Effects of Aging on Fracture Healing

Abstract

Purpose of review: This review summarizes research on the physiological changes that occur with aging and the resulting effects on fracture healing.

Recent findings: Aging affects the inflammatory response during fracture healing through senescence of the immune response and increased systemic pro-inflammatory status. Important cells of the inflammatory response, macrophages, T cells, mesenchymal stem cells, have demonstrated intrinsic age-related changes that could impact fracture healing. Additionally, vascularization and angiogenesis are impaired in fracture healing of the elderly. Finally, osteochondral cells and their progenitors demonstrate decreased activity and quantity within the callus. Age-related changes affect many of the biologic processes involved in fracture healing. However, the contributions of such changes do not fully explain the poorer healing outcomes and increased morbidity reported in elderly patients. Future research should address this gap in understanding in order to provide improved and more directed treatment options for the elderly population.

Keywords: Elderly; Fracture healing; Inflamm-aging; Inflammatory response; Senescence.

Fig. 1

The effect of age on the cellular contribution to fracture healing. Stem cells and immune cells involved in fracture healing demonstrate age-related changes that may negatively affect fracture healing. Osteochondral stem cells arise from the periosteum and bone marrow and demonstrate decreased quantity, increased oxidative damage, and decreased osteoblastic and chondrogenic differentiation potential with age. T-cells contribute to fracture healing and production and maturation of T cells is negatively affected by age-related changes to the bone marrow hematopoietic compartment and to the thymus. Macrophages are important regulators of inflammation during fracture healing. Aged macrophages demonstrate decreased proliferation and increased activation that may contribute to the poorer healing outcomes associated with aged macrophages compared to young. Finally, adequate vascularization is required for successful fracture healing. Aged animals demonstrate decreased vascular density within the callus which is associated with decreased levels of key angiogenic factors required for healing

Fig. 2

The effects of inflammatory response perturbation on the stages of fracture healing. a Fracture healing follows three general stages of inflammation, proliferation, and remodeling. The initial inflammatory response is tightly regulated and crucial in initiating the subsequent stages of healing. b Systemic conditions, including increased age, have an effect on inflammation and may result in differential inflammatory responses during fracture healing. Senescence of the inflammatory response results in a decreased and limited inflammatory response (blue curve) that may result in inadequate activation of the proceeding healing stages. An exaggerated and sustained response (orange and red curves) can result from inadequate resolution of the response and may negatively affect the proceeding stages. An increased basal level of inflammation (red curve) is proposed to occur with inflamm-aging and would have possible negative effects throughout the healing process