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.

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.

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.

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.

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.

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.

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.

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.

RANKL/OPG in primary cultures of osteoblasts from post-menopausal women. Differences between osteoporotic hip fractures and osteoarthritis.

The OPG/RANKL/RANK system is important in the balance between bone formation and resorption. We used primary human osteoblasts (hOBs) cells to examine the impact of 17-beta-estradiol (E2) or/and 1,25-dihydroxyvitamin D (1,25D) in OPG/RANKL system in 28 post-menopausal (PM) women; (a) with hip fracture (OP) or (b) with osteoarthritis (OA). The hOB from OP patients proliferated slower during the first stage, than the OA women (31.5+/-2.6 and 21.4+/-1.3 days, respectively, p<0.05). The OP group secreted significantly higher OPG protein levels than the OA women (10.1+/-2.6 and 4.4+/-0.8pmol/L, respectively, p<0.05). The 1,25D and 1,25D+E2 induce an increase in RANKL and RANKL/OPG mRNA expression in OP patients above 200% (p<0.05). HOBs from the osteoporotic hip initially proliferate slower but after reaching the first cellular confluence, the proliferation rate is equal in both groups. Furthermore, hOBs from hips with OP present a higher protein secretion of OPG, and higher RANKL and RANKL/OPG expression ratio in response to 1,25D and 1,25D+E2, than hOBs from OA women. All this could suggest that the greater bone loss that characterizes OP patients can be mediated due to differences in the secretion and expression of the RANKL/OPG system in response to different stimuli.

Large-scale analysis of association between polymorphisms in the transforming growth factor beta 1 gene (TGFB1) and osteoporosis: the GENOMOS study.

INTRODUCTION: The TGFB1 gene which encodes transforming growth factor beta 1, is a strong candidate for susceptibility to osteoporosis and several studies have reported associations between bone mineral density (BMD), osteoporotic fractures and polymorphisms of TGFB1, although these studies have yielded conflicting results. METHODS: We investigated associations between TGFB1 polymorphisms and BMD and fracture in the GENOMOS study: a prospective multicenter study involving 10 European research studies including a total of 28,924 participants. Genotyping was conducted for known TGFB1 polymorphisms at the following sites: G-1639-A (G-800-A, rs1800468), C-1348-T (C-509-T, rs1800469), T29-C (Leu10Pro, rs1982073), G74-C (Arg25Pro, rs1800471) and C788-T (Thr263Ile, rs1800472). These polymorphisms were genotyped prospectively and methodology was standardized across research centers. Genotypes and haplotypes were related to BMD at the lumbar sine and femoral neck and fractures. RESULTS: There were no significant differences in either women or men at either skeletal site for any of the examined polymorphisms with the possible exception of a weak association with reduced BMD (-12 mg/cm2) in men with the T-1348 allele (p<0.05). None of the haplotypes was associated with BMD and none of the polymorphisms or haplotypes significantly affected overall risk of fractures, however, the odds ratio for incident vertebral fracture in carriers of the rare T788 allele was 1.64 (95% CI: 1.09-2.64), p<0.05. CONCLUSIONS: This study indicates that polymorphic variation in the TGFB1 gene does not play a major role in regulating BMD or susceptibility to fractures. The weak associations we observed between the C-1348-T and lumbar spine BMD in men and between C788-T and risk of incident vertebral fractures are of interest but could be chance findings and will need replication in future studies.

[Evolution of bone mass in children and adolescents with type 1 diabetes mellitus]. / Evolución de la masa ósea durante la infancia y adolescencia en niños con diabetes mellitus tipo 1.

BACKGROUND AND OBJECTIVE: There is some controversy over bone mineral density (BMD) in children and teenagers with type 1 diabetes mellitus (DM1). We evaluated BMD by dual-energy X-ray absorptiometry (DXA) and correlated it with anthropometric, biochemical and hormonal parameters related to bone metabolism. PATIENTS AND METHOD: Sixty-six patients with DM1 (26 males and 40 females) aged between 3 and 17 years, and 327 controls with a similar age were studied. RESULTS: The BMD of all diabetic patients was not different from that of the controls. However, the subgroup of older males (between 15 and 17 years) had a significantly inferior BMD than controls of the same age: mean (standard deviation), 0.888 (0.13) versus 0.994 (0.11) (p = 0.027). BMD was inferior to -1 standard deviation (Z-score) in 21.2% of diabetic children. All the biochemical and hormonal parameters were within the normality rank. There was a negative correlation between the evolution time of the disease and the levels of 25-hydroxycholecalciferol (r = -0.345; p = 0.006). We did not observe any correlation between BMD and the remaining studied parameters. CONCLUSIONS: These results confirm that initially children and adolescents with non-complicated DM1 have no alteration of the bone mass. Yet the BMD physiological increase is smaller in the diabetic population than in controls during the adolescence period, which may cause a lower peak of bone mass in these patients.

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.

Osteocalcin in serum, saliva and gingival crevicular fluid: their relation with periodontal treatment outcome in postmenopausal women.

BACKGROUND: Osteocalcin levels have been postulated as a marker of inhibition of bone formation. The aim of the present study was to assess plasma, saliva and GCF levels of osteocalcin and correlate them with periodontal treatment outcome in postmenopausal women. METHODS: Thirty-nine postmenopausal women (57.8 -/+8.5 years old) were recruited for the study. Periodontal examination of all women was carried out and plaque, bleeding on probing, probing depth (PD), and clinical attachment level (CAL) were recorded. Serum, saliva and gingival crevicular fluid osteocalcin were measured. Then, periodontal treatment was carried out. Six months after the first appointment a second periodontal examination was carried out. RESULTS: Mean PD and mean CAL decreased significantly at second appointment in the group with serum osteocalcin concentration <10 ng/ml (15.8 -/+15.8% and 15.3 -/+ 21.2% respectively; p < 0.05). Mean PD decreased significantly at second appointment in the groups with saliva osteocalcin concentration < 3 ng/ml (17.1 -/+ 15.9%; p < 0.05) and 3-7 ng/ml (16.2 -/+18.1%; p < 0.05). CONCLUSIONS: Low serum osteocalcin concentration is associated to a significantly higher percentage of decrease in PD and CAL after periodontal treatment in postmenopausal women. Low saliva osteocalcin concentrations are significantly associated to a higher percentage of decrease in PD.

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.

Clinical and molecular epidemiology of extended-spectrum beta-lactamase-producing Escherichia coli as a cause of nosocomial infection or colonization: implications for control.

BACKGROUND: Extended-spectrum beta-lactamase (ESBL)-producing members of the Enterobacteriaceae family are important nosocomial pathogens. Escherichia coli producing a specific family of ESBL (the CTX-M enzymes) are emerging worldwide. The epidemiology of these organisms as causes of nosocomial infection is poorly understood. The aims of this study were to investigate the clinical and molecular epidemiology of nosocomial infection or colonization due to ESBL-producing E. coli in hospitalized patients, consider the specific types of ESBLs produced, and identify the risk factors for infection and colonization with these organisms. METHODS: All patients with nosocomial colonization and/or infection due to ESBL-producing E. coli in 2 centers (a tertiary care hospital and a geriatric care center) identified between January 2001 and May 2002 were included. A double case-control study was performed. The clonal relatedness of the isolates was studied by repetitive extragenic palindromic-polymerase chain reaction and pulsed-field gel electrophoresis. ESBLs were characterized by isoelectric focusing, polymerase chain reaction, and sequencing. RESULTS: Forty-seven case patients were included. CTX-M-producing E. coli were clonally unrelated and more frequently susceptible to nonoxyimino-beta-lactams. Alternately, isolates producing SHV- and TEM-type ESBL were epidemic and multidrug resistant. Urinary catheterization was a risk factor for both CTX-M-producing and SHV-TEM-producing isolates. Previous oxyimino-beta-lactam use, diabetes, and ultimately fatal or nonfatal underlying diseases were independent risk factors for infection or colonization with CTX-M-producing isolates, whereas previous fluoroquinolone use was associated with infection or colonization with SHV-TEM-producing isolates. CONCLUSIONS: The epidemiology of ESBL-producing E. coli as a cause of nosocomial infection is complex. Sporadic CTX-M-producing isolates coexisted with epidemic multidrug-resistant SHV-TEM-producing isolates. These data should be taken into account for the design of control measures.

[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.

Serum, saliva, and gingival crevicular fluid osteocalcin: their relation to periodontal status and bone mineral density in postmenopausal women.

BACKGROUND: Periodontitis and osteoporosis are characterized by the loss of bone mass. Osteocalcin levels have been postulated as a marker of inhibition of bone formation. The aim of the present study was to assess plasma, saliva, and gingival crevicular fluid (GCF) levels of osteocalcin and correlate them with periodontitis and osteoporosis. METHODS: Seventy-three postmenopausal women, over 35 years old, were recruited for the study. Serum, saliva, and GCF osteocalcin were measured. Vertebral bone mineral density was measured by dual-energy x-ray absorptiometry. Differences between groups were assessed by analysis of variance (ANOVA), chi-square test, and non-parametric Kruskal-Wallis test. RESULTS: Thirty-four (46.6%) were classified in the normal healthy bone group, 11 women (15.1%) in the osteopenic group, and 28 women (38.4%) in the osteoporotic group. No statistically significant differences between these densitometric groups were observed in probing depth (P = 0.24); clinical attachment level (P = 0.11); or mean osteocalcin concentrations in serum, saliva, and GCF. Twenty-seven (37.0%) of the women were classified without periodontitis (NPG) and 63.0% (N = 46) with periodontal disease (PG). There were no statistical differences in serum and saliva osteocalcin concentrations between these two groups. GCF osteocalcin concentrations were significantly higher in the PG women than in the NPG group (P = 0.008). Mean probing depth correlated significantly with GCF osteocalcin concentrations (r = 0.35; P = 0.002). CONCLUSION: The results further support the concept that osteocalcin levels in GCF correlates with periodontal but not with osteoporosis status.

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.

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.