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Abstract
Musculoskeletal disorders are a leading cause of years lived with a disability world-wide and represent a major healthcare expenditure in the United States. Nearly 10 million people living in the United States have osteoporosis, a condition associated with an increased risk of fractures. The National Osteoporosis Foundation highlights a myriad of factors that contribute to bone health across the lifespan, including nutrition, physical activity, medications, and hormones. Nutrition plays a pivotal role in maintaining lifelong bone health, and cross-talk between the gut and bone–often referred to as the “gut-bone axis”¬–is hypothesized to mediate the nutritional effects on bone. Incretin hormones, such as glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1), acutely regulate postprandial bone metabolism. However, the biological mechanisms through which nutrition impacts bone health via the gut-bone axis have not been clearly defined. The objective of this dissertation is to examine the relationship between nutrition, incretin hormones, and bone metabolism in healthy adults and in individuals with endocrine-related conditions such as diabetes and cystic fibrosis-related diabetes (CFRD). In manuscript #1, a cross-sectional study involving 10 healthy emerging adults (ages 18-25) was conducted to determine the effects of glucose ingestion on C-terminal telopeptide (CTX), a biomarker of bone resorption. Glucose ingestion resulted in an anti-resorptive effect on bone metabolism by minute 30. Manuscript #2 is a systematic review and meta-analysis that summarizes the overall effect of GIP administration on CTX based on previously conducted randomized controlled crossover trials. GIP exerts an anti-resorptive effect on bone, which may be modified in individuals with diabetes. In manuscript #3, a secondary analysis was performed to evaluate the effects of intravenous incretin hormone infusion on bone resorption in adults with cystic fibrosis (CF). CTX decreased during GIP infusion, but not during placebo, indicating that GIP induces a bone anti-resorptive effect in individuals with pancreatic-insufficient CF (PI-CF). Overall, findings suggest that both glucose ingestion and incretin hormone infusion have acute anti-resorptive effects on bone. However, metabolic conditions that disrupt the gut-bone axis, such as type 1 and type 2 diabetes and PI-CF, may increase the risk of bone disease in individuals with entero-endocrinopathies.