Relationship of Aging, Inflammation, and Skeletal Stem Cells and Their Effects on Fracture Repair.

Proper regulation of the inflammatory phase of fracture healing is essential. Aging is associated with chronic inflammation, which inhibits bone formation and promotes bone resorption. Osteogenic differentiation and anti-senescence pathways in skeletal stem cells are impaired in geriatric fractures. As the population ages, fragility fractures will continue to represent a significant clinical problem, which will require innovative clinical solutions. Skeletal stem cells in geriatric individuals demonstrate defects in anti-senescence pathways that lead to impaired osteogenic differentiation in vitro in humans. Small molecule-based therapies can partially reverse the aging phenotype. In the future, molecular- or cell-based therapies modulating either inflammatory cells or skeletal stem cells represent potential therapeutic targets to augment contemporary fracture healing interventions in osteoporotic or aging individuals.