The Role of Sex Differences in Bone Health and Healing

Simple Summary Fracture healing is a complex process that includes a framework of events triggered by tissue injury. Clinical experience with bone healing revealed a series of cellular and biochemical actors encompassing the repair mechanisms in human beings. However, the different responses of individuals in this scenario are still a matter of debate. We analyze herein in some detail the disparity between men and women in this process. Based on the literature, we suggest that different mechanisms could underlie bone healing in men and women and that the role of estrogen could be pivotal in delayed fracture repair observed in women. Fracture healing is a long-term and complex process influenced by a huge variety of factors. Among these, there is a sex/gender disparity. Based on significant differences observed in the outcome of bone healing in males and females, in the present review, we report the main findings, hypotheses and pitfalls that could lead to these differences. In particular, the role of sex hormones and inflammation has been reported to have a role in the observed less efficient bone healing in females in comparison with that observed in males. In addition, estrogen-induced cellular processes such as autophagic cell cycle impairment and molecular signals suppressing cell cycle progression seem also to play a role in female fracture healing delay. In conclusion, it seems conceivable that a complex framework of events could contribute to the female bias in bone healing, and we suggest that a reappraisal of the compelling factors could contribute to the mitigation of sex/gender disparity and improve bone healing outcomes.