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Clopidogrel Influences Fracture Healing Under Ischemic Conditions.

Sebastian Schreiber1, Janine Stutz1, Lukas Keller1

  • 1Department of Trauma, Hand and Reconstructive Surgery, Saarland University, D-66421 Homburg, Germany.

Biomedicines
|September 27, 2025
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Summary

Clopidogrel may hinder fracture healing in patients with tissue ischemia. This study found impaired bone healing and altered gene expression in mice treated with clopidogrel under ischemic conditions.

Keywords:
BMP-4CD31clopidogrelfracture healingischemiamouse

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Area of Science:

  • Orthopedics
  • Pharmacology
  • Regenerative Medicine

Background:

  • Clopidogrel is frequently used in fracture patients with comorbidities.
  • Existing research suggests clopidogrel inhibits osteoblast proliferation and bone formation.
  • The effect of clopidogrel on fracture healing under ischemic conditions remains unclear.

Purpose of the Study:

  • To investigate the impact of clopidogrel on fracture healing in a murine model of limb ischemia.
  • To assess whether clopidogrel affects bone healing under compromised blood supply.

Main Methods:

  • A murine model of femoral fracture with induced limb ischemia was established.
  • Animals received daily oral administration of clopidogrel (3 mg/kg) or vehicle.
  • Bone healing was evaluated using biomechanical testing, radiography, histomorphometry, and Western blot analysis at 2 and 5 weeks post-fracture.

Main Results:

  • Clopidogrel treatment resulted in no improvement in biomechanical stiffness of fractured femurs compared to controls.
  • Histomorphometric analysis revealed reduced bone bridging and increased connective tissue in the fracture callus of clopidogrel-treated mice.
  • Western blot analysis showed decreased expression of bone morphogenetic protein-4 (BMP-4) and increased expression of CD31 in the clopidogrel group.

Conclusions:

  • Clopidogrel impairs fracture healing in the presence of ischemia.
  • This impairment is linked to altered expression of angiogenic (CD31) and osteogenic (BMP-4) markers.
  • Clopidogrel use may be contraindicated in fracture patients experiencing tissue ischemia.