Local ZnCl2 accelerates fracture healing

J Orthop Res. 2014 Jun;32(6):834-41. doi: 10.1002/jor.22593. Epub 2014 Feb 26.


This study evaluated the effect of local zinc chloride (ZnCl2 ), an insulin mimetic agent, upon the early and late parameters of fracture healing in rats using a standard femur fracture model. Mechanical testing, radiographic scoring, histomorphometry, qualitative histological scoring, PCNA immunohistochemistry, and local growth factor analysis were performed. Fractures treated with local ZnCl2 possessed significantly increased mechanical properties compared to controls at 4 weeks post fracture. The radiographic scoring analysis showed increased cortical bridging at 4 weeks in the 1.0 (p=0.0015) and 3.0 (p<0.0001) mg/kg ZnCl2 treated groups. Histomorphometry of the fracture callus at day 7 showed 177% increase (p=0.036) in percent cartilage and 133% increase (p=0.002) in percent mineralized tissue with local ZnCl2 treatment compared to controls. Qualitative histological scoring showed a 2.1× higher value at day 7 in the ZnCl2 treated group compared to control (p = 0.004). Cell proliferation and growth factors, VEGF and IGF-I, within fracture calluses treated with local ZnCl2 were increased at day 7. The results suggest local administration of ZnCl2 increases cell proliferation, causing increased growth factor production which yields improved chondrogenesis and endochondral ossification. Ultimately, these events lead to accelerated fracture healing as early as 4 weeks post fracture.

Keywords: bone healing; fracture healing; insulin mimetic; rat; zinc chloride.

Publication types

  • Evaluation Study

MeSH terms

  • Animals
  • Bony Callus / drug effects*
  • Cell Proliferation
  • Chlorides / therapeutic use*
  • Chondrogenesis
  • Femoral Fractures / drug therapy*
  • Femoral Fractures / pathology
  • Femur / drug effects
  • Fracture Healing / drug effects*
  • Insulin-Like Growth Factor I / biosynthesis
  • Male
  • Proliferating Cell Nuclear Antigen / biosynthesis
  • Rats
  • Rats, Inbred BB
  • Vascular Endothelial Growth Factor A / biosynthesis
  • Zinc Compounds / therapeutic use*


  • Chlorides
  • Proliferating Cell Nuclear Antigen
  • Vascular Endothelial Growth Factor A
  • Zinc Compounds
  • insulin-like growth factor-1, rat
  • vascular endothelial growth factor A, rat
  • Insulin-Like Growth Factor I
  • zinc chloride