femurs were then dissected for evaluation of metaphyseal micro-architecture after Haematoxilin-Eosin staining of 5 μm histological slices of decalcified bone. In particular, osteocytic density and relative trabecular volume were determined. An increase in serum glucose and triglycerides was observed in Fructose-treated rats, in accordance with the development of MS. In rats treated with Metformin alone (group C+M), the analysis of femoral metaphyses showed an increase in trabecular osteocytic density (118 % of control [group C], p<0.05). Treatment with Fructose alone (group F) significantly decreased ostecytic density (79 % of control, p<0.05), while co-treatment with Fructose and Metformin partially reverted this decrease (group F+M, 88 % of control). Similarly, the relative trabecular volume of femoral metaphysic was increased by treatment with Metformin alone (129% of control), was reduced in Fructose-treated rats (89 % of control), and tended to revert back to control values after Fructose-Metformin co-treatment (94 % of control). These results show for the first time that (a) Fructose-induced MS in rats alters their femoral metaphysis micro-architecture; and that (b) these deleterious effects can be partially prevented by orally administered Metformin.

Effect of a Long-term, Oral Fixed Dose with a Combination of Aledronate and Cacitriol on the Cancellous Bone Microarchitecture in Ovariectomized Rats / 대한정형외과연구학회지

PURPOSE: To study the effect of a long-term, oral, fixed dose with a combination of alendronate and calcitriol on the cancellous bone microarchitecture in an ovariectomized rat model. MATERIALS AND METHODS: Twenty eight female Sprague-Dawley rats were divided into 2 equal groups: a non-medication group (OVX), and a medication group (ALD). The ALD group was treated with an oral daily fixed dose with a combination of alendronate and calcitriol for six months, starting from 4 weeks after ovariectomy, while the OVX group was given only a placebo. After six months, all animals were sacrificed, and an in vitro micro-CT analysis of the the distal femur was performed. The bone volume fraction (BV/TV), trabecular thickness (Tb.Th), trabecular separation (Tb.Sp), trabecular number (Tb.N), structure model index (SMI), connectivity density (Conn.D), and bone mineral density (BMD) were assessed. RESULTS: The ALD group had significantly higher BV/TV, Tb N, BMD and Conn.D and it also had significantly lower Tb Sp and SMI than the OVX group. CONCLUSION: A long term, daily, oral fixed dose with a combination of alendronate and calcitriol could significantly reduce the osteoporotic changes in this ovariectomized rat model.

Morphometric Analysis of Tibial Bone in Three Strains of Mice Using Micro-computed Tomography / 한국실험동물학회지

This study investigated the trabecular and cortical bone microarchitecture of tibia in 14-week-old C3H/HeN, C57BL/6J and ICR mice using micro-computed tomography (micro-CT). Defined volumes of interest were scanned at a resolution of 17 micrometer (isotropic). The X-ray tube was set at photon energy of 50 kV, current of 200 microA, exposure time 1.2 sec, and a 0.5 mm-thick aluminium filter. For quantification of bone mineral density (BMD), the bone samples were scanned by micro-CT together with 2 calibration phantoms. The image slices were reconstructed using 3-dimensional CT analyzer software. C3H/HeN mice showed significantly higher levels of bone volume fraction, trabecular number and BMD, and lower levels of trabecular separation, structure model index and degree of anisotropy compared to C57BL/6J or ICR mice in trabecular bone area. So the C3H/HeN mouse appeared to be a good model animal for the study on the changes of trabecular bone with high trabecular bone mass.

Morphometric Analysis of Tibial Bone in Three Strains of Mice Using Micro-computed Tomography / 한국실험동물학회지

This study investigated the trabecular and cortical bone microarchitecture of tibia in 14-week-old C3H/HeN, C57BL/6J and ICR mice using micro-computed tomography (micro-CT). Defined volumes of interest were scanned at a resolution of 17 micrometer (isotropic). The X-ray tube was set at photon energy of 50 kV, current of 200 microA, exposure time 1.2 sec, and a 0.5 mm-thick aluminium filter. For quantification of bone mineral density (BMD), the bone samples were scanned by micro-CT together with 2 calibration phantoms. The image slices were reconstructed using 3-dimensional CT analyzer software. C3H/HeN mice showed significantly higher levels of bone volume fraction, trabecular number and BMD, and lower levels of trabecular separation, structure model index and degree of anisotropy compared to C57BL/6J or ICR mice in trabecular bone area. So the C3H/HeN mouse appeared to be a good model animal for the study on the changes of trabecular bone with high trabecular bone mass.

Roles of Orphan Nuclear Receptor Small Heterodimer Partner in Bone Development: Microcomputed Tomographic Analysis of Bone Microarchitecture in SHP Knockout Mice / 대한골다공증학회지

OBJECTIVES: Orphan nuclear receptor small heterodimer partner (SHP) is involved in osteoblastic differentiation. This study was undertaken to demonstrate a role of SHP in in vivo bone development using microcomputed tomographic (microCT) analysis of SHP knockout (KO) mice. MATERIAL & METHODS: Tibia bones were harvested from 1-, 4-, 8- and 20-week-old wild type (WT) and SHP KO mice. The microarchitecture of tibial bone was analyzed using a microCT (Skyscan 1172; Skyscan, Kontich, Belgium). Samples were scanned at a resolution of 17 microm (isotropic). The X-ray was operated with 50 kV, 200 microA of energy, 1.2 sec of exposure time, and a 0.5 mm thick aluminum filter. Projections were acquired over an angular range of 180degrees. For quantification of the bone mineral density (BMD), the microCT was calibrated using 2 standard phantoms with densities of 0.25 and 0.75 g/cm3. The image slices were reconstructed and analyzed using CT analyzer software (CTan, Skyscan). RESULTS: The CT values of tibial trabecular bone were significantly decreased in SHP KO compared to WT at 20-week-old mice determined by microCT; (bone volume / tissue volume [BV/TV, 40%], BMD [80%], and trabecular number [Tb.N, 50%]). However, the CT values were not significantly different between WT and SHP KO in cortical bone. Furthermore, the qualitative indices of trabecular bone such as the structure model index (SMI) and the polar moment inertia (PMI) did not differ between WT and SHP KO mice. CONCLUSION: These microCT results supports that SHP may act as a positive regulator of trabecular bone formation.