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临床试验/NCT02904421
NCT02904421已完成不适用

A Six Years Longitudinal Cohort Study on the Changes in Bone Density, Bone Quality and Its Association With Bone Turnover Markers and Curve Severity in Adolescent Idiopathic Scoliosis With and Without 2 Years of Calcium and Vit-D Supplementation

Chinese University of Hong Kong1 个研究点 分布在 1 个国家目标入组 330 人开始时间: 2016年10月最近更新:
适应症

试验速览

阶段
不适用
状态
已完成
入组人数
330
试验地点
1
主要终点
Change from baseline clinical features of scoliosis at end of 2 year supplementation and at 4 years post-treatment follow up

研究概览

简要总结

The study aimed to:

  1. To investigate and compare the changes in bone mineral density (BMD), trabecular bone micro-architecture, bone strength, and curve severity at a mean of 6 years longitudinal follow up in AIS girls with low bone mass between Group A and B:

  2. Group A: subjects followed at a mean of 4 years after completion of 2-year calcium and Vit-D supplementation and

  3. Group B: subjects without calcium and Vit-D supplementation

  4. To evaluate the correlation between changes in BMD, trabecular bone micro-architecture, and bone strength documented in Objective 1 with changes in serum bone turnover markers

详细描述

Adolescent Idiopathic Scoliosis (AIS) is a complex three-dimensional spinal deformity mostly affecting girls in the peri-pubertal period. Prevalence ranges from 2 to 4% in the general population. When the deformity becomes severe, serious morbidities can occur including early back degeneration, cardiopulmonary compromise, grossly deformed torso and associated psychosocial issues which could pose serious health threats for these young patients.

One important health threat that deserves special attention is osteopenia as defined by Bowden et al. for children having BMD age and gender-adjusted Z-score < -1. 30-38% of AIS girls were osteopenic. Osteopenia could persist across puberty and was found to be a significant and independent prognostic factor for curve progression in AIS. Osteopenia was also found to be associated with low dietary calcium (Ca) intake at a median of 400mg/day among AIS girls. The low Ca intake was significantly correlated with age-adjusted peripheral volumetric bone mineral density (vBMD) measured by peripheral quantitative computed tomography (pQCT), as well as axial and peripheral areal BMD (aBMD) measured by Dual-Energy X-ray Absorptiometry (DXA).

Low calcium intake when coupled with low Vit-D status can seriously affect a child's bone health. Without Vit-D, only 10 to 15% of dietary calcium is absorbed, and 1,25-(OH)2Vit-D can increase intestinal calcium absorption to 30-40%. Vit-D insufficiency or disturbance in Vit-D physiology is associated with osteopenia, deranged muscle function and ligamentous laxity which could potentially predispose AIS subjects to curve progression.

Given that serum 25(OH)Vit-D level was also found to be low at a mean level of 41.6 nmol/L among AIS subjects, our group has conducted the first 2-year randomized double-blinded placebo-controlled trial using calcium and Vit-D supplementation for young AIS girls with low bone mass (the Cal study). There were three study groups in the trial, namely Group 1 (the placebo group), Group 2 (the low-dose treatment group with 600mg calcium + 400IU Vit-D3/day) and Group 3 (the high-dose treatment group with 600mg calcium + 800IU Vit-D3/day). The study showed strong evidences of positive bone accretion effects and therapeutic control of curve progression in groups with supplementation (Group 2 and 3). Following the therapeutic gain in BMD and improvement in bone quality with 2-year intervention with calcium and Vit-D supplementation, it will be important to evaluate if the effects persist after supplement withdrawal. This study would help to address this key issue by evaluating whether the beneficial effects of 2-year calcium and Vit-D supplementation persist at an average of 4 years after withdrawal of supplementation. The BMD, trabecular bone micro-architecture, bone strength, image-based and serum bone turnover parameters, and curve severity at 4 years after withdrawal of supplement would be compared with measurements done before and at end of supplementation.

Outcome of this study will provide important scientific data on the long term effects of 2-year calcium and Vit-D supplementation, thus justifying the need of lifestyle modification, duration and dose of supplementation for better bone health and curve control in adolescents suffering from AIS. If the beneficial effects are proven to be sustainable, the 2-year calcium and Vit-D supplements can be incorporated into the treatment protocol for AIS not only in Hong Kong, but also in Mainland China and other parts of the world; otherwise longer period of supplementation for sustained positive bone accretion effects and prevention of curve progression will be desirable for attaining peak bone mass and curve control to prevent osteopenia-related and scoliosis-related complications when approaching adulthood.

研究设计

研究类型
Observational
观察模型
Cohort
时间视角
Other

入排标准

年龄范围
16 Years 至 21 Years(Child, Adult)
性别
Female
接受健康志愿者

入选标准

  • Subjects from the Cal study

排除标准

  • Subjects that are pregnant
  • Subjects with fracture

结局指标

主要结局

Change from baseline clinical features of scoliosis at end of 2 year supplementation and at 4 years post-treatment follow up

时间窗: baseline, end of 2 year supplementation, 4 years post-treatment follow up

A long standard standing postero-anterior (PA) whole spine radiograph will be used for grading curve severity in terms of Cobb angle according to the standard Cobb method.

Change from baseline BMD Measurement at end of 2 year supplementation and at 4 years post-treatment follow up

时间窗: baseline, end of 2 year supplementation, 4 years post-treatment follow up

Areal BMD (g/cm2) and BMC (g/cm) of bilateral hips (femoral neck) will be measured by DXA.

Change from baseline volumetric BMD (vBMD), bone geometry and trabecular bone micro-architecture at end of 2 year supplementation and at 4 years post-treatment follow up

时间窗: baseline, end of 2 year supplementation, 4 years post-treatment follow up

Detailed bone measurement of the non-dominant distal radius will be carried out with the in-vivo HR-pQCT using an established measurement protocol.

Change from baseline bone mechanical strength at end of 2 year supplementation and at 4 years post-treatment follow up

时间窗: baseline, end of 2 year supplementation, 4 years post-treatment follow up

Finite element analysis (FEA) will be used to assess the bone strength non-invasively. Finite element (FE) models of the radius will be created directly from the HR-pQCT images using Scanco FE solver integrated in the IPL software.

Change from baseline biochemical markers for bone formation and resorption at end of 2 year supplementation and at 4 years post-treatment follow up

时间窗: baseline, end of 2 year supplementation, 4 years post-treatment follow up

Serum P1NP and β-CTx will be assayed to determine bone formation and resorption activity.

Change from baseline serum Vitamin D concentration at end of 2 year supplementation and at 4 years post-treatment follow up

时间窗: baseline, end of 2 year supplementation, 4 years post-treatment follow up

Serum 25(OH)Vit-D concentrations will be measured by liquid chromatography isotope-dilution electrospray ionization tandem mass spectrometry (LCTMS).

次要结局

  • Change from baseline anthropometric measurements and maturity assessment at end of 2 year supplementation and at 4 years post-treatment follow up(baseline, end of 2 year supplementation, 4 years post-treatment follow up)
  • Change from baseline dietary intakes and physical activity at end of 2 year supplementation and at 4 years post-treatment follow up(baseline, end of 2 year supplementation, 4 years post-treatment follow up)

研究者

申办方类型
Other
责任方
Principal Investigator
主要研究者

Tsz-ping Lam

Clinical Assistant Professor

Chinese University of Hong Kong

研究点 (1)

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