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.

Circulating sclerostin and estradiol levels are associated with inadequate response to bisphosphonates in postmenopausal women with osteoporosis.

INTRODUCTION: The biological mechanisms associated with an inadequate response to treatment with bisphosphonates are not well known. This study investigates the association between circulating levels of sclerostin and estradiol with an inadequate clinical outcome to bisphosphonate therapy in women with postmenopausal osteoporosis. METHODS: This case-control study is based on 120 Spanish women with postmenopausal osteoporosis being treated with oral bisphosphonates. Patients were classified as adequate responders (ARs, n=66, mean age 68.2±8 years) without incident fractures during 5 years of treatment, or inadequate responders (IRs, n=54, mean age 67±9 years), with incident fractures between 1 and 5 years of treatment. Bone mineral density (DXA), structural analysis of the proximal femur and structural/fractal analysis of the distal radius were assessed. Sclerostin concentrations were measured by ELISA and 17ß-estradiol levels by radioimmunoassay based on ultrasensitive methods. RESULTS: In the ARs group, sclerostin serum levels were significantly lower (p=0.02) and estradiol concentrations significantly higher (p=0.023) than in the IRs group. A logistic regression analysis was performed, including as independent variables in the original model femoral fracture load, 25 hydroxyvitamin D, previus history of fragility fracture, sclerostin and estradiol. Only previous history of fragility fracture (OR 14.04, 95% CI 2.38-82.79, p=0.004) and sclerostin levels (OR 1.11, 95% CI 1.02-1.20, p=0.011), both adjusted by estradiol levels remained associated with IRs. Also, sclerostin concentrations were associated with the index of resistance to compression (IRC) in the fractal analysis of the distal radius, a parameter on bone microstructure. CONCLUSIONS: Sclerostin and estradiol levels are associated with the response to bisphosphonate therapy in women with postmenopausal osteoporosis.

3D segmentation of annulus fibrosus and nucleus pulposus from T2-weighted magnetic resonance images.

Computational medicine aims at employing personalised computational models in diagnosis and treatment planning. The use of such models to help physicians in finding the best treatment for low back pain (LBP) is becoming popular. One of the challenges of creating such models is to derive patient-specific anatomical and tissue models of the lumbar intervertebral discs (IVDs), as a prior step. This article presents a segmentation scheme that obtains accurate results irrespective of the degree of IVD degeneration, including pathological discs with protrusion or herniation. The segmentation algorithm, employing a novel feature selector, iteratively deforms an initial shape, which is projected into a statistical shape model space at first and then, into a B-Spline space to improve accuracy.The method was tested on a MR dataset of 59 patients suffering from LBP. The images follow a standard T2-weighted protocol in coronal and sagittal acquisitions. These two image volumes were fused in order to overcome large inter-slice spacing. The agreement between expert-delineated structures, used here as gold-standard, and our automatic segmentation was evaluated using Dice Similarity Index and surface-to-surface distances, obtaining a mean error of 0.68 mm in the annulus segmentation and 1.88 mm in the nucleus, which are the best results with respect to the image resolution in the current literature.

Genetic analysis of high bone mass cases from the BARCOS cohort of Spanish postmenopausal women.

The aims of the study were to establish the prevalence of high bone mass (HBM) in a cohort of Spanish postmenopausal women (BARCOS) and to assess the contribution of LRP5 and DKK1 mutations and of common bone mineral density (BMD) variants to a HBM phenotype. Furthermore, we describe the expression of several osteoblast-specific and Wnt-pathway genes in primary osteoblasts from two HBM cases. A 0.6% of individuals (10/1600) displayed Z-scores in the HBM range (sum Z-score >4). While no mutation in the relevant exons of LRP5 was detected, a rare missense change in DKK1 was found (p.Y74F), which cosegregated with the phenotype in a small pedigree. Fifty-five BMD SNPs from Estrada et al. [NatGenet 44:491-501,2012] were genotyped in the HBM cases to obtain risk scores for each individual. In this small group of samples, Z-scores were found inversely related to risk scores, suggestive of a polygenic etiology. There was a single exception, which may be explained by a rare penetrant genetic variant, counterbalancing the additive effect of the risk alleles. The expression analysis in primary osteoblasts from two HBM cases and five controls suggested that IL6R, DLX3, TWIST1 and PPARG are negatively related to Z-score. One HBM case presented with high levels of RUNX2, while the other displayed very low SOX6. In conclusion, we provide evidence of lack of LRP5 mutations and of a putative HBM-causing mutation in DKK1. Additionally, we present SNP genotyping and expression results that suggest additive effects of several genes for HBM.

Densitometría ósea y medicina nuclear / Bone densitometry and Nuclear Medicine

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