The influence of adrenoceptor blocker treatment on fracture healing in osteoporotic and non-osteoporotic bone

Fracture healing is a highly dynamic process that involves inflammation, cell recruitment, angiogenesis, and subsequent bone formation and remodeling. Increasing evidence suggests the pivotal role of adrenergic signaling in musculoskeletal repair and bone-related diseases such as osteoporosis. Furthermore, impaired fracture healing in osteoporotic female mice might be attributed to an overshooting immune response with increasing numbers of neutrophils found in the early fracture hematoma. Earlier studies showed that an unspecific blockade of the β-adrenoceptor with propranolol reduces the number of neutrophils in the fracture hematoma in male mice, which might also help alleviate the overshooting immune response in female osteoporotic mice. In this study, we hypothesized that adrenoceptor blocker treatment in the early inflammatory phase of fracture healing rescues the excessive immune response in osteoporotic female mice and thereby improves fracture healing. However, our results indicate that an early blockade of adrenergic receptors does not improve fracture healing in osteoporotic and non-osteoporotic mice. In contrast to earlier studies with male mice, beta blockade (propranolol and butoxamine) in female non-osteoporotic mice increased the number of neutrophils in the early fracture hematoma, indicating an elevated immune response and a sex-dependent effect of adrenoceptor blocker treatment.