Cigarette Smoke Exposure Impairs Fracture Healing in a Rat Model: Preferential Impairment of Endochondral Over Membranous Healing

J Biomech Eng. 2025 Jan 1;147(1):011005. doi: 10.1115/1.4066796.

Abstract

Background: Cigarette smoking adversely affects fracture repair, causing delayed healing or nonunion rates twice those seen in nonsmokers.

Purpose: We sought to investigate if cigarette smoke differentially affects intramembranous and endochondral healing of fractures. We hypothesize that healing via endochondral ossification will be preferentially impaired compared to intramembranous ossification.

Methods: We utilized a bilateral femur fracture model in Sprague Dawley rats to examine effects of cigarette smoke exposure on healing of femur fractures, treated with either locked intramedullary nail or compression plating to induce endochondral and membranous ossification, respectively. Animals were exposed to tobacco smoke 30 days before and after surgery; evaluations included radiographs, histomorphometry, and micro-CT at 10 days, 1, 3, and 6 months postoperation, and biomechanical testing at 3 and 6 months.

Results: Sixty-eight animals were randomized to control or exposure (two died perioperatively); 89% of femora achieved union when harvested at 3 or 6 months. Smoke exposure delayed cartilaginous callus formation and bone maturation in nailed fractures compared to plated fractures and controls in the same animals. Plated fractures in exposed animals exhibited little cartilage callus and healed like control animals. At 3 months, plated fractures were stiffer and stronger than nailed fractures in both groups. These differences vanished by 6 months.

Conclusions: Plated fractures healed more rapidly and completely than nailed fractures under both control and smoke-exposed conditions.

Clinical relevance: Using compression plating instead of IM nailing for closed long bone fractures may lead to better outcomes in patients who smoke compared to current results with nailing.

Keywords: endochondral; fracture; intramembranous ossification; nails; plate; smoke exposure.

MeSH terms

  • Animals
  • Biomechanical Phenomena
  • Disease Models, Animal
  • Femoral Fractures* / pathology
  • Femoral Fractures* / physiopathology
  • Fracture Healing*
  • Male
  • Osteogenesis / drug effects
  • Rats
  • Rats, Sprague-Dawley*
  • Smoke / adverse effects

Substances

  • Smoke