Glucocorticoid effects on changes in bone mineral density and cortical structure in childhood nephrotic syndrome

The impact of glucocorticoids (GC) on skeletal development has not been established. The objective of this study was to examine changes in volumetric bone mineral density (vBMD) and cortical structure over 1 year in childhood nephrotic syndrome (NS) and to identify associations with concurrent GC exposure and growth. Fifty‐six NS participants, aged 5 to 21 years, were enrolled a median of 4.3 (0.5 to 8.1) years after diagnosis. Tibia peripheral quantitative computed tomography (pQCT) scans were obtained at enrollment and 6 and 12 months later. Sex, race, and age‐specific Z‐scores were generated for trabecular vBMD (TrabBMD‐Z), cortical vBMD (CortBMD‐Z), and cortical area (CortArea‐Z) based on >650 reference participants. CortArea‐Z was further adjusted for tibia length‐for‐age Z‐score. Quasi‐least squares regression was used to identify determinants of changes in pQCT Z‐scores. At enrollment, mean TrabBMD‐Z (?0.54 ± 1.32) was significantly lower (p = 0.0001) and CortBMD‐Z (0.73 ± 1.16, p < 0.0001) and CortArea‐Z (0.27 ± 0.91, p = 0.03) significantly greater in NS versus reference participants, as previously described. Forty‐eight (86%) participants were treated with GC over the study interval (median dose 0.29 mg/kg/day). On average, TrabBMD‐Z and CortBMD‐Z did not change significantly over the study interval; however, CortArea‐Z decreased (p = 0.003). Greater GC dose (p < 0.001), lesser increases in tibia length (p < 0.001), and lesser increases in CortArea‐Z (p = 0.003) were independently associated with greater increases in CortBMD‐Z. Greater increases in tibia length were associated with greater declines in CortArea‐Z (p < 0.01); this association was absent in reference participants (interaction p < 0.02). In conclusion, GC therapy was associated with increases in CortBMD‐Z, potentially related to suppressed bone formation and greater secondary mineralization. Conversely, greater growth and expansion of CortArea‐Z (ie, new bone formation) were associated with declines in CortBMD‐Z. Greater linear growth was associated with impaired expansion of cortical area in NS. Studies are needed to determine the fracture implications of these findings. © 2013 American Society for Bone and Mineral Research.     

Bone health in children and adolescents with perinatal HIV infection

The long-term impact on bone health of lifelong HIV infection and prolonged ART in growing and developing children is not yet known. Measures of bone health in youth must be interpreted in the context of expected developmental and physiologic changes in bone mass, size, density and strength that occur from fetal through adult life. Low bone mineral density (BMD) appears to be common in perinatally HIV-infected youth, especially outside of high-income settings, but data are limited and interpretation complicated by the need for better pediatric norms. The potential negative effects of tenofovir on BMD and bone mass accrual are of particular concern as this drug may be used more widely in younger children. Emphasizing good nutrition, calcium and vitamin D sufficiency, weight-bearing exercise and avoidance of alcohol and smoking are effective and available approaches to maintain and improve bone health in all settings. More data are needed to inform therapies and monitoring for HIV-infected youth with proven bone fragility. While very limited data suggest lack of marked increase in fracture risk for youth with perinatal HIV infection, the looming concern for these children is that they may fail to attain their expected peak bone mass in early adulthood which could increase their risk for fractures and osteoporosis later in adulthood.     

Classification of ADHD and BMD patients using visual evoked potential

Objectives

Children with Bipolar Mood Disorder (BMD) and those with Attention Deficit Hyperactivity Disorder (ADHD) share many clinical signs and symptoms; therefore, achieving an accurate diagnosis is still a challenge, especially in the first interview session. The main focus of this paper is to quantitatively classify the ADHD and BMD patients using their Visual Evoke Potential (VEP) features elicited from their Electroencephalogram (EEG) signals.

Methods and materials

In this study, 36 subjects were participated including 12 healthy ones, 12 patients with ADHD and 12 ones with BMD. The age of ADHD patients was 16.92 ± 6.29 and for the BMD ones was 17.85 ± 3.68. Their scalp EEG signals in the presence of visual stimulus were recorded using 22 silver electrodes located according to the 10–20 international recording protocol. To extract their VEP, first a preprocessing step was executed to remove the power line and movement artifacts. Afterward, the wavelet denoising and synchronous averaging were applied to the preprocessed trials in order to elicit the P100 component. To obtain interpretable features from the evoked patterns, amplitude and latency were extracted and applied to the 1-Nearest Neighbor (1NN) classifier due to the locally scattered distribution of the VEP features.

Results

The evaluation was performed according to leave-one(subject)-out method and the experimental results were led to 92.85% classification accuracy which is a fairly promising achievement to distinguish the BMD, ADHD, and healthy subjects from each other.

Conclusion

From the physiological point of view, this result point out to the existence of significant difference in the neural activities of their visual system in the ADHD, BMD, and healthy subjects in response to a periodic optical stimulus.     

99Tc-MDP联合骨化三醇治疗原发性骨质疏松症的疗效观察

目的 探讨锝亚甲基二膦酸盐(99Tc-MDP)联合骨化三醇治疗原发性骨质疏松症的临床疗效.方法 将明确诊断的原发性骨质疏松症患者随机分成3组.治疗组(第1组)应用99Tc-MDP联合骨化三醇连续治疗12个月,对照组单独应用9Tc-MDP(第2组)或骨化三醇(第3组)进行治疗.观察并记录治疗前后患者的骨痛程度、骨密度值、血清骨特异性碱性磷酸酶(BALP)、骨钙素的变化情况.结果 共纳入117例患者,每组39例.3组治疗前骨痛程度、骨密度值、BALP、骨钙素均有可比性.第1组与第2组,第1组与第3组治疗后各项指标比较,第1组骨痛有效缓解率(94.9％)较第2组(74.4％)、第3组(71.8％)明显增高(P均＜0.05),骨密度明显增高[(0.699±0.083) g/cm2 vs.(0.651±0.101)~cm2,P＜ 0.05;(0.699±0.083) g/cm2 vs.(0.647±0.092) g/cm2,P＜ 0.05],BALP明显降低[(14.09±1.56)ng/ml vs.(15.54±0.83)ng/ml,P＜0.05;(14.09± 1.56)ng/ml vs.(15.65± 1.09)ng/ml,P＜0.05],骨钙素明显降低[(6.01±1.58) ng/ml vs.(6.22±1.64)ng/ml,P＜0.05;(6.01±1.58)ng/ml vs.(6.14±1.43)ng/ml,P＜0.05].结论 99Tc-MDP联合骨化三醇治疗原发性骨质疏松症疗效明显,无明显不良反应.     

六味地黄丸联合唑来膦酸治疗妇女绝经后骨质疏松的临床研究

目的探讨六味地黄丸联合唑来膦酸治疗妇女绝经后骨质疏松的临床效果。方法选取2015年6月—2017年1月广东医科大学附属医院收治的86例绝经后骨质疏松患者,随机分为对照组和治疗组,每组各43例。对照组静脉滴注唑来膦酸注射液,5 mg/次,1次/年。治疗组在此基础上口服六味地黄丸,8丸/次,3次/d。所有患者均连续治疗12个月。观察两组的临床疗效,比较两组治疗前后视觉模拟(VAS)评分、简明健康状况调查量表(SF-36)评分、腰椎1~4骨质密度(BMD)、全髋关节骨BMD、左侧股骨颈BMD、Ⅰ型原胶原氨基端前肽(PINP)、β-胶原降解产物(β-CTX)、碱性磷酸酶(ALP)、骨钙素(BGP)的变化情况。结果治疗后,对照组和治疗组的总有效率分别为79.07%、95.35%,两组比较差异有统计学意义(P0.05)。治疗后,两组VAS评分、血清PINP、β-CTX、ALP及BGP水平显著降低,SF-36评分、腰椎1~4 BMD值、全髋关节骨BMD值、左侧股骨颈BMD值显著升高,同组治疗前后比较差异有统计学意义(P0.05);治疗后,治疗组VAS评分、血清PINP、β-CTX、ALP及BGP水平低于对照组,SF-36评分、腰椎1~4 BMD值、全髋关节骨BMD值、左侧股骨颈BMD值高于对照组,两组比较差异有统计学意义(P0.05)。结论六味地黄丸联合唑来膦酸治疗妇女绝经后骨质疏松具有较好的临床疗效,可有效缓解患者疼痛症状,增加骨密度,提高生活质量,具有一定的临床推广应用价值。     

Potential Adverse Effect of Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) on Bisphosphonate Efficacy: An Exploratory Post Hoc Analysis From a Randomized Controlled Trial of Clodronate

Nonsteroidal anti-inflammatory drugs (NSAIDs) have been reported to have weak but beneficial effects on bone health, including fracture risk, but many epidemiological studies are likely confounded. We explored the relationship between NSAIDs and fracture risk in a post hoc analysis of a well-documented, randomized, placebo-controlled study of the bisphosphonate, clodronate, in which treatment reduced osteoporotic fracture risk by 23%. Concurrent medication use at baseline was used to identify those prescribed oral NSAIDs. Only verified, incident fractures were included in the analysis. A total of 1082 (20.8%) women reported use of NSAIDs at baseline. They were slightly, but significantly, younger (mean 79 versus 80 years, p = 0.004), heavier (mean 66.7 versus 64.7 kg, p < 0.001) than nonusers, with slightly higher femoral neck bone mineral density (FN-BMD, 0.66 versus 0.64 g/cm², p < 0.001). In an adjusted model, NSAID use was associated with a significant increase in osteoporotic fracture risk over the 3-year study period (hazard ratio [HR] 1.27; 95% confidence interval [CI], 1.01–1.62; p = 0.039). However, this increase in risk was not statistically significant in the placebo group (HR 1.11; 95% CI, 0.81–1.52). In women receiving clodronate, the effect of the bisphosphonate to reduce osteoporotic fracture risk was not observed in those receiving NSAIDs (HR 0.95; 95% CI, 0.65–1.41; p = 0.81) in contrast to those not using NSAIDs (HR 0.71; 95% CI, 0.58–0.89; p = 0.002). In a subset with hip BMD repeated at 3 years, BMD loss during clodronate therapy was greater in those women receiving NSAIDs than in nonusers (eg, total hip −2.75% versus −1.27%, p = 0.078; femoral neck −3.06% versus −1.12%, p = 0.028), and was not significantly different from that observed in women receiving placebo. The efficacy of the bisphosphonate, clodronate, to reduce fracture risk was largely negated in those receiving NSAIDs. Although the mechanism is unclear, this clinically significant observation requires exploration in studies of commonly used bisphosphonates. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).     

北京市中老年女性月经及身体成分与骨密度的相关性研究

目的调查北京市中老年女性年龄、月经和身体成分特征,分析其与骨密度的关系以及对骨密度的影响。方法招募45～80岁女性384名,调查受试者月经状况,包括初潮年龄、绝经年龄和绝经年限;测试受试者腰椎、左股骨颈、左髋以及全身骨密度,并测试全身脂肪和肌肉含量,由此计算脂肪含量指数(fat mass index,FMI)、肌肉含量指数(lean mass index,LMI)和四肢骨骼质量指数(appendicular skeletal muscle mass index,ASMI)。采用Pearson相关和多元逐步回归模型分析各因素与骨密度的关系。结果相关性结果显示,年龄、绝经年限、初潮年龄与骨密度呈显著负相关,绝经年龄、LMI、FMI和ASMI与骨密度呈显著正相关。多元逐步回归分析结果显示,绝经年限与各部位骨密度均呈显著负相关,ASMI与各部位骨密度均呈显著正相关,FMI仅与全髋和全身骨密度具有显著相关性,初潮年龄和绝经年龄仅与腰椎和全身骨密度具有显著相关性。结论绝经年限是中老年女性骨密度的独立危险因素,而ASMI则为独立保护因素,绝经年龄、初潮年龄以及FMI对中老年女性骨密度的影响存在部位差异性。     

Effects of Odanacatib on the Radius and Tibia of Postmenopausal Women: Improvements in Bone Geometry,Microarchitecture, and Estimated Bone Strength

The cathepsin K inhibitor odanacatib (ODN), currently in phase 3 development for postmenopausal osteoporosis, has a novel mechanism of action that reduces bone resorption while maintaining bone formation. In phase 2 studies, odanacatib increased areal bone mineral density (aBMD) at the lumbar spine and total hip progressively over 5 years. To determine the effects of ODN on cortical and trabecular bone and estimate changes in bone strength, we conducted a randomized, double‐blind, placebo‐controlled trial, using both quantitative computed tomography (QCT) and high‐resolution peripheral (HR‐p)QCT. In previously published results, odanacatib was superior to placebo with respect to increases in trabecular volumetric BMD (vBMD) and estimated compressive strength at the spine, and integral and trabecular vBMD and estimated strength at the hip. Here, we report the results of HR‐pQCT assessment. A total of 214 postmenopausal women (mean age 64.0 ± 6.8 years and baseline lumbar spine T‐score –1.81 ± 0.83) were randomized to oral ODN 50 mg or placebo, weekly for 2 years. With ODN, significant increases from baseline in total vBMD occurred at the distal radius and tibia. Treatment differences from placebo were also significant (3.84% and 2.63% for radius and tibia, respectively). At both sites, significant differences from placebo were also found in trabecular vBMD, cortical vBMD, cortical thickness, cortical area, and strength (failure load) estimated using finite element analysis of HR‐pQCT scans (treatment differences at radius and tibia = 2.64% and 2.66%). At the distal radius, odanacatib significantly improved trabecular thickness and bone volume/total volume (BV/TV) versus placebo. At a more proximal radial site, odanacatib attenuated the increase in cortical porosity found with placebo (treatment difference = –7.7%, p = 0.066). At the distal tibia, odanacatib significantly improved trabecular number, separation, and BV/TV versus placebo. Safety and tolerability were similar between treatment groups. In conclusion, odanacatib increased cortical and trabecular density, cortical thickness, aspects of trabecular microarchitecture, and estimated strength at the distal radius and distal tibia compared with placebo. © 2014 American Society for Bone and Mineral Research