Melatonin promotes fracture healing at pharmacological doses on the early phase in perforating fracture model

Abstract

Fracture has considerably improved through development of therapeutic approaches, although there showed which delayed recovery, nonunion, and complications after fracture injuries. Numerous studies reported that melatonin has a positive effect for bone formation in vitro. The aim of this study was to determine whether melatonin has an effect on fracture healing in femur perforating fracture model. SD rats (8‐week old) were randomly divided into fracture (Con), fracture+5 mg/kg melatonin treatment (LMT), and fracture+10 mg/kg melatonin treatment (HMT). After perforating fracture using micro drill, the rats were treated twice daily with melatonin at 7:00 and 19:00 during 21 days. Comparison of Con, LMT is significantly augmented the bone formation related gene expression, such as RUNX2, ALP, COL1, and DMP1 (p<.01), and HMT significantly showed the increase of ALP (p<.05) and DMP1 (p<.01) in the early stages. Micro CT scan analysis, both melatonin groups showed a significant increase of bone mineral density compare to Con in the early stage (p<.01). In histology, LMT considerably revealed the recovery of cortical area of damaged bone. Whereas, HMT showed a delay of recovery phase compared to LMT and Con. Based on these results, we suggest that melatonin has a therapeutic effect in the early stage of fracture healing. Nonetheless, excessive or long‐term treatment might be lead to a negative effect to fracture healing.