Researchers identified apolipoprotein E (ApoE) as a key mechanism behind age-related bone healing impairment. In 24-month-old mice with hepatic ApoE deletion, circulating ApoE dropped 95% and fracture healing significantly improved. The protein operates through a specific molecular pathway: ApoE binds to the Lrp4 receptor on bone-forming cells, suppressing Wnt/β-catenin signaling that drives osteoblast differentiation. This mechanism was confirmed in both mouse and human bone cells. Most promising for clinical translation, an ApoE-neutralizing antibody administered three days post-fracture increased bone formation by 35% in aged mice. This discovery reveals an unexpected liver-bone communication axis that deteriorates with aging. While previous research focused on local bone factors or systemic hormones, this work implicates hepatic protein secretion as a major contributor to declining bone repair capacity. The therapeutic window appears favorable since treatment began after injury rather than requiring pre-treatment. However, the safety profile of sustained ApoE inhibition remains unknown, particularly given ApoE's established roles in cholesterol transport and cardiovascular health. The approach could benefit elderly patients facing prolonged recovery times, though human trials must address potential lipid metabolism disruption.