Serum nuclear factor IB as a novel and noninvasive indicator in the diagnosis of secondary hyperparathyroidism

BackgroundChronic renal failure (CRF) referred to chronic progressive renal parenchymal damage caused by various causes, with metabolite retention and imbalance of water, electrolyte, and acid‐base balance as the main clinical manifestations. Secondary hyperparathyroidism (sHPT) was a common complication in maintenance hemodialysis patients with CRF. Nuclear factor IB (NFIB) was a newly found tumor suppressor gene in various cancers. The present study aimed to illustrate the role of NFIB in sHPT clinical diagnosis and treatment response.MethodsA retrospective, case‐control study, including 189 patients with sHPT and 106 CRF patients without sHPT, compared with 95 controls. Serum NFIB and 1,25(OH)₂D₃ levels were measured by RT‐qPCR and ELISAs, respectively. ROC analysis was conducted to verify the diagnostic value of NFIB in sHPT. Spearman''s correlation analysis was conducted to verify the association between NFIB and bone mineral density (BMD) scores. After 6 months of treatment, the variance of NFIB and 1,25(OH)₂D₃ in different groups was recorded.ResultsThe expression of NFIB was significantly lower in serum samples from sHPT and non‐sHPT CRF patients, compared to controls. Clinicopathological information verified sHPT was associated with NFIB, parathyroid hormone (PTH), serum calcium, serum phosphorus, time of dialysis, and serum 1,25(OH)₂D₃ levels. Spearman''s correlation analysis illustrated the positive correlation between NFIB levels and BMD scores. At receiver operator characteristic (ROC) curve analysis, the cutoff of 1.6508 for NFIB was able to identify patients with sHPT from healthy controls; meanwhile, NFIB could also discriminate sHPT among CRF patients as well (cutoff = 1.4741). Furthermore, we found that during 6 months of treatment, NFIB levels were gradually increased, while PTH and serum P levels were decreased.ConclusionsSerum NFIB was a highly accurate tool to identify sHPT from healthy controls and CRF patients. Due to its simplicity, specificity, and sensitivity, this candidate can be proposed as a first‐line examination in the diagnostic workup in sHPT.     

Diuretic-induced hyponatremia and osteoporotic fractures in patients admitted to the emergency department

Objective

Hyponatremia is a complication of diuretic treatment and has been recently identified as a novel factor associated with osteoporosis and fractures. The impact of diuretic-associated electrolyte disorders on osteoporotic fractures (OF) has rarely been studied systematically.

Design and setting

We conducted a study in patients presenting to the emergency department at the University Hospital Bern. In this retrospective case series analysis of prospectively gathered data, over a 2-year period we identified 10,823 adult (≥50 years) outpatients with a measured baseline serum sodium, at admission to the hospital. OF patients were compared to a control group without fractures using standard statistical methods.

Results

Four hundred and eighty (5%) patients had 547 OF. The OF group had a higher mean age (73 vs. 68 years, p < 0.0001), smaller proportion of men (37% vs. 58%, p < 0.0001), higher hospitalisation rate (83% vs. 62%, p < 0.0001) and longer hospital stay (8 vs. 6 days, p < 0.0001). Any diuretic agent (p < 0.0001), loop diurietics (p = 0.02), spironolactone (p = 0.02) and amiloride (p < 0.01) were used significantly more in OF patients, but not thiazides (p = 0.68). The prevalence of hyponatremia increased significantly (p < 0.0001) with the number of diuretics taken. Advanced age (odds ratio [OR] 1.04, p < 0.0001), hyponatremia (OR 1.46, p = 0.011) higher serum creatinine (OR 1.53, p = 0.0001), furosemide use alone (OR 1.40, p = 0.01) and co-treatment with amiloride (OR 2.22, p = 0.02) were associated with a higher risk for OF.

Conclusions

This study highlights the clinical association of hyponatremia during the use of certain diuretics (i.e. furosemide or in combination, i.e. amiloride) with an increased risk of osteoporosis associated fractures. Although evidence-based data is currently lacking a pragmatic approach concerning hyponatremia monitoring and correction appears reasonable in selected groups of patients.     

Associations of 25‐Hydroxyvitamin D and 1,25‐Dihydroxyvitamin D With Bone Mineral Density,Bone Mineral Density Change,and Incident Nonvertebral Fracture

Relationships between 1,25‐dihydroxyvitamin D (1,25(OH)₂D) and skeletal outcomes are uncertain. We examined the associations of 1,25(OH)₂D with bone mineral density (BMD), BMD change, and incident non‐vertebral fractures in a cohort of older men and compared them with those of 25‐hydroxyvitamin D (25OHD). The study population included 1000 men (aged 74.6 ± 6.2 years) in the Osteoporotic Fractures in Men (MrOS) study, of which 537 men had longitudinal dual‐energy X‐ray absorptiometry (DXA) data (4.5 years of follow‐up). A case‐cohort design and Cox proportional hazards models were used to test the association between vitamin D metabolite levels and incident nonvertebral and hip fractures. Linear regression models were used to estimate the association between vitamin D measures and baseline BMD and BMD change. Interactions between 25OHD and 1,25(OH)₂D were tested for each outcome. Over an average follow‐up of 5.1 years, 432 men experienced incident nonvertebral fractures, including 81 hip fractures. Higher 25OHD was associated with higher baseline BMD, slower BMD loss, and lower hip fracture risk. Conversely, men with higher 1,25(OH)₂D had lower baseline BMD. 1,25(OH)₂D was not associated with BMD loss or nonvertebral fracture. Compared with higher levels of calcitriol, the risk of hip fracture was higher in men with the lowest 1,25(OH)₂D levels (8.70 to 51.60 pg/mL) after adjustment for baseline hip BMD (hazard ratio [HR] = 1.99, 95% confidence interval [CI] 1.19–3.33). Adjustment of 1,25(OH)₂D data for 25OHD (and vice versa) had little effect on the associations observed but did attenuate the hip fracture association of both vitamin D metabolites. In older men, higher 1,25(OH)₂D was associated with lower baseline BMD but was not related to the rate of bone loss or nonvertebral fracture risk. However, with BMD adjustment, a protective association for hip fracture was found with higher 1,25(OH)₂D. The associations of 25OHD with skeletal outcomes were generally stronger than those for 1,25(OH)₂D. These results do not support the hypothesis that measures of 1,25(OH)₂D improve the ability to predict adverse skeletal outcomes when 25OHD measures are available. © 2015 American Society for Bone and Mineral Research.     

Bone mineral density improvement after lung volume reduction surgery for severe emphysema

BACKGROUND: In patients with severe emphysema, bone mineral density (BMD) is reduced and the risk of osteoporosis is increased. STUDY OBJECTIVES: To identify the impact of lung volume reduction surgery on BMD. DESIGN: Prospective cohort study. SETTING: University hospital. PATIENTS AND INTERVENTIONS: Forty emphysematous patients, all receiving oral steroid therapy, underwent bilateral lung volume reduction surgery. Thirty similar patients, who refused the operation, followed a standard respiratory rehabilitation program. MEASUREMENTS: All subjects were evaluated pretreatment and 12 months posttreatment for respiratory function, nutritional status, and bone-related biochemical parameters. BMD was assessed by dual-energy radiograph absorptiometry. RESULTS: After surgery, we observed significant improvements in respiratory function (FEV1, + 18.8% [p < 0.01]; residual volume [RV], -29.6% [p < 0.001]; diffusing capacity of the lung for carbon monoxide [Dlco], + 21.6% [p < 0.01]) nutritional parameters (fat-free mass, + 6.0% [p < 0.01]), levels of bone-related hormones (free-testosterone, + 20.5% [p < 0.01]; parathormone, -11.2% [p < 0.01]), bone turnover markers (osteocalcin, -12.7% [p < 0.05]; bone-alkaline-phosphatase, -14.0% [p < 0.05]; beta-crosslaps, -33.6% [p < 0.001]), BMD (lumbar, + 8.8% [p < 0.01]; femoral, + 5.5% [p < 0.01]), and T-score (lumbar, + 21.0% [p < 0.01]; femoral, + 12.4% [p < 0.01]) with reduction in osteoporosis rate (50 to 25%). Nineteen patients who had undergone surgery were able to discontinue treatment with oral steroids. These subjects showed a more significant improvement in BMD (lumbar, + 9.6%; femoral, + 6.8%; p < 0.001) and T-score (lumbar, + 27.3%; femoral, + 14.3%; p < 0.001). The remaining 21 patients who had undergone surgery experienced significant improvement compared to respiratory rehabilitation subjects despite continued therapy with oral steroids (BMD: lumbar, + 4.5% vs -0.7%, respectively [p < 0.01]; femoral, + 2.7% vs -1.1%, respectively [p < 0.05]; T-score: lumbar, + 14 vs -2.1, respectively [p < 0.01]; femoral, + 7.4 vs -2.7, respectively [p < 0.01]). The increase in lumbar BMD was correlated with the surgical reduction of RV (p = 0.02) and with the increase in Dlco (p = 0.01) and fat-free mass (p = 0.01). CONCLUSIONS: Lung volume reduction surgery significantly improves BMD compared to respiratory rehabilitation therapy, even in patients requiring oral steroids. The increase in BMD correlates with RV, Dlco, and fat-free mass, suggesting that the restoration of respiratory dynamics, gas exchange, and nutritional status induces improvement in bone metabolism and mineral content.     

抗骨质疏松治疗的最佳他汀类药物及剂量选择的动物试验研究

【】 目的 探索具有最佳抗骨质疏松作用的他汀药物种类和药物剂量,为进一步的研究他汀药物同时发挥抗骨质疏松和调脂作用提供基础。 方法 40只12月龄新西兰白兔通过双侧卵巢切除和泼尼松龙诱导8周建立骨质疏松症模型,随机分为4组：生理盐水(NS)组,瑞舒伐他汀(RSV)组,辛伐他汀(Sim)组,阿仑膦酸钠片(ALN)组。RSV组和Sim组按药物剂量梯度20、40、60、80、100(mg/kg.d)分为5小组。在第0、8、12、24、36周末测量白兔股骨骨密度(BMD)和骨钙素(BGP)、抗酒石酸酸性磷酸酶5b(TRACP-5b)值。 结果 8周末白兔BMD较0周时明显降低(P＜0.05)。RSV组、Sim组比NS组BMD、BGP水平明显升高,TRACP-5b水平显著降低(P＜0.01),并且RSV组与ALN组指标水平接近(P＞0.05)。RSV组内中以60mg/kg.d喂养时,BMD、BGP较其他组明显升高。结论 他汀类药物具有抗骨质疏松的作用,效果接近唑来膦酸;亲水性瑞舒伐他汀比疏水性他汀药物更有作用;并且剂量在60mg/kg.d时效果更好。     

伊班膦酸钠联合骨化三醇治疗老年骨质疏松症的临床研究

目的 探讨伊班膦酸钠注射液联合骨化三醇胶丸治疗老年骨质疏松症的临床疗效。方法 选取2016年11月-2017年12月在上海市第三康复医院和第二军医大学附属公利医院收治的123例老年骨质疏松症患者作为研究对象,将患者随机分为骨化三醇组、伊班膦酸钠组、联合组,每组各41例。骨化三醇组患者口服骨化三醇胶丸,2粒/次,1次/d;伊班膦酸钠组患者静脉滴注伊班膦酸钠注射液,2 mg溶于0.9%氯化钠溶液250 mL中,滴注时间大于2 h,1次/3个月;联合组给予伊班膦酸钠注射液联合骨化三醇胶丸,用法用量同上。3组患者均连续治疗12个月。观察3组患者的临床疗效,比较3组患者治疗前后的数字疼痛评分（NRS）、骨密度（BMD）、血磷、血钙、抗酒石酸酸性磷酸酶5b（TRAP-5b）、骨源性碱性磷酸酶（BALP）水平和不良反应。结果 治疗后,骨化三醇组、伊班膦酸钠组、联合组的总有效率分别为82.93%、85.37%和95.12%,联合组总有效率显著优于骨化三醇组和伊班膦酸钠组,差异具有统计学意义（P<0.05）。治疗6、12个月后,3组患者的NRS评分值均显著降低,平均腰椎BMD和平均股骨颈BMD均显著升高,同组治疗前后比较差异具有统计学意义（P<0.05）;治疗6、12个月后,联合组患者的NRS评分值显著低于同期骨化三醇组和伊班膦酸钠组,而平均腰椎BMD和平均股骨颈BMD均明显高于同期骨化三醇组和伊班膦酸钠组,差异具有统计学意义（P<0.05）。治疗后,3组患者血钙、血磷相较于治疗前差异无统计学意义,且联合组患者的血钙、血磷较其他两组差异均无统计学意义。治疗6、12个月后,3组患者TRAP-5b、BALP水平均显著降低,同组治疗前后比较差异具有统计学意义（P<0.05）;治疗6、12个月后,联合组患者TRAP-5b、BALP水平显著低于同期骨化三醇组和伊班膦酸钠组,差异具有统计学意义（P<0.05）。3组患者的不良反应发生情况差异无统计学意义。结论 伊班膦酸钠注射液联合骨化三醇胶丸治疗老年性骨质疏松症具有较好的临床疗效,能够改善骨密度,减少疼痛,维持骨生化指标,具有一定的临床推广应用价值。     

骨力胶囊联合鲑降钙素治疗老年骨质疏松症的临床研究

目的探讨骨力胶囊联合鲑降钙素注射液治疗老年骨质疏松症的临床疗效。方法选取2016年3月—2018年3月三六三医院收治的骨质疏松症患者94例为研究对象,根据入院号的奇偶数分为对照组和治疗组,每组各47例。对照组皮下注射鲑降钙素注射液,50 IU/次,1次/d;治疗组在对照组治疗的基础上口服骨力胶囊,0.9 g/次,3次/d。两组均治疗8周。观察两组的临床疗效,比较两组的骨密度(BMD)、骨代谢指标、视觉模拟评分法(VAS)评分、Oswestry功能障碍指数问卷表(ODI)评分。结果治疗后,对照组和治疗组的总有效率分别为80.85%、95.74%,两组比较差异有统计学意义(P0.05)。治疗后,两组腰椎、股骨颈、股骨粗隆的BMD都明显增高,同组治疗前后比较差异有统计学意义(P0.05);且治疗组腰椎、股骨颈、股骨粗隆的BMD明显高于对照组,两组比较差异有统计学意义(P0.05)。治疗后,两组血清β-胶原降解产物(β-CTX)、抗酒石酸酸性磷酸酶(TRACP)、骨碱性磷酸酶(BNALP)水平均显著下降,骨钙素(BGP)、25-羟维生素D[25-(OH)D]水平均显著增加,同组治疗前后比较差异有统计学意义(P0.05);且治疗组血清骨代谢指标水平明显优于对照组,两组比较差异有统计学意义(P0.05)。治疗后,两组VAS评分、ODI评分均显著降低,同组治疗前后比较差异有统计学意义(P0.05);且治疗后治疗组VAS评分、ODI评分明显低于对照组,两组比较差异有统计学意义(P0.05)。结论骨力胶囊联合鲑降钙素注射液治疗老年骨质疏松症具有较好的临床疗效,可缓解疼痛,增加BMD,改善骨代谢指标,具有一定的临床推广应用价值。     

二甲双胍和辛伐他汀联用药对糖尿病大鼠骨密度变化的实验研究

目的 建立糖尿病大鼠动物模型,观察使用二甲双胍和辛伐他汀对胫骨骨密度的影响,为临床糖尿病患者种植体修复、正畸治疗提供理论依据.方法 采用空腹一次性注射STZ溶液(40 mg/kg),注射STZ 3天后,大鼠空腹血糖高于16.7 mmol,尿糖(+++),视为糖尿病大鼠模型建立成功.建模后,分正常组,模型组,二甲双胍组,二甲双胍和辛伐他汀联用组,检测胫骨骨密度.结果 糖尿病大鼠胫骨骨密度低于二甲双胍组低于二甲双胍和辛伐他汀联用组低于正常组(P＜0.01).结论 糖尿病状态下胫骨骨密度低于正常,经过治疗后骨密度改善明显,联用组优于单独使用二甲双胍组.     

岳阳地区50岁以上人群25经维生素D水平及其与骨密度的关系

目的 通过测定269名岳阳地区50岁以上人群血清25经维生素D(25(OH)D)和骨密度(BMD)水平,分析岳阳地区50岁以上人群的维生素D ( VitD)状况,并探讨其与BMD的关系。方法 采集受试者的血清后,用电化学发光法测定血清25(OH)D水平,并同时应用双能X线吸收仪测定腰椎及髓部BMD。结果 所有受试者中,VitD严重缺乏者占24. 2 %,缺乏者占45. 0%,不足者占24. 5 %,充足者占6. 3。男、女性受试者的25(OH)D水平、腰椎及髓部的BMD间有统计学差异(P<0.001),男性高于女性。男性各年龄段间25(OH)D水平及各部位BMD无统计学差异(P=0. 101 ,P = 0. 261 ,0. 055 ,0. 170 ,0. 108 ,0. 051 ) ;女性各年龄段之间25(OH)D水平及腰椎BMD无统计学差异(P = 0. 364 , 0. 063 ) ;髓部BMD有统计学差异(P < 0. 001 ),随着年龄的增长而逐步减低。男性受试者中,不同25(OH)D水平组间股骨颈、转子间区及整髓BMD无统计学差异(P = 0. 076 , 0. 425 , 0. 122 );腰椎、大转子区BMD水平间有统计学差异(P=0. 027 , 0. 017 ) , VitD充足组腰椎BMD高于其他各组(P = 0. 005 , 0. 025 , 0. 009 );不足组、严重缺乏组大转子区BMD高于缺乏组(P = 0. 021, 0. 005 )。女性受试者中,不同25(OH)D水平组各部位BMD均无统计学差异(P = 0. 616 , 0. 739 , 0. 559 ; 0. 608 , 0. 641)。结论 在湖南岳阳地区50岁以上人群存在严重的维生素D缺乏及不足;对于维生素D状况与骨密度之间可能无直接关联,需加大样本量进一步观察。