Do the negative symptoms of schizophrenia reflect reduced responsiveness to reward? Examination using a reward prediction error (RPE) task.

BACKGROUND: A leading theory of the negative symptoms of schizophrenia is that they reflect reduced responsiveness to rewarding stimuli. This proposal has been linked to abnormal (reduced) dopamine function in the disorder, because phasic release of dopamine is known to code for reward prediction error (RPE). Nevertheless, few functional imaging studies have examined if patients with negative symptoms show reduced RPE-associated activations. METHODS: Matched groups of DSM-5 schizophrenia patients with high negative symptom scores (HNS, N = 27) or absent negative symptoms (ANS, N = 27) and healthy controls (HC, N = 30) underwent fMRI scanning while they performed a probabilistic monetary reward task designed to generate a measure of RPE. RESULTS: In the HC, whole-brain analysis revealed that RPE was positively associated with activation in the ventral striatum, the putamen, and areas of the lateral prefrontal cortex and orbitofrontal cortex, among other regions. Group comparison revealed no activation differences between the healthy controls and the ANS patients. However, compared to the ANS patients, the HNS patients showed regions of significantly reduced activation in the left ventrolateral and dorsolateral prefrontal cortex, and in the right lingual and fusiform gyrus. HNS and ANS patients showed no activation differences in ventral striatal or midbrain regions-of-interest (ROIs), but the HNS patients showed reduced activation in a left orbitofrontal cortex ROI. CONCLUSIONS: The findings do not suggest that a generalized reduction of RPE signalling underlies negative symptoms. Instead, they point to a more circumscribed dysfunction in the lateral frontal and possibly the orbitofrontal cortex.

Processing of linguistic deixis in people with schizophrenia, with and without auditory verbal hallucinations.

Auditory verbal hallucinations (AVH) are a key symptom of schizophrenia (SZ) defined by anomalous perception of speech. Anomalies of processing external speech stimuli have also been reported in people with AVH, but it is unexplored which specific dimensions of language are processed differently. Using a speech perception task (passive listening), we here targeted the processing of deixis, a key dimension of language governing the contextual anchoring of speech in interpersonal context. We designed naturalistic speech stimuli that were either non-personal and fact-reporting ('low-deixis' condition), or else involved rich deictic devices such as the grammatical first and second persons, direct questions, and vocatives ('high-deixis'). We asked whether neural correlates of deixis obtained with fMRI would distinguish patients with and without frequent hallucinations (AVH + vs AVH-) from controls and each other. Results showed that high-deixis relative to low-deixis was associated with clusters of increased activation in the bilateral middle temporal gyri extending into the temporal poles and the inferior parietal cortex, in all groups. The AVH + and AVH- groups did not differ. When unifying them, the SZ group as a whole showed altered activity in the precuneus, midline regions and inferior parietal cortex. These results fail to confirm deictic processing anomalies specific to patients with AVH, but reveal such anomalies across SZ. Hypoactivation of this network may relate to a cognitive mechanism for attributing and anchoring thought and referential speech content in context.

Microstructural and Strength Changes in Trabecular Bone in Elderly Patients with Type 2 Diabetes Mellitus.

Type 2 diabetes mellitus (T2DM) is one of the most common chronic diseases worldwide and it is associated with an increased risk of osteoporosis and fragility fractures. Our aim is to analyze the effect of T2DM on bone quality. This is a case-control study. The studied population consisted of 140 patients: 54 subjects with hip fracture (OP) without T2DM, 36 patients with hip fracture and T2DM (OP-T2DM), 28 patients with osteoarthritis (OA) without T2DM, and 22 patients with OA and T2DM (OA-T2DM). Bone markers, bone mineral density, FRAX score, microstructural, and bone material strength from femoral heads were assessed. The group with hip fracture presented lower BMD values than OA (p < 0.05). The OP, OP-T2DM, and OA-T2DM groups showed a decrease in bone volume fraction (BV/TV), in trabecular number (Tb.N), and in trabecular thickness (Tb.Th), while an increase was presented in the structural model index (SMI) and trabecular bone pattern factor (Tb.Pf), The groups OP, OP-T2DM, and OA-T2DM also presented lower values than those in group OA regarding the biomechanical parameters in the form of Young's modulus or elastic modulus, toughness, ultimate stress, ultimate load, extrinsic stiffness, and work to failure (p < 0.05). Our results show the negative effect of type 2 diabetes mellitus on trabecular bone structure and mechanical properties.

The BAT: A videotaped battery to assess theory of mind in schizophrenia.

The ability of attributing mental states to oneself and to the others (theory of mind, ToM) is impaired in schizophrenia. ToM is not a monolithic function, it includes different capacities: some implies the decoding of affective states, others the reasoning about mental states. We have developed the BAT, a Battery to Assess Theory of mind abilities in adult psychotic subjects in an ecological audiovisual format. The performance on the BAT and three other test of social cognition was compared in a sample of schizophrenic patients with a control group. The samples were matched in terms of age and premorbid IQ. The BAT was sensitive to detect the ToM impairments in schizophrenia, showed good internal consistency and concurrent validity. The area under the ROC curves established a cutoff point that would correctly classify controls and patients in a 96.6% of cases. The factorial analysis isolated two factors: empathy and reasoning, with a good adjustment. Our results showed that the BAT could be a valid, ecological and usable tool to assess ToM in psychotic patients, with good psychometric properties, that would allow obtaining a more complete profile of their impairment.

Efecto del tratamiento con calcifediol, sobre los episodios cardiovasculares en pacientes revascularizados tras síndrome coronario agudo / Effect of calcifediol treatment on cardiovascular outcomes in patients with acute coronary syndrome and percutaneous revascularization

Antecedentes y objetivos: El déficit de 25(OH)D se ha relacionado con un riesgo cardiovascular aumentado, aunque los estudios de intervención son contradictorios. El objetivo principal fue evaluar el efecto del tratamiento con calcifediol (25(OH)D3) sobre el sistema cardiovascular en pacientes con síndrome coronario agudo sin elevación de segmento ST. Pacientes y método: Estudio prospectivo que incluyó a 41 pacientes (70,6±6,3 años) ≥60 años con síndrome coronario agudo sin elevación de segmento ST y enfermedad coronaria revascularizada percutáneamente. Se aleatorizaron a recibir calcifediol+tratamiento habitual o tratamiento habitual exclusivo, con evaluación de major adverse cardiovascular events (MACE, «episodios cardiovasculares mayores adversos») a los 3 meses. Se estudió la 25(OH)D en relación con otras variables analíticas y con la extensión de la enfermedad coronaria. Resultados: Niveles basales de 25(OH)D≤50nmol/l se asociaron a enfermedad coronaria multivaso (RR: 2,6 [IC 95%: 1,1-7,1], p=0,027) y 25(OH)D≤50nmol/l+paratohormona≥65pg/ml identificaron a pacientes con mayor riesgo de MACE (RR: 4 [IC 95%: 1,1-21,8], p=0,04). Se registró un MACE en el grupo de pacientes suplementados y 5 en el de tratamiento convencional (p=0,66). Entre los pacientes con niveles séricos de 25(OH)D≤50nmol/l al final del estudio el 28,6% presentaron MACE frente al 0% si los niveles eran>50nmol/l (RR: 1,4; p=0,037). Conclusiones: El déficit de vitamina D que implica un hiperparatiroidismo secundario puede ser un buen predictor de MACE. En pacientes suplementados con calcifediol se observó una tendencia a la disminución de MACE en el seguimiento. Niveles finales de 25(OH)D≤50nmol/l se asociaron significativamente a un mayor número de MACE, por lo que la normalización de 25(OH)D, además de mejorar la salud ósea, puede mejorar la salud cardiovascular

Background and objectives: Vitamin D deficiency has been consistently linked with cardiovascular diseases. However, results of intervention studies are contradictory. The aim of this study was to evaluate the effect of treatment with calcifediol (25(OH)D3) on the cardiovascular system of patients with non-ST-elevation acute coronary syndrome after percutaneous coronary intervention. Patients and methods: A prospective study assessing≥60-year-old patients with non-ST-elevation acute coronary syndrome, coronary artery disease and percutaneous revascularisation. We randomly assigned 41 patients (70.6±6.3 years) into 2 groups: Standard treatment+25(OH)D3 supplementation or standard treatment alone. Major adverse cardiovascular events (MACE) were evaluated at the conclusion of the 3-month follow-up period. 25(OH)D levels were analysed with regard to other relevant analytical variables and coronary disease extent. Results: Basal levels of 25(OH)D≤50nmol/L were associated with multivessel coronary artery disease (RR: 2.6 [CI 95%:1.1-7.1], P=.027) and 25(OH)D≤50nmol/L+parathormone ≥65pg/mL levels correlated with increased risk for MACE (RR: 4 [CI 95%: 1.1-21.8], P=.04]. One MACE was detected in the supplemented group versus five in the control group (P=.66). Among patients with 25(OH)D levels≤50nmol/L at the end of the study, 28.6% had MACE versus 0% among patients with 25(OH)D>50nmol/L (RR: 1,4; P=.037). Conclusions: Vitamin D deficiency plus secondary hyperparathyroidism may be an effective predictor of MACE. A trend throughout the follow up period towards a reduction in MACE among patients supplemented with 25(OH)D3 was detected. 25(OH)D levels≤50nmol/L at the end of the intervention period were significantly associated with an increased number of MACE, hence, 25(OH)D level normalisation could improve cardiovascular health in addition to bone health

Effect of calcifediol treatment on cardiovascular outcomes in patients with acute coronary syndrome and percutaneous revascularization. / Efecto del tratamiento con calcifediol, sobre los episodios cardiovasculares en pacientes revascularizados tras síndrome coronario agudo.

BACKGROUND AND OBJECTIVES: Vitamin D deficiency has been consistently linked with cardiovascular diseases. However, results of intervention studies are contradictory. The aim of this study was to evaluate the effect of treatment with calcifediol (25(OH)D3) on the cardiovascular system of patients with non-ST-elevation acute coronary syndrome after percutaneous coronary intervention. PATIENTS AND METHODS: A prospective study assessing≥60-year-old patients with non-ST-elevation acute coronary syndrome, coronary artery disease and percutaneous revascularisation. We randomly assigned 41 patients (70.6±6.3 years) into 2 groups: Standard treatment+25(OH)D3 supplementation or standard treatment alone. Major adverse cardiovascular events (MACE) were evaluated at the conclusion of the 3-month follow-up period. 25(OH)D levels were analysed with regard to other relevant analytical variables and coronary disease extent. RESULTS: Basal levels of 25(OH)D≤50nmol/L were associated with multivessel coronary artery disease (RR: 2.6 [CI 95%:1.1-7.1], P=.027) and 25(OH)D≤50nmol/L+parathormone ≥65pg/mL levels correlated with increased risk for MACE (RR: 4 [CI 95%: 1.1-21.8], P=.04]. One MACE was detected in the supplemented group versus five in the control group (P=.66). Among patients with 25(OH)D levels≤50nmol/L at the end of the study, 28.6% had MACE versus 0% among patients with 25(OH)D>50nmol/L (RR: 1,4; P=.037). CONCLUSIONS: Vitamin D deficiency plus secondary hyperparathyroidism may be an effective predictor of MACE. A trend throughout the follow up period towards a reduction in MACE among patients supplemented with 25(OH)D3 was detected. 25(OH)D levels≤50nmol/L at the end of the intervention period were significantly associated with an increased number of MACE, hence, 25(OH)D level normalisation could improve cardiovascular health in addition to bone health.

SNPs in bone-related miRNAs are associated with the osteoporotic phenotype.

Biogenesis and function of microRNAs can be influenced by genetic variants in the pri-miRNA sequences leading to phenotypic variability. This study aims to identify single nucleotide polymorphisms (SNPs) affecting the expression levels of bone-related mature microRNAs and thus, triggering an osteoporotic phenotype. An association analysis of SNPs located in pri-miRNA sequences with bone mineral density (BMD) was performed in the OSTEOMED2 cohort (n = 2183). Functional studies were performed for assessing the role of BMD-associated miRNAs in bone cells. Two SNPs, rs6430498 in the miR-3679 and rs12512664 in the miR-4274, were significantly associated with femoral neck BMD. Further, we measured these BMD-associated microRNAs in trabecular bone from osteoporotic hip fractures comparing to non-osteoporotic bone by qPCR. Both microRNAs were found overexpressed in fractured bone. Increased matrix mineralization was observed after miR-3679-3p inhibition in human osteoblastic cells. Finally, genotypes of rs6430498 and rs12512664 were correlated with expression levels of miR-3679 and miR-4274, respectively, in osteoblasts. In both cases, the allele that generated higher microRNA expression levels was associated with lower BMD values. In conclusion, two osteoblast-expressed microRNAs, miR-3679 and miR-4274, were associated with BMD; their overexpression could contribute to the osteoporotic phenotype. These findings open new areas for the study of bone disorders.

Influence of high glucose and advanced glycation end-products (ages) levels in human osteoblast-like cells gene expression.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is associated with an increased risk of osteoporotic fracture. Several factors have been identified as being potentially responsible for this risk, such as alterations in bone remodelling that may have been induced by changes in circulating glucose or/and by the presence of non-oxidative end products of glycosylation (AGEs). The aim of this study is to assess whether such variations generate a change in the gene expression related to the differentiation and osteoblast activity (OPG, RANKL, RUNX2, OSTERIX, and AGE receptor) in primary cultures of human osteoblast-like cells (hOB). METHODS: We recruited 32 patients; 10 patients had osteoporotic hip fractures (OP group), 12 patients had osteoporotic hip fractures with T2DM (T2DM group), and 10 patients had hip osteoarthritis (OA group) with no osteoporotic fractures and no T2DM. The gene expression was analyzed in hOB cultures treated with physiological glucose concentration (4.5 mM) as control, high glucose (25 mM), and high glucose plus AGEs (2 µg/ml) for 24 h. RESULTS: The hOB cultures from patients with hip fractures presented slower proliferation. Additionally, the hOB cultures from the T2DM group were the most negatively affected with respect to RUNX2 and OSX gene expression when treated solely with high glucose or with high glucose plus AGEs. Moreover, high levels of glucose induced a major decrease in the RANKL/OPG ratio when comparing the OP and the T2DM groups to the OA group. CONCLUSIONS: Our data indicates an altered bone remodelling rate in the T2DM group, which may, at least partially, explain the reduced bone strength and increased incidence of non-traumatic fractures in diabetic patients.

Conocimientos y aptitudes del personal sanitario frente a sospecha de caso de enfermedad por el virus del Ébola / Knowledge and attitudes of healthcare workers towards a suspect case of Ebola virus disease

Introducción. El último brote de la enfermedad por el virus del Ébola, constituyó un precedente a la hora de evidenciar la necesaria formación del personal sanitario para posibles eventualidades de casos sospechosos de enfermedades contagiosas. Se precisa estudiar el nivel de cualificación del personal sanitario ante dichas situaciones. Material y métodos. Estudio descriptivo mediante encuesta post-taller al personal sanitario de un departamento de salud de la Comunidad Valenciana sobre los conocimientos y aptitudes adquiridos tras la formación. Resultados y conclusiones. El personal sanitario obtuvo una calificación global de aprobado en la encuesta post-taller, pero con diferencias en cuanto a categorías profesionales y distintos bloques de la formación, cuyas calificaciones podrían ser consideradas como deficientes en algunos casos. Se debería revisar la formación del personal sanitario periódicamente y calibrar dicha formación a los recursos de los que se dispone para una correcta actuación (AU)

Introduction. The last outbreak of the Ebola virus disease, was a precedent to demonstrate the necessary training of healthcare personnel for possible eventualities of suspected cases of infectious diseases. It is required to study the level of qualification of healthcare workers in such situations. Methods. Descriptive study using post-workshop survey of healthcare workers in a Valencian Community health department on acquired knowledge and skills after training. Results and conclusions. Healthcare personnel received an overall passing score on the post-workshop survey, but with differences in occupational categories and different blocks of training. The ratings could be considered deficient in some cases. It should be reviewed periodically training health personnel and calibrate such training to the resources available for proper operation (AU)

Reflexionando con Benito Menni en el siglo XXI / No disponible

En la situación actual de crisis económica es fácil que a nivel asistencial se presenten conflictos entre distintos valores hospitalarios, debiendo priorizar unos por encima de otros. Ante esa situación se decide estudiar e investigar los valores a los que San Benito Menni daba mayor prioridad, es decir su jerarquía de valores. Para ello, se constituyó un grupo de reflexión que, a través del estudio de la abundante documentación epistolar referida al padre Menni y su enmarque en las diferencias entre el escenario socioeconómico-cultural de finales del siglo XIX y el actual, propone una metodología de consenso deductiva-inductiva cuya síntesis es una carta consejo del padre Menni dirigida a los problemas y conflictos actuales (AU)

In the current economic crisis, conflicts between different hospital values are presented. Given this situation it was decided to study and investigate the hierarchy of values of San Benito Menni. A think tank that studied the abundant epistolary documentation referred to Father Menni and its historical context and cultural socio-economic scenario (late nineteenth century and early twentyfirst century) was formed. This group uses a methodology of deductive-inductive consensus whose synthesis is a Father Menni letter addressed to current conflicts (AU)

[Knowledge and attitudes of healthcare workers towards a suspect case of Ebola virus disease]. / Conocimientos y aptitudes del personal sanitario frente a sospecha de caso de enfermedad por el virus del Ébola.

OBJECTIVE: The last outbreak of the Ebola virus disease, was a precedent to demonstrate the necessary training of healthcare personnel for possible eventualities of suspected cases of infectious diseases. It is required to study the level of qualification of healthcare workers in such situations. METHODS: Descriptive study using post-workshop survey of healthcare workers in a Valencian Community health department on acquired knowledge and skills after training. CONCLUSIONS: Healthcare personnel received an overall passing score on the post-workshop survey, but with differences in occupational categories and different blocks of training. The ratings could be considered deficient in some cases. It should be reviewed periodically training health personnel and calibrate such training to the resources available for proper operation.

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.

Response to Denosumab Treatment for 2 Years in an Adolescent With Osteoradionecrosis.

Radiotherapy, an essential component of cancer treatment, is not without risk to bone, particularly to the immature or growing skeleton. Known side effects range from post-radiation osteitis to osteoradionecrosis. We report the case of a 14-year-old male patient undergoing denosumab treatment, a new antiresorptive agent, for osteoradionecrosis. The patient exhibited fractures and associated pain and functional limitations secondary to radiation for the treatment of an embryonal rhabdomyosarcoma of prostate grade III administered at age 5 years. After treatment with denosumab, the pain disappeared, bone remodeling markers dramatically declined, bone mass increased, and pathological bone scan findings resolved without adverse effects or new fractures.

POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy and skin changes) treated with autologous hematopoietic stem cell transplantation: a case report and literature review.

BACKGROUND: POEMS syndrome is a rare systemic pathology of paraneoplastic origin that is associated with plasma cell dyscrasia. It is characterized by the presence of sensorimotor polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, skin changes, and other systemic manifestations. The pathogenesis of the syndrome is unknown but over-production of vascular endothelial growth factor is probably responsible for most of the more characteristic symptoms. There is no standard treatment for POEMS syndrome and no randomized controlled clinical trials of treatment exist in the available literature. High-dose melphalan with autologous hematopoietic stem cell transplantation should be considered for younger patients with widespread osteosclerotic lesions, and for patients with rapidly progressive neuropathy. CASE REPORT: This is the case of a 62-year-old Caucasian man who was admitted to our center presenting pretibial edema accompanied by significant weight loss and difficulty walking. POEMS criteria were present and an immunofixation test confirmed the presence of a monoclonal plasmaproliferative disorder. After autologous hematopoietic stem cell transplantation, the monoclonal component disappeared and the patient's clinical status improved markedly. CONCLUSIONS: Autologous hematopoietic stem cell transplantation following high-dose melphalan is an effective therapy for younger patients with widespread osteosclerotic lesions in POEMS syndrome.

Microstructural trabecular bone from patients with osteoporotic hip fracture or osteoarthritis: its relationship with bone mineral density and bone remodelling markers.

Osteoporosis (OP) and osteoarthritis (OA) are the most prevalent musculoskeletal disorders in the elderly but the relationship between them is unclear. The purposes of this study are to analyze the bone turnover markers (BTM), bone mineral density (BMD) and the structural and mechanical properties of trabecular bone in patients with OP and OA, and to explore the relationship between these two diseases. We studied 12 OP patients and 13 OA patients. We analyzed BTM (ß-CrossLaps and PINP), BMD and microstructural and biomechanical parameters (micro-CT). Our results were: OP group has higher levels of ß-CrossLaps and lower BMD at the femoral neck. Also, OP patients have a decreased volume of trabecular bone and less trabecular number, with architecture showing prevalence of rod-like trabeculae and worse connectivity than OA patients. The biomechanical parameters were worse in OP patients. BMD was correlated with almost all the structural and biomechanical parameters. Moreover, ß-CrossLaps was negatively correlated with hip BMD and with bone surface density and positively with trabecular separation. BTM, BMD and bone microstructural changes in osteoporosis are opposite to those of OA. These findings justify a less resistant bone with higher risk of fragility fractures in OP patients. These histomorphometric and biomechanical changes may be suspected by measuring of BMD and ß-CrossLaps levels.

Immunotherapy reduces allergen-mediated CD66b expression and myeloperoxidase levels on human neutrophils from allergic patients.

UNLABELLED: CD66b is a member of the carcinoembryonic antigen family, which mediates the adhesion between neutrophils and to endothelial cells. Allergen-specific immunotherapy is widely used to treat allergic diseases, and the molecular mechanisms underlying this therapy are poorly understood. The present work was undertaken to analyze A) the in vitro effect of allergens and immunotherapy on cell-surface CD66b expression of neutrophils from patients with allergic asthma and rhinitis and B) the in vivo effect of immunotherapy on cell-surface CD66b expression of neutrophils from nasal lavage fluid during the spring season. Myeloperoxidase expression and activity was also analyzed in nasal lavage fluid as a general marker of neutrophil activation. RESULTS: CD66b cell-surface expression is upregulated in vitro in response to allergens, and significantly reduced by immunotherapy (p<0.001). Myeloperoxidase activity in nasal lavage fluid was also significantly reduced by immunotherapy, as were the neutrophil cell-surface expression of CD66b and myeloperoxidase (p<0.001). Interestingly, CD66b expression was higher in neutrophils from nasal lavage fluid than those from peripheral blood, and immunotherapy reduced the number of CD66+MPO+ cells in nasal lavage fluid. Thus, immunotherapy positive effects might, at least in part, be mediated by the negative regulation of the CD66b and myeloperoxidase activity in human neutrophils.

Differences in osteogenic and apoptotic genes between osteoporotic and osteoarthritic patients.

BACKGROUND: Osteoporosis is a metabolic disorder characterized by a reduction in bone mass and deterioration in the microarchitectural structure of the bone, leading to a higher risk for spontaneous and fragility fractures.The main aim was to study the differences between human bone from osteoporotic and osteoarthritic patients about gene expression (osteogenesis and apoptosis), bone mineral density, microstructural and biomechanic parameters. METHODS: We analyzed data from 12 subjects: 6 with osteoporotic hip fracture (OP) and 6 with hip osteoarthritis (OA), as the control group. All subjects underwent medical history, analytical determinations, densitometry, histomorphometric and biochemical study. The expression of 86 genes of osteogenesis and 86 genes of apoptosis was studied in pool of bone samples from patients with OP and OA by PCR array. RESULTS: We observed that most of the genes of apoptosis and osteogenesis show a decrease in gene expression in the osteoporotic group in comparison with the osteoarthritic group. The histomorphometric study shows a lower bone quality in the group of patients with hip fractures compared to the osteoarthritic group. CONCLUSIONS: The bone tissue of osteoporotic fracture patients is more fragile than the bone of OA patients. Our results showed an osteoporotic bone with a lower capacities for differentiation and osteoblastic activity as well as a lower rate of apoptosis than osteoarthritic bone. These results are related with structural and biochemical parameters.

Study of bone mass in young daughters of women with fracture of the distal end of the radius.

The main aim was to assess whether young and healthy daughters of women with fractures of the distal end of the radius (DER) had less bone mass than the control group. In an observational study of cases and controls (1:1), the daughters of women with fractures of DER (96) were selected at the age of reaching the peak of bone mass and compared with a control group (91). All women underwent medical history, analytical determinations, and densitometry. In the case group, we found lower bone mass values at the spine and femoral neck than the control group. We also found a lower bone mass at the hips of daughters of women with 1 or more osteoporotic fractures associated with DER and at the lumbar spine in those whose mothers had densitometric osteoporosis. In conclusion, young daughters of women with fractures of DER had lower levels of bone mass density, with a possible "location-specific" occurrence based on the presence of 1 or more osteoporotic fractures associated with DER or on the presence of maternal densitometric osteoporosis.

Vertebral fractures in patients with inflammatory bowel disease compared with a healthy population: a prospective case-control study.

BACKGROUND: A prospective study was performed to compare the prevalence of morphometric vertebral fractures (MVF) between patients with inflammatory bowel disease (IBD) and healthy subjects and to identify predictive factors of fracture. METHODS: A total of 107 patients with IBD (53 with Crohn's disease and 54 with ulcerative colitis) and 51 healthy subjects participated in the study. Information about anthropometric parameters, toxins, previous fractures, and parameters related to this disease were evaluated. The index of vertebral deformity, bone mass density (BMD), and biochemical parameters were calculated. RESULTS: A total of 72 fractures were detected in 38.32% of patients with IBD, and 10 fractures were detected in 13.73% of healthy subjects; the risk of fracture in patients with IBD was higher than that in control subjects (OR, 4.03; 95% CI, 1.652-9.847; p < 0.002). We found no correlation between fracture and BMD in patients with IBD (lumbar spine, r = -0.103, p = 0.17 and femoral neck, r = -0.138, p = 0.07). Corticosteroid treatment was not associated with prevalent vertebral fractures nor with taking corticosteroids (r = 0.135, p = 0.14) or the duration for which they were taken (r = 0.08, p = 0.38), whereas this relationship was present in the controls (r = -0.365, p = 0.01). In the multivariate analysis, none of the measured parameters were significantly predictive of fracture, only to manifested IBD. Hypovitaminosis D was observed in 55.14% of patients with IBD. CONCLUSIONS: The prevalence of morphometric vertebral fractures is higher in patients with IBD than in the healthy population, without association with BMD or corticoid treatment. Simply having IBD was proven to be a predictive factor of fracture. We observed a high incidence of hypovitaminosis D in patients with IBD.

Risk factors for prediction of inadequate response to antiresorptives.

Some patients sustain fractures while on antiresorptives. Whether this represents an inadequate response (IR) to treatment or a chance event has not been elucidated. We performed a study to identify which patients are more likely to fracture while on treatment. This is a multicentric, cross-sectional study of postmenopausal women on antiresorptives for osteoporosis in 12 Spanish hospitals, classified as adequate responders (ARs) if on treatment with antiresorptives for 5 years with no incident fractures or inadequate responders (IRs) if an incident fracture occurred between 1 and 5 years on treatment. Poor compliance, secondary osteoporosis, and previous anti-osteoporosis treatment other than the assessed were exclusion criteria. Clinical, demographic, analytical, dual-energy X-ray absorptiometry (DXA) variables, and proximal femur structure analysis (ImaTx™) and structural/fractal analyses of distal radius were performed. A total of 179 women (76 IRs; mean (SD): age 68.2 (9.0) years; 103 ARs, age 68.5 (7.9) years) were included. History of prior fracture (p = 0.005), two or more falls in the previous year (p = 0.032), low lumbar spine bone mineral density (BMD) (p = 0.02), 25 hydroxyvitamin D (p = 0.017), and hip ImaTx fracture load index (p = 0.004) were associated with IR. In the logistic regression models a fracture before treatment (odds ratio [OR], 3.60; 95% confidence interval [CI], 1.47-8.82; p = 0.005) and levels of 25 hydroxyvitamin D below 20 ng/mL (OR, 3.89; 95% CI, 1.55-9.77; p = 0.004) significantly increased risk for IR, while increased ImaTx fracture load (OR, 0.96; 95% CI, 0.93-0.99; p = 0.006; per every 100 units) was protective, although the latter became not significant when all three variables were fitted into the model. Therefore, we can infer that severity of the disease, with microarchitectural and structure deterioration, as shown by previous fracture and hip analysis, and low levels of 25 hydroxy vitamin D carry higher risk of inadequate response to antiresorptives. More potent regimes should be developed and adequate supplementation implemented to solve this problem.