A new active vitamin D3 analog, eldecalcitol, prevents the risk of osteoporotic fractures--a randomized, active comparator, double-blind study

Background

Eldecalcitol is an analog of 1,25-dihydroxyvitamin D₃ that improves bone mineral density; however, the effect of eldecalcitol on the risk of fractures is unclear. The objective of this study is to examine whether eldecalcitol is superior to alfacalcidol in preventing osteoporotic fractures. This trial is registered with ClinicalTrials.gov, number NCT00144456.

Methods and results

This 3 year randomized, double-blind, active comparator, superiority trial tested the efficacy of daily oral 0.75 μg eldecalcitol versus 1.0 μg alfacalcidol for prevention of osteoporotic fractures. 1054 osteoporotic patients 46 to 92 years old were randomly assigned 1:1 to receive eldecalcitol (n = 528) or alfacalcidol (n = 526). Patients were stratified by study site and serum 25-hydroxyvitamin D level. Patients with low serum 25-hydroxyvitamin D levels (< 50 nmol/L) were supplemented with 400 IU/day vitamin D₃. Primary end point was incident vertebral fractures. Secondary end points included any non-vertebral fractures and change in bone mineral density and bone turnover markers. Compared with the alfacalcidol group, the incidence of vertebral fractures was lower in eldecalcitol group after 36 months of treatment (13.4 vs. 17.5%; hazard ratio, 0.74; predefined 90% confidence interval [CI], 0.56–0.97). Eldecalcitol reduced turnover markers and increased bone mineral density more strongly than alfacalcidol. Eldecalcitol reduced the incidence of three major non-vertebral fractures, which was due to a marked reduction in wrist fractures by a post-hoc analysis (1.1 vs. 3.6%; hazard ratio, 0.29; 95% CI, 0.11–0.77). Among the adverse events, the incidence of increase in serum and urinary calcium was higher in the eldecalcitol group, without any difference in glomerular filtration rate between the two groups.

Conclusions

Eldecalcitol is more efficacious than alfacalcidol in preventing vertebral and wrist fractures in osteoporotic patients with vitamin D sufficiency, with a safety profile similar to alfacalcidol.     

骨质疏松性椎体压缩骨折PKP与保守治疗的随机对照研究

目的 比较经皮椎体后凸成形术(percutaneous kyphoplasty,PKP)与保守疗法对骨质疏松性椎体压缩骨折患者的有效性和安全性的研究.方法 本研究对象为2007年7月至2010年7月间的164 例患者.骨质疏松性脊柱骨折发生2周以内的急性患者和发生在2～8周内的亚急性患者被随机分为保守治疗组和PKP治疗...     

Blunt traumatic vertebral artery injury: a clinical review

Blunt traumatic vertebral injury (TVAI) is frequently associated with head and neck injury and is being detected with increasing frequency due to improved imaging of the trauma patient. In a few cases, it can lead to potentially fatal posterior circulation ischaemia There is debate in the literature regarding whether TVAI should be actively screened for and, if so, how. Management of TVAI may be conservative, medical (antiplatelet agents or anticoagulation), endovascular or open surgery. We review the literature concerning the mechanisms and presentation of TVAI following blunt injury and the current screening recommendations. Management strategies proposed are based on the radiological grade and clinical severity of TVAI, where high-grade symptomatic injuries and high-grade injuries in patients where anticoagulation is contraindicated are treated endovascularly and asymptomatic or low-grade injuries are managed with anticoagulation where it is not contraindicated. Follow-up is via CT angiography to assess for resolution of the injury.     

Regional variations of vertebral trabecular bone microstructure with age and gender

The vertebral trabecular bone has a complex three-dimensional (3D) microstructure, with inhomogeneous morphology. A thorough understanding of regional variations in the microstructural properties is crucial for evaluating age- and gender-related bone loss of the vertebra, and may help us to gain more insight into the mechanism of the occurrence of vertebral osteoporosis and the related fracture risks. INTRODUCTION: The aim of this study was to identify regional differences in 3D microstructure of vertebral trabecular bone with age and gender, using micro-computed tomography (micro-CT) and scanning electron microscopy (SEM). METHODS: We used 56 fourth lumbar vertebral bodies from 28 women and men (57-98 years of age) cadaver donors. The subjects were chosen to give an even age and gender distribution. Both women and men were divided into three age groups, 62-, 77- and 92-year-old groups. Five cubic specimens were prepared from anterosuperior, anteroinferior, central, posterosuperior and posteroinferior regions at sagittal section. Bone specimens were examined by using micro-CT and SEM. RESULTS: Reduced bone volume (BV/TV), trabecular number (Tb.N) and connectivity density (Conn.D), and increased structure model index (SMI) were found between ages 62 and 77 years, and between ages 77 and 92 years. As compared with women, men had higher Tb.N in the 77-year-old group and higher Conn.D in the 62- and 77-year-old groups. The central and anterosuperior regions had lower BV/TV and Conn.D than their corresponding posteroinferior region. Increased resorbing surfaces, perforated or disconnected trabeculae and microcallus formations were found with age. CONCLUSION: Vertebral trabeculae are microstructurally heterogeneous. Decreases in BV/TV and Conn.D with age are similar in women and men. Significant differences between women and men are observed at some microstructural parameters. Age-related vertebral trabecular bone loss may be caused by increased activity of resorption. These findings illustrate potential mechanisms underlying vertebral fractures.     

先天性脊柱侧凸患者脊椎畸形及椎管内畸形的特点

目的:探讨先天性脊柱侧凸(CS)患者脊椎畸形与椎管内畸形的特点及两者间的关系.方法:对我院2005年9月～2007年5月收治的123例CS患者的影像学资料进行回顾性分析.统计不同类型脊椎畸形及不同类型椎管内畸形的特点,分析两者之间的关系.结果:123例患者的脊椎畸形中,28例(22.8%)为形成障碍(FF).43例(35.0%)为分节障碍(SF),52例(42.2%)为混合型障碍(MT).28例FF均在胸腰椎,其中前方结构畸形(AM)19例(67.9%),前后方结构畸形(APM)9例(32.1%);单节段畸形(SM)19例(67.9%),多节段畸形(MM)9例(32.1%).43例SF中,AM 9例(20.9%),后方结构畸形(PM)3例(7.0%),APM 31例(72.1%);SM 9例(20.9%),MM 34例(79.1%);214个节段受累,胸椎196个.52例MT中,AM 6例(11.5%),APM 46例(78.5%);SM 6例(11.5%),MM 46例(78.5%).37例(31.7%)患者有椎管内畸形,其中脊髓纵裂14例,低位脊髓2例,脊髓纵裂合并低位脊髓21例.35例脊髓纵裂患者中34例位于胸椎、腰椎或跨越胸腰椎,33例为SF或MT:23例低位脊髓中21例发生于SF或MT.结论:FF好发于胸椎和腰椎,多为单纯AM,SF和MT好发于胸椎,多为APM.脊椎畸形好发于胸椎,脊髓纵裂好发于胸椎和腰椎,脊髓纵裂和低位脊髓好发于SF或MT.     

CT介导同轴套管针脊柱病变经皮活检术

目的探讨CT介导同轴套管针经皮活检术在脊柱病变临床诊治中的价值。方法CT引导下同轴穿刺套管针经皮穿刺活检脊柱病变37例,其中胸椎9例,腰椎13例,骶椎8例,胸腰椎同时累及7例。根据病变的部位,采用经椎弓根或椎旁入路,进入病变部位后旋转套管切割病变组织,送组织学检查。结果所有37例患者均穿刺成功,每例患者获穿刺组织块1～4块,平均2.1块;34例获明确诊断,分别为转移性肿瘤15例,结核9例,脊索瘤5例,多发性骨髓瘤2例,骨巨细胞瘤2例,嗜酸性细胞肉芽肿1例,成功率91.9%;无一例严重并发症。结论CT介导同轴套管针脊柱病变经皮活检术诊断率高,并发症少,且微创、安全,价格低廉,值得在临床推广应用。     

微创复位椎体后凸成形治疗重度骨质疏松性脊柱骨折

目的探讨微创复位椎体后凸成形(MIRKP)治疗重度骨质疏松性脊柱骨折的临床疗效。方法11例12个椎体骨质疏松、楔形压缩或爆裂性骨折,经CT、MRI检查后判断椎体后缘骨块突入椎管内的程度及脊髓有无受压后,单侧微创复位恢复椎体高度,另一侧行经皮穿刺,并C型臂X线机定位后注入骨水泥。结果8例Frankel神经分类D级均恢复至E级;Cobb角平均恢复15°;椎管骨块侵占率平均减少21%;平均灌注骨水泥5.2ml。随访平均7.6个月,未发现手术并发症及椎体高度的丢失。结论MIRKP治疗骨质疏松性脊柱骨折安全、有效,对严重骨质疏松性脊柱骨折有很好的疗效。     

Flattening of sagittal spinal curvature as a predictor of vertebral fracture

Summary In a 12-year prospective study of 100 adult volunteers, incident vertebral fractures were analyzed for potential predictors. Decreased sagittal spinal curvature and pre-existing fractures were identified as independent predictors. The risk of vertebral fracture increased to 8.6-fold with a 1 SD decrease in both thoracic and lumbar curves. Introduction Physiological spinal curvature acts as a shock absorber: however, it has not been demonstrated whether reduced spinal curvature is a risk of vertebral fracture. The aim of this prospective study is to assess the relationship between the extent of sagittal spinal curvature and incidence of vertebral fractures. Methods One hundred community-based volunteers aged 50+ years were followed radiologically for at least 10 years. Entire spine radiograms of volunteers in erect position were used for evaluating sagittal spinal curvatures, grade of osteoporosis, and incident vertebral fractures. Results Mean baseline age was 61.9 years and mean follow-up period was 12.0 years. In multivariate analysis, preexisting vertebral fracture (relative risk [RR] 3.70, 95% confidence interval [CI] 1.22-11.20), and a decrease in either thoracic or lumbar curvature by 1-SD (RR 3.06, 95% CI 1.04-9.00) were independent predictors. The fracture risk even increased in the presence of a 1-SD decrease in both thoracic and lumbar curvature (RR 8.64, 95% CI 1.39-53.78). Conclusions Reduction of physiological curvatures in both thoracic and lumbar spine led to the increased risk of vertebral fracture by more than eightfold. The importance of evaluating sagittal spinal alignment should be emphasized, because it might indicate the risk of the first vertebral fracture, which is another strong predictor of subsequent fractures.     

Association between height loss and bone loss, cumulative incidence of vertebral fractures and future quality of life: the Miyama study

Introduction The study aimed to clarify associations between height loss, bone loss and the quality of life (QOL) score among general inhabitants of Miyama, a rural Japanese community. This population-based epidemiological study was conducted in Miyama, a village located in a mountain area in Wakayama Prefecture, Japan. Methods A list of all inhabitants comprising 1,543 inhabitants (716 men, 827 women) born in this village between 1910–1949 was compiled. From the above whole cohort, a subcohort to measure bone mineral density (BMD) was recruited, consisting of 400 participants, divided into four groups of 50 men and 50 women each, and stratified into age decades by decade of birth-year (1910–1919, 1920–1929, 1930–1939 or 1940–1949). BMD measurement, physical measurements of height (cm) and body weight (kg) were taken, and body mass index (BMI; kg/m²) were calculated. BMD and anthropometric measurements were repeated on the same participants at 3, 7 and 10 years after baseline measurement (1993, 1997 and 2000). Results and discussion Among 299 of 400 participants, changes in height over 10 years for men in their 40s, 50s, 60s and 70s were −0.7 cm, −0.5 cm, −1.2 cm and −1.5 cm, respectively, compared with −0.7 cm, −1.4 cm, −2.1 cm and −3.7 cm in women, respectively. No significant relationships between change in height and rate of change in BMD at the lumbar spine and femoral neck after adjustment for age in men (lumbar spine, β = 0.058, standard error of the mean (SE) = 0.031, P = 0.501, R² = 0.038; femoral neck, β = 0.100, SE = 0.038, P = 0.228, R² = 0.121) were identified. By contrast, among women, a significant positive association was identified between height change and change rate of BMD at the lumbar spine after adjusting for age (β = 0.221, SE = 0.039, P = 0.012, R² = 0.069), while no significant relationship was found between height change and change rate at the femoral neck (β = 0.107, SE = 0.039, P = 0.229, R² = 0.048). No significant relationship was noted between vertebral fractures (VFx) and height at baseline in men and women (men: odds ratio (OR) 0.93, 95% confidence interval (CI) 0.81–1.05, P = 0.24; women: OR 0.97, 95% CI 0.87–1.08, P = 0.58) or between VFx and height loss (men: OR 1.31, 95% CI 1.00–1.71, P = 0.051; women: OR 1.20, 95% CI 0.94–1.53, P = 0.14). In both men and women, no significant relationship was identified between utility of the EuroQol EQ5D questionnaire and height at baseline (men: β = −0.148, SE = 0.003, P = 0.202, R² = 0.076; women: β = 0.127, SE = 0.004, P = 0.235, R² = 0.048), and height change (men: β = −0.078, SE = 0.008, P = 0.452, R² = 0.065; women: β = 0.053, SE = 0.010, P = 0.608, R² = 0.038).     

椎体位移与椎间盘内压力变化的实验研究

目的 探讨椎体位移对椎间盘内压力的影响,纠正椎体位移在手法治疗椎间盘突出症中的意义。方法 选择8只杂种犬,取L3－L5段脊柱椎体,固定在自制的器械上,将L4椎体后仰前倾,测量新鲜杂种狗腰椎椎体位移及纠正后椎间盘内压力变化。结果 当椎体后仰椎间盘后外侧压力增加明显（P＜0.01）,椎体前倾时椎间盘后外侧压力减小明显（P＜0.01）,而当椎体恢复原位,压力恢复原水平,两者无显著差异（P＞0.05）。结论 1.椎体位移使相邻椎间盘局部应力发生变化。椎体后仰时下方椎间盘后外侧力明显增大。2.手法治疗通过纠正椎体位移,可以确切、有效的使来自椎间盘内部的异常压力消失,解除对神经根的压迫从而达到治愈的目的。