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 bariatric surgery. However, those who undergo bariatric surgery may be at risk for long-term complications. Roux-en-Y gastric bypass, the most common bariatric procedure in the US in recent years, is known to have negative effects on bone health, including impaired calcium absorption, increased bone turnover, decreased bone mineral density (BMD), and increased fracture risk. Sleeve gastrectomy is a newer bariatric procedure in which most of the stomach is removed but the intestinal tract remains unaltered. Its use has risen dramatically, due to evidence that its lower invasiveness results in fewer complications, and it is poised to overtake gastric bypass. However, the effects of sleeve gastrectomy on calcium metabolism and the skeleton remain poorly understood, and as a result, guidelines about prevention of and screening for post-operative metabolic bone disease are extremely limited. Our objective in this application is to define the effects of sleeve gastrectomy on intestinal calcium absorption, BMD, and bone structure-in absolute terms and relative to gastric bypass. Our central hypothesis is that sleeve gastrectomy adversely affects bone metabolism, although to a lesser extent than gastric bypass. To test this hypothesis, we will apply metabolic and imaging techniques we have already used successfully to understand the skeletal effects of gastric bypass. We will enroll and follow a pre-post cohort of 50 adults undergoing sleeve gastrectomy. Serum 25-hydroxyvitamin D levels will be repleted and maintained at ?30 ng/mL, to remove the effect of the vitamin D deficiency so common in obesity and with dietary restriction. First, we will test the hypothesis that intestinal calcium absorptionis impaired following sleeve gastrectomy, even in the setting of robust vitamin D status. We will do this by measuring fractional calcium absorption pre- operatively and 6 months post-operatively using dual stable isotopic tracers (Aim 1). Next, we will test the hypothesis that sleeve gastrectomy leads to decreased BMD and to microstructural 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 the sleeve gastrectomy population. Finally, we will compare changes after sleeve gastrectomy with changes after gastric bypass, using data from our recently completed gastric bypass study, which employed an identical approach and measurements (Aim 3). We hypothesize that negative calcium and skeletal effects of sleeve gastrectomy are less severe than those of gastric bypass. This research has the potential to shape the care of bariatric patients by informing procedure-specific approaches to prevent potential skeletal complications of otherwise beneficial operations.

Public Health Relevance

Bariatric surgery produces durable weight loss, improves comorbidities, and decreases mortality, but those who undergo surgical weight loss may be at risk for long-term complications. Roux-en-Y gastric bypass is known to have negative effects on bone health, but the skeletal effects of the increasingly popular sleeve gastrectomy procedure remain poorly understood. A better understanding of the effects of sleeve gastrectomy on calcium metabolism and the skeleton is expected to positively impact the clinical care of bariatric patients, directly shaping procedure-specific, evidence-based recommendations about calcium supplementation and bone density monitoring, and contributing to the fully informed decision-making of patients and providers.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Research Project (R01)
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Neurological, Aging and Musculoskeletal Epidemiology (NAME)
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Teff, Karen L
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Northern California Institute Research & Education
San Francisco
United States
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Schafer, Anne L; Kazakia, Galateia J; Vittinghoff, Eric et al. (2018) Effects of Gastric Bypass Surgery on Bone Mass and Microarchitecture Occur Early and Particularly Impact Postmenopausal Women. J Bone Miner Res 33:975-986
Kim, Tiffany Y; Schwartz, Ann V; Li, Xiaojuan et al. (2017) Bone Marrow Fat Changes After Gastric Bypass Surgery Are Associated With Loss of Bone Mass. J Bone Miner Res 32:2239-2247
Schafer, Anne L (2017) Vitamin D and intestinal calcium transport after bariatric surgery. J Steroid Biochem Mol Biol 173:202-210
Kim, Tiffany Y; Schafer, Anne L (2016) Diabetes and Bone Marrow Adiposity. Curr Osteoporos Rep 14:337-344