Effects of Sleeve Gastrectomy on Calcium Metabolism and the Skeleton
Condition: Calcium Metabolism Disorders; Morbid Obesity
MeSH terms: Obesity, Morbid; Metabolic Diseases; Calcium Metabolism Disorders
Study type: Observational

Summary: 
      In this pre-post observational study, the investigators will enroll and follow a cohort of
      about 50 adults undergoing sleeve gastrectomy surgery for weight loss. Pre-operatively and at
      6 and 12 months post-operatively, the investigators will use state-of-the-art metabolic and
      imaging techniques to evaluate calcium metabolism and skeletal health. Specific outcomes
      include intestinal calcium absorption capacity, bone mineral density (BMD) assessed by
      dual-energy X-ray absorptiometry (DXA) and quantitative computed tomography (QCT), and bone
      structure assessed by QCT and high-resolution peripheral QCT (HR-pQCT).
    

Detailed description: 
      Obesity is a chronic disease of staggering proportions. Because weight loss through diet and
      exercise is difficult to attain and maintain, there is escalating interest in surgical weight
      loss procedures, including Roux-en-Y gastric bypass. Gastric bypass results in marked and
      durable weight loss and improvement in comorbidities in the general population and in our
      veteran patients. However, growing evidence indicates that gastric bypass can have negative
      effects on the skeleton, increasing bone turnover and decreasing bone mineral density (BMD).
      This is of critical concern given the tremendous impact of osteoporosis and fracture in both
      men and women. Vitamin D deficiency due to obesity and post-surgical malabsorption may
      partially explain the decline in bone mass observed after gastric bypass. Other factors are
      likely involved as well, such as non-vitamin D-mediated calcium malabsorption, signals
      related to decreased skeletal loading, and changes in fat-secreted hormones or estrogen (due
      to changes in fat mass and body composition).

      We will characterize the effects of gastric bypass on calcium metabolism and the skeleton in
      a cohort of 80 men and women whose serum 25-hydroxyvitamin D levels are supplemented and
      maintained at ≥30 ng/mL. First, we will test the hypothesis that intestinal calcium
      absorption is impaired following gastric bypass, even in the setting of vitamin D
      sufficiency. We will do this by measuring fractional calcium absorption pre-operatively and 6
      months post-operatively using dual stable isotopic tracers (Aim 1). Then, we will test the
      hypothesis that gastric bypass results in decreased BMD and in structural changes associated
      with impaired skeletal strength. We will do this by performing dual-energy X-ray
      absorptiometry (DXA), quantitative computed tomography (QCT), and high-resolution peripheral
      QCT (HR-pQCT) pre-operatively and 6 and 12 months post-operatively (Aim 2). QCT and HR-pQCT
      are advanced imaging techniques that have distinct advantages over standard methods but have
      not yet been applied to this population. Finally, we will assess body composition changes by
      anthropometry, DXA, and QCT, and changes in fat-secreted hormones, and we will evaluate the
      relationship between changes in skeletal parameters and changes in body composition and
      hormones (Aim 3). This research is expected to impact the clinical care of gastric bypass
      patients by helping to shape recommendations about post-operative nutrition, BMD screening,
      and potential therapy.

      As an ancillary study aim (Aim 4), we will assess vertebral bone marrow fat pre- and
      post-operatively in a subgroup of participants, and we will evaluate the relationships
      between change in vertebral bone marrow fat, changes in body composition and fat-secreted
      hormones, and changes in skeletal parameters. The participants in this subgroup will have the
      option of undergoing additional knee tissue composition evaluation, allowing us to evaluate
      the relationship between weight loss and change in knee health. In order to develop and
      refine the magnetic resonance (MR) sequences we will use for Aim 4, we will scan a small
      group of healthy controls at baseline and after 6 months.
    

Observational model: Cohort
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        Obese men and women undergoing sleeve gastrectomy surgery
      
Biospecimen description: 
      serum, urine
    
Keywords: sleeve gastrectomy, bariatric surgery