Published online Jun 26, 2019. doi: 10.4252/wjsc.v11.i6.281
Peer-review started: March 22, 2019
First decision: April 11, 2019
Revised: April 26, 2019
Accepted: June 12, 2019
Article in press: June 12, 2019
Published online: June 26, 2019
Successful fracture healing requires the simultaneous regeneration of both the bone and vasculature; mesenchymal stem cells (MSCs) are directed to replace the bone tissue, while endothelial progenitor cells (EPCs) form the new vasculature that supplies blood to the fracture site. In the elderly, the healing process is slowed, partly due to decreased regenerative function of these stem and progenitor cells. MSCs from older individuals are impaired with regard to cell number, proliferative capacity, ability to migrate, and osteochondrogenic differentiation potential. The proliferation, migration and function of EPCs are also compromised with advanced age. Although the reasons for cellular dysfunction with age are complex and multidimensional, reduced expression of growth factors, accumulation of oxidative damage from reactive oxygen species, and altered signaling of the Sirtuin-1 pathway are contributing factors to aging at the cellular level of both MSCs and EPCs. Because of these geriatric-specific issues, effective treatment for fracture repair may require new therapeutic techniques to restore cellular function. Some suggested directions for potential treatments include cellular therapies, pharmacological agents, treatments targeting age-related molecular mechanisms, and physical therapeutics. Advanced age is the primary risk factor for a fracture, due to the low bone mass and inferior bone quality associated with aging; a better understanding of the dysfunctional behavior of the aging cell will provide a foundation for new treatments to decrease healing time and reduce the development of complications during the extended recovery from fracture healing in the elderly.
Core tip: Bone fractures in the elderly are a significant issue, due to the prevalence of the problem, the difficulty of treatment, and the severe consequences of the extended healing period. The delay in fracture healing with advanced age has been attributed to both the decreased number and function of mesenchymal stem cells that regenerate the bone and the inferior performance of endothelial progenitor cells that direct angiogenesis. Some suggested avenues for potential treatments include cellular therapies, pharmacological agents, treatments targeting age-related molecular mechanisms, and physical therapeutics.