Effects of zoledronate versus placebo on spine bone mineral density and microarchitecture assessed by the trabecular bone score in postmenopausal women with osteoporosis: A three-year study.

The trabecular bone score (TBS) is an index of bone microarchitectural texture calculated from anteroposterior dual-energy X-ray absorptiometry (DXA) scans of the lumbar spine (LS) that predicts fracture risk, independent of bone mineral density (BMD). The aim of this study was to compare the effects of yearly intravenous zoledronate (ZOL) versus placebo (PLB) on LS BMD and TBS in postmenopausal women with osteoporosis. Changes in TBS were assessed in the subset of 107 patients recruited at the Department of Osteoporosis of the University Hospital of Berne, Switzerland, who were included in the HORIZON trial. All subjects received adequate calcium and vitamin D3. In these patients randomly assigned to either ZOL (n = 54) or PLB (n = 53) for 3 years, BMD was measured by DXA and TBS assessed by TBS iNsight (v1.9) at baseline and 6, 12, 24, and 36 months after treatment initiation. Baseline characteristics (mean ± SD) were similar between groups in terms of age, 76.8 ± 5.0 years; body mass index (BMI), 24.5 ± 3.6 kg/m(2) ; TBS, 1.178 ± 0.1 but for LS T-score (ZOL-2.9 ± 1.5 versus PLB-2.1 ± 1.5). Changes in LS BMD were significantly greater with ZOL than with PLB at all time points (p < 0.0001 for all), reaching +9.58% versus +1.38% at month 36. Change in TBS was significantly greater with ZOL than with PLB as of month 24, reaching +1.41 versus-0.49% at month 36; p = 0.031, respectively. LS BMD and TBS were weakly correlated (r = 0.20) and there were no correlations between changes in BMD and TBS from baseline at any visit. In postmenopausal women with osteoporosis, once-yearly intravenous ZOL therapy significantly increased LS BMD relative to PLB over 3 years and TBS as of 2 years. © 2013 American Society for Bone and Mineral Research.

Spine bone texture assessed by trabecular bone score (TBS) predicts osteoporotic fractures in men: The Manitoba Bone Density Program.

INTRODUCTION: One quarter of osteoporotic fractures occur in men. TBS, a gray-level measurement derived from lumbar spine DXA image texture, is related to microarchitecture and fracture risk independently of BMD. Previous studies reported the ability of spine TBS to predict osteoporotic fractures in women. Our aim was to evaluate the ability of TBS to predict clinical osteoporotic fractures in men. METHODS: 3620 men aged ≥50 (mean 67.6years) at the time of baseline DXA (femoral neck, spine) were identified from a database (Province of Manitoba, Canada). Health service records were assessed for the presence of non-traumatic osteoporotic fracture after BMD testing. Lumbar spine TBS was derived from spine DXA blinded to clinical parameters and outcomes. We used Cox proportional hazard regression to analyze time to first fracture adjusted for clinical risk factors (FRAX without BMD), osteoporosis treatment and BMD (hip or spine). RESULTS: Mean followup was 4.5years. 183 (5.1%) men sustain major osteoporotic fractures (MOF), 91 (2.5%) clinical vertebral fractures (CVF), and 46 (1.3%) hip fractures (HF). Correlation between spine BMD and spine TBS was modest (r=0.31), less than correlation between spine and hip BMD (r=0.63). Significantly lower spine TBS were found in fracture versus non-fracture men for MOF (p<0.001), HF (p<0.001) and CVF (p=0.003). Area under the receiver operating characteristic curve (AUC) for incident fracture discrimination with TBS was significantly better than chance (MOF AUC=0.59, p<0.001; HF AUC=0.67, p<0.001; CVF AUC=0.57, p=0.032). TBS predicted MOF and HF (but not CVF) in models adjusted for FRAX without BMD and osteoporosis treatment. TBS remained a predictor of HF (but not MOF) after further adjustment for hip BMD or spine BMD. CONCLUSION: We observed that spine TBS predicted MOF and HF independently of the clinical FRAX score, HF independently of FRAX and BMD in men. Studies with more incident fractures are needed to confirm these findings.

Neural substrates of social emotion regulation: a FMRI study on imitation and expressive suppression to dynamic facial signals.

Emotion regulation is crucial for successfully engaging in social interactions. Yet, little is known about the neural mechanisms controlling behavioral responses to emotional expressions perceived in the face of other people, which constitute a key element of interpersonal communication. Here, we investigated brain systems involved in social emotion perception and regulation, using functional magnetic resonance imaging (fMRI) in 20 healthy participants. The latter saw dynamic facial expressions of either happiness or sadness, and were asked to either imitate the expression or to suppress any expression on their own face (in addition to a gender judgment control task). fMRI results revealed higher activity in regions associated with emotion (e.g., the insula), motor function (e.g., motor cortex), and theory of mind (e.g., [pre]cuneus) during imitation. Activity in dorsal cingulate cortex was also increased during imitation, possibly reflecting greater action monitoring or conflict with own feeling states. In addition, premotor regions were more strongly activated during both imitation and suppression, suggesting a recruitment of motor control for both the production and inhibition of emotion expressions. Expressive suppression (eSUP) produced increases in dorsolateral and lateral prefrontal cortex typically related to cognitive control. These results suggest that voluntary imitation and eSUP modulate brain responses to emotional signals perceived from faces, by up- and down-regulating activity in distributed subcortical and cortical networks that are particularly involved in emotion, action monitoring, and cognitive control.

Spine trabecular bone score subsequent to bone mineral density improves fracture discrimination in women.

Bone mineral density (BMD) measured by dual-energy X-ray absorptiometry (DXA) is used to diagnose osteoporosis and assess fracture risk. However, DXA cannot evaluate trabecular microarchitecture. This study used a novel software program (TBS iNsight; Med-Imaps, Geneva, Switzerland) to estimate bone texture (trabecular bone score [TBS]) from standard spine DXA images. We hypothesized that TBS assessment would differentiate women with low trauma fracture from those without. In this study, TBS was performed blinded to fracture status on existing research DXA lumbar spine (LS) images from 429 women. Mean participant age was 71.3 yr, and 158 had prior fractures. The correlation between LS BMD and TBS was low (r = 0.28), suggesting these parameters reflect different bone properties. Age- and body mass index-adjusted odds ratios (ORs) ranged from 1.36 to 1.63 for LS or hip BMD in discriminating women with low trauma nonvertebral and vertebral fractures. TBS demonstrated ORs from 2.46 to 2.49 for these respective fractures; these remained significant after lowest BMD T-score adjustment (OR = 2.38 and 2.44). Seventy-three percent of all fractures occurred in women without osteoporosis (BMD T-score > -2.5); 72% of these women had a TBS score below the median, thereby appropriately classified them as being at increased risk. In conclusion, TBS assessment enhances DXA by evaluating trabecular pattern and identifying individuals with vertebral or low trauma fracture. TBS identifies 66-70% of women with fracture who were not classified with osteoporosis by BMD alone.

The Selective Phosphodiesterase 4 Inhibitor Roflumilast and Phosphodiesterase 3/4 Inhibitor Pumafentrine Reduce Clinical Score and TNF Expression in Experimental Colitis in Mice.

OBJECTIVE: The specific inhibition of phosphodiesterase (PDE)4 and dual inhibition of PDE3 and PDE4 has been shown to decrease inflammation by suppression of pro-inflammatory cytokine synthesis. We examined the effect of roflumilast, a selective PDE4 inhibitor marketed for severe COPD, and the investigational compound pumafentrine, a dual PDE3/PDE4 inhibitor, in the preventive dextran sodium sulfate (DSS)-induced colitis model. METHODS: The clinical score, colon length, histologic score and colon cytokine production from mice with DSS-induced colitis (3.5% DSS in drinking water for 11 days) receiving either roflumilast (1 or 5 mg/kg body weight/d p.o.) or pumafentrine (1.5 or 5 mg/kg/d p.o.) were determined and compared to vehicle treated control mice. In the pumafentrine-treated animals, splenocytes were analyzed for interferon-γ (IFNγ) production and CD69 expression. RESULTS: Roflumilast treatment resulted in dose-dependent improvements of clinical score (weight loss, stool consistency and bleeding), colon length, and local tumor necrosis factor-α (TNFα) production in the colonic tissue. These findings, however, were not associated with an improvement of the histologic score. Administration of pumafentrine at 5 mg/kg/d alleviated the clinical score, the colon length shortening, and local TNFα production. In vitro stimulated splenocytes after in vivo treatment with pumafentrine showed a significantly lower state of activation and production of IFNγ compared to no treatment in vivo. CONCLUSIONS: These series of experiments document the ameliorating effect of roflumilast and pumafentrine on the clinical score and TNF expression of experimental colitis in mice.

Effects of anti-resorptive agents on trabecular bone score (TBS) in older women.

We evaluated the longitudinal effects of anti-resorptive agents (534 treated women vs. 1,150 untreated) on lumbar spine bone mineral density (BMD) and trabecular bone score (TBS). TBS was responsive to treatment in women over age 50. The treatment-related increase in TBS was less than the increase in BMD, which is consistent with bone texture preservation. INTRODUCTION: In addition to inducing an increase in BMD, anti-resorptive agents also help to preserve bone architecture. TBS, a new gray-level texture measurement, correlates with 3D parameters of bone micro-architecture independent of BMD. Our objective was to evaluate the longitudinal effects of anti-resorptive agents on lumbar spine BMD and TBS. METHODS: Women (≥50 years), from the BMD program database for the province of Manitoba, Canada, who had not received any anti-resorptive drug prior to their initial dual X-ray absorptiometry (DXA) exam were divided into two groups: untreated, those without any anti-resorptive drug over the course of follow-up, and treated, those with a non-estrogen anti-resorptive drug (86 % bisphosphonates, 10 % raloxifene, and 4 % calcitonin). Lumbar spine TBS was calculated for each lumbar spine DXA examination. Changes in TBS and BMD between baseline and follow-up (mean follow-up 3.7 years), expressed in percentage per year, were compared between the two groups. RESULTS: A total of 1,150 untreated women and 534 treated women met the inclusion criteria. Only a weak correlation was seen between BMD and TBS in either group. Significant intergroup differences in BMD change and TBS change were observed over the course of follow-up (p < 0.001). Similar mean decreases in BMD and TBS (-0.36 %/year and -0.31 %/year, respectively) were seen for untreated subjects (both p < 0.001). Conversely, treated subjects exhibited a significant mean increase in BMD (+1.86 %/year, p < 0.002) and TBS (+0.20 %/year, p < 0.001). CONCLUSION: TBS is responsive to treatment with non-estrogen anti-resorptive drug therapy in women over age 50. The treatment-related increase in TBS is less than the increase in BMD, which is consistent with bone texture preservation.

TBS (Trabecular Bone Score) is More Sensitive Than BMD to Diabetes-Related Fracture Risk

Background:Type 2 diabetes (T2D) is associated with increased fracture risk but paradoxically greater BMD. TBS (trabecular bone score), a novel grey-level texture measurement extracted from DXA images, correlates with 3D parameters of bone micro-architecture. We evaluated the ability of lumbar spine (LS) TBS to account for the increased fracture risk in diabetes. Methods:29,407 women ≥50 years at the time of baseline hip and spine DXA were identified from a database containing all clinical BMD results for the Province of Manitoba, Canada. 2,356 of the women satisfied a well-validated definition for diabetes, the vast majority of whom (>90%) would have T2D. LS L14 TBS was derived for each spine DXA examination blinded to clinical parameters and outcomes. Health service records were assessed for incident non-traumatic major osteoporotic fracture codes (mean follow-up 4.7 years). Results:In linear regression adjusted for FRAX risk factors (age,BMI, glucocorticoids, prior major fracture, rheumatoid arthritis, COPD as a smoking proxy, alcohol abuse) and osteoporosis therapy, diabetes was associated with higher BMD for LS, femoral neck and total hip but lower LS TBS (all p<0.001). Similar results were seen after excluding obese subjects withBMI>30. In logistic regression (Figure), the adjusted odds ratio (OR) for a skeletal measurement in the lowest vs highest tertile was less than 1 for all BMD measurements but increased for LS TBS (adjusted OR 2.61, 95%CI 2.30-2.97). Major osteoporotic fractures were identified in 175 (7.4%) with and 1,493 (5.5%) without diabetes (p < 0.001). LS TBS predicted fractures in those with diabetes (adjusted HR 1.27, 95%CI 1.10-1.46) and without diabetes (HR 1.31, 95%CI 1.24-1.38). LS TBS was an independent predictor of fracture (p<0.05) when further adjusted for BMD (LS, femoral neck or total hip). The explanatory effect of diabetes in the fracture prediction model was greatly reduced when LS TBS was added to the model (indicating that TBS captured a large portion of the diabetes-associated risk), but was paradoxically increased from adding any of the BMD measurements. Conclusions:Lumbar spine TBS is sensitive to skeletal deterioration in postmenopausal women with diabetes, whereas BMD is paradoxically greater. LS TBS predicts osteoporotic fractures in those with diabetes, and captures a large portion of the diabetes-associated fracture risk. Combining LS TBS with BMD incrementally improves fracture prediction.

Birth weight, weight change, and blood pressure during childhood and adolescence: a school-based multiple cohort study.

OBJECTIVE: We assessed the association between birth weight, weight change, and current blood pressure (BP) across the entire age-span of childhood and adolescence in large school-based cohorts in the Seychelles, an island state in the African region. METHODS: Three cohorts were analyzed: 1004 children examined at age 5.5 and 9.1 years, 1886 children at 9.1 and 12.5, and 1575 children at 12.5 and 15.5, respectively. Birth and 1-year anthropometric data were gathered from medical files. The outcome was BP at age 5.5, 9.1, 12.5 or 15.5 years, respectively. Conditional linear regression analysis was used to estimate the relative contribution of changes in weight (expressed in z-score) during different age periods on BP. All analyses were adjusted for height. RESULTS: At all ages, current BP was strongly associated with current weight. Birth weight was not significantly associated with current BP. Upon adjustment for current weight, the association between birth weight and current BP tended to become negative. Conditional linear regression analyses indicated that changes in weight during successive age periods since birth contributed substantially to current BP at all ages. The strength of the association between weight change and current BP increased throughout successive age periods. CONCLUSION: Weight changes during any age period since birth have substantial impact on BP during childhood and adolescence, with BP being more responsive to recent than earlier weight changes.

Suspicion d'hémorragie sous-arachnoïdienne: place d'un score prédictif dans la stratégie diagnostique actuelle [Usefulness of a predictive score in subarachnoid hemorrhage diagnosis].

Usefulness of a predictive score in subarachnoid hemorrhage diagnosis Nearly half of the patients with non-traumatic subarachnoid hemorrhage (SAH) present with no neurological signs, inducing clinical underestimation of the gravity of their affection. As the outcome of aneurismal SAH is highly dependant on the initial neurological status and the recurrence of untreated hemorrhagic events, these neurologically intact patients stand to suffer the most from delayed diagnosis. Although there is currently no validated predictive score that reliably identifies SAH-induced headache, a combination of clinical criteria derived from a cohort of sudden-onset headache patients should allow risk stratification and identification of those patients requiring further investigation.