Understanding the mechanisms that underlie changes in the gut-bone axis with bariatric surgery-induced bone loss and identify the important components to consider strategies that reduce skeletal complications.
Model of how gastric secretory factors contribute to VSG-caused bone loss.
Bariatric surgery-associated skeletal complications have been observed since the early 1990s, and lead to up to two-fold increase in fracture risk. The most common bariatric surgery is vertical sleeve gastrectomy (VSG), which leads to ~3-7% bone loss at the axial skeleton after 6-24 months. Current clinical management includes bone mineral density assessments, consumption of adequate dietary calcium, vitamin D, and protein, and performance of weight-bearing exercise. These countermeasures minimize, but do not fully prevent bone loss secondary to bariatric surgery. A better mechanistic understanding of bone loss associated with bariatric surgery is necessary to properly design and evaluate preventive and therapeutic strategies.
Changes in gut hormones and microbiota are alternative mechanisms driving bone loss, but the effects of the major surgical site (the stomach) have been largely neglected. We propose that gastric hormones contribute to bariatric surgery-induced skeletal complications. My lab found gastric X/A-like cells (P/D1 cell in humans), a unique endocrine cell population, contribute to the regulation of global lipid metabolism, marrow adiposity and bone formation, suggesting a stomach-bone axis. Our goals are: 1) to determine the effects of gastric X/A-like cell-derived secretory factors on VSG-induced bone loss; and 2) to identify and characterize gastric hormones from X/A-like cells that regulate skeletal homeostasis.