6 Years Study on Changes in Bone Quality, Bone Turnover and Curve Severity in AIS With and Without Calcium and Vit-D Supplementation
Condition: Scoliosis; Vitamin D; Bone
MeSH terms: Scoliosis
Study type: Observational

Summary: 
      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:

             1. Group A: subjects followed at a mean of 4 years after completion of 2-year calcium
                and Vit-D supplementation and

             2. Group B: subjects without calcium and Vit-D supplementation

        2. 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
    

Detailed description: 
      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.

      This six years longitudinal follow-up study with 2-year active supplementation period and
      4-year post-withdrawal follow up for this cohort of adolescent girls is unique. Not only are
      the effects of calcium and vitamin D supplementation being followed, the placebo group in the
      original clinical trial provides the longitudinal changes on anthropometric, bone density,
      bone quality parameters and curve severity which will yield important reference information
      for local adolescents with AIS.
    

Observational model: Cohort
Time perspective: Other
Sampling method: Non-Probability Sample
Study population: 
        All 330 subjects from the Cal study will be invited to participate. Order of recruitment
        will follow the order of recruitment during the initial study at a first-entry first-serve
        basis.
      
Biospecimen description: 
      Serum
    
Keywords: scoliosis; spinal deformity; vitamin D; bone health