Bone-Forming and Antiresorptive Effects of Romosozumab in Postmenopausal Women With Osteoporosis: Bone Histomorphometry and Microcomputed Tomography Analysis After 2 and 12 Months of Treatment

Sclerostin, a protein produced by osteocytes, inhibits bone formation. Administration of sclerostin antibody results in increased bone formation in multiple animal models. Romosozumab, a humanized sclerostin antibody, has a dual effect on bone, transiently increasing serum biochemical markers of bone formation and decreasing serum markers of bone resorption, leading to increased BMD and reduction in fracture risk in humans. We aimed to evaluate the effects of romosozumab on bone tissue. In a subset of 107 postmenopausal women with osteoporosis in the multicenter, international, randomized, double-blind, placebo-controlled Fracture Study in Postmenopausal Women with Osteoporosis (FRAME), transiliac bone biopsies were performed either after 2 (n = 34) or 12 (n = 73) months of treatment with 210 mg once monthly of romosozumab or placebo to evaluate histomorphometry and microcomputed tomography-based microarchitectural endpoints. After 2 months, compared with either baseline values assessed after a quadruple fluorochrome labeling or placebo, significant increases (P < 0.05 to P < 0.001) in dynamic parameters of formation (median MS/BS: romosozumab 1.51% and 5.64%; placebo 1.60% and 2.31% at baseline and month 2, respectively) were associated with a significant decrease compared with placebo in parameters of resorption in cancellous (median ES/BS: placebo 3.4%, romosozumab 1.8%; P = 0.022) and endocortical (median ES/BS: placebo 6.3%, romosozumab 1.6%; P = 0.003) bone. At 12 months, cancellous bone formation was significantly lower (P < 0.05 to P < 0.001) in romosozumab versus placebo and the lower values for resorption endpoints seen at month 2 persisted (P < 0.001), signaling a decrease in bone turnover (P = 0.006). No significant change was observed in periosteal and endocortical bone. This resulted in an increase in bone mass and trabecular thickness with improved trabecular connectivity, without significant modification of cortical porosity at month 12. In conclusion, romosozumab produced an early and transient increase in bone formation, but a persistent decrease in bone resorption. Antiresorptive action eventually resulted in decreased bone turnover. This effect resulted in significant increases in bone mass and improved microarchitecture.© 2019 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research (ASBMR).     

Quantitative evaluation of cerebral metabolites and cerebral blood flow in patients with carotid stenosis

Abstract

We examined the metabolic and hemodynamic status of patients with severe carotid stenosis and evaluated the effectiveness of carotid endarterectomy (CEA) by comparing pre- and post-operative results of quantitative proton magnetic resonance spectroscopy (¹H-MRS) and single-photon emission computed tomography (SPECT). Quantitative ¹H-MRS and SPECT were performed in 17 patients with severe carotid stenosis before CEA; in 10 patients the examinations were repeated after CEA. There was a significant correlation between the degree of internal carotid artery (ICA) stenosis and the N-acetyl-aspartate (NAA) concentration, and between CBF and NAA in the basal ganglia. In 10 of the 17 patients (58.8%) we noted a decrease of NAA on ¹H-MRS. After CEA in these patients, NAA was significantly increased, and in 7 of 8 patients whose pre-operative SPECT had indicated impairment of cerebral vasoreactivity, it was improved. Quantitative ¹H-MRS and CBF measurements can indicate the severity of metabolic and hemodynamic impairment in patients with severe carotid stenosis, and can help to assess the effectiveness of CEA. [Neurol Res 2001; 23: 573-580]     

早期电针治疗缺血性与出血性中风头颅CT分析

观察１００例中风急性期患者,结果表明电针对急性中风疗效肯定（显效率７６７％,有效率９７０％）。结合ＣＴ分析,中风患者病情程度及疗效与病灶性质关系不明显（Ｐ＞００５）,而与病灶大小,部位深浅有关（Ｐ＜００１）。     

计算机X线断层摄影术引导后路注射胶原酶治腰椎间盘突出症的临床疗效观察

【目的】探讨腰椎间盘突出后路联合注射胶原酶到突出物内和表面的技术与疗效。【方法】通过第5腰椎和第1骶椎间(L5-S1)解剖学和影像学的研究分析,确定经小关节内缘、穿黄韧带、通过硬膜外达突出物的穿刺入路(简称后路)。在临床应用中结合硬膜外计算机X线断层摄影术(CT)空气造影解决该入路的准确性和安全性问题。对60例经CT检查,诊断为L5-S1椎间盘突出症的患者在CT引导下后路直接注射胶原酶到突出物内和表面。【结果】穿刺成功率100％,经术后3个月至3年的随访,57例疗效优良,优良率为95％,18例3个月后经CT复查有17例突出物变小或消失,溶解率94．4％。【结论】CT引导注射胶原酶是治疗L5-S1椎间盘突出症的有效的方法之一。     

Bone attenuation on routine chest CT correlates with bone mineral density on DXA in patients with COPD

Chronic obstructive pulmonary disease (COPD), although primarily a disease of the lungs, is associated with extrapulmonary effects such as muscle weakness and osteoporosis. Fractures owing to osteoporosis cause significant morbidity and mortality, particularly in patients with COPD. To prevent osteoporotic fractures, it is important to diagnose osteoporosis in an early stage and to start anti‐osteoporotic therapy in at‐risk patients. Because routine chest computed tomography (CT) is increasingly used to assess the extent of emphysema and airways disease in patients with COPD, we investigated whether simple attenuation measurement of the thoracic spine on routine chest CT may provide useful information on bone health in patients with COPD. Fifty‐eight patients with moderate to very severe COPD were included in our study. The average attenuation of thoracic vertebrae 4, 7, and 10 on chest CT was correlated with the lowest bone mineral density (BMD) of the hip and lumbar spine (L₁ to L₄) on dual‐energy X‐ray absorptiometry (DXA) in patients with COPD. The inter‐ and intra‐observer variabilities of the attenuation measurements were low as shown by Bland‐Altman plots. Pearson's correlation coefficient between the average attenuation of the three thoracic vertebrae and the lowest BMD of the hip and lumbar spine was high (r = 0.827, p < 0.001). A receiver‐operating characteristic (ROC) analysis of the area under the curve for osteoporosis was 0.969 (p < 0.001), corresponding to an attenuation threshold of 147 Hounsfield Units (HU). In conclusion, our data demonstrated that bone attenuation measured on routine chest CT correlated strongly with BMD assessed on DXA in patients with COPD. Routine chest CT may provide useful information on bone health in patients with COPD. © 2012 American Society for Bone and Mineral Research.     

Biocompatibility of platinum-metallized silicone rubber: in vivo and in vitro evaluation

Silicone rubber is commonly used for biomedical applications, including implanted cuff electrodes for both recording and stimulation of peripheral nerves. This study was undertaken to evaluate the consequences of a new platinum metallization method on the biocompatibility of silicone rubber cuff electrodes. This method was introduced in order to allow the manufacture of spiral nerve cuff electrodes with a large number of contacts. The metallization process, implying silicone coating with poly(methyl methacrylate) (PMMA), its activation by an excimer laser and subsequent electroless metal deposition, led to a new surface microtexture. The neutral red cytotoxicity assay procedure was first applied in vitro on BALB/c 3T3 fibroblasts in order to analyze the cellular response elicited by the studied material. An in vivo assay was then performed to investigate the tissue reaction after chronic subcutaneous implantation of the metallized material. Results demonstrate that silicone rubber biocompatibility is not altered by the new platinum metallization method.     

Adenovirus 36, adiposity,and bone strength in late‐adolescent females

Adenovirus 36 (Ad36) is the only adenovirus to date that has been linked with obesity in humans. Our previous studies in late‐adolescent females suggest that excess weight in the form of fat mass is associated with lower cortical bone strength. The purpose of this study was to assess the relationship between Ad36‐specific antibodies, adiposity, and bone strength in our sample of late‐adolescent females. A cross‐sectional study of 115 females aged 18 to 19 years was performed. Participants were classified according to adiposity by dual‐energy X‐ray absorptiometry (body fat percentage as normal‐fat [ < 32% body fat; n = 93] or high‐fat [ ≥ 32% body fat; n = 22]), and according to the presence of Ad36‐specific neutralizing antibodies. Peripheral quantitative computed tomography measured bone parameters at the 4% (trabecular bone) and 20% (cortical bone) site, and muscle cross‐sectional area (MCSA) at the 66% site, from the distal metaphyses of the radius and the tibia. Bone strength was determined from volumetric bone mineral density and bone geometry to calculate bone strength index (BSI; trabecular site) and polar strength–strain index (SSI; cortical site). After adjustment for MCSA and limb length, radial SSI was lower in Ad36+ versus Ad36– subjects from the high‐fat group (p < 0.03), but not the normal‐fat group. No significant differences were observed between groups in tibial SSI or BSI. These data support an association of adiposity and cortical bone strength at the radius with the presence of neutralizing antibodies to Ad36 in late‐adolescent females. © 2013 American Society for Bone and Mineral Research.     

Temporary cerebellar hypoperfusion with good outcome in cerebellitis

Abstract

The relation between clinical outcome and single photon emission tomography (SPECT) results in cerebellitis has not been studied. A 63-year-old man developed cerebellar dysfunction with left emphasis one week after onset of cough. The only abnormality on analysis of cerebrospinal fluid was elevated protein (68 mg/dl). Magnetic resonance imaging was normal on the ninth day of ataxia. SPECT showed unilateral cerebellar hypoperfusion on the 13th day, but was normal on the 20th day. His gait improved a little by discharge on the 28th day and his tandem gait was only slightly unsteady six months later. This is the first evidence that normalization of cerebellar hypoperfusion in adult patients with cerebellitis is related to good outcome. Normalization of cerebellar hypoperfusion can occur in three weeks even when ataxia remains severe.