Metabolic dysfunction-associated fatty liver disease and osteoporosis: the mechanisms and roles of adiposity

Nonalcoholic fatty liver disease (NAFLD) has recently been renamed metabolic dysfunction-associated fatty liver disease (MAFLD) by international consensus. Both MAFLD and osteoporosis are highly prevalent metabolic diseases. Recent evidence indicates that NAFLD increases the risk of low bone mineral density and osteoporosis, likely mediated by obesity. NAFLD has a close association with obesity and other metabolic disorders. Although obesity was previously thought to protect against bone loss, it now heightens osteoporotic fracture risk. This overview summarizes current clinical correlations between obesity, NAFLD, and osteoporosis, with a focus on recent insights into potential mechanisms interconnecting these three conditions. This study reviewed the scientific literature on the relationship between obesity, nonalcoholic fatty liver disease, and osteoporosis as well as the scientific literature that reveals the underlying pathophysiologic mechanisms between the three. Emerging evidence suggests obesity plays a key role in mediating the relationship between NAFLD and osteoporosis. Accumulating laboratory evidence supports plausible pathophysiological links between obesity, NAFLD, and osteoporosis, including inflammatory pathways, insulin resistance, gut microbiota dysbiosis, bone marrow adiposity, and alterations in insulin-like growth factor-1 signaling. Adiposity has important associations with NAFLD and osteoporosis, the underlying pathophysiologic mechanisms between the three may provide new therapeutic targets for this complex patient population.