Estrogen deficiency impedes fracture healing despite eliminating the excessive absorption of the posterior callus in a semi-fixed distal tibial fracture mouse model

BMC Musculoskelet Disord. 2023 Oct 10;24(1):803. doi: 10.1186/s12891-023-06929-2.

Abstract

Background: Treatment of distal tibial fractures is a challenge due to their specific anatomical location. However, there is no appropriate mouse model to simulate a clinical distal tibial fracture for basic research. The aim of this investigation was to evaluate the feasibility of simulating a clinical fracture of the distal tibia of mice and to investigate the effect of ovariectomy (OVX)-induced osteoporosis on fracture healing in this model.

Methods: Sixty female 8-week-old C57BL/6 mice were randomly divided into two groups, either sham or OVX. A semi-fixation distal tibia fracture was established in the right tibia after 8 weeks of OVX. The right tibias were collected at 7, 14, 21, and 28 days post fracture.

Results: In the semi-fixation distal tibia fracture model, the posterior callus in the sham group showed excessive bone resorption and lower bone mass phenotype compared with the anterior site; a similar trend was not found in the OVX group. At 28 days post fracture, the posterior callus was more mineralized than the anterior callus in the OVX group. Although the fracture healing of the sham group showed a special phenotype in this mode, the progress and quality of fracture healing were still better than those of the OVX group.

Conclusion: A semi-fixed distal tibial closed fracture mouse model was successfully established. In this model, excess bone resorption of the posterior callus impaired normal fracture healing, but not in OVX-induced osteoporotic bone. Although the stress shielding effect was not observed in the OVX group, impaired bone healing caused by OVX was still present. Our results suggest that this fracture model may have potential for studies on distal tibial fractures and stress shielding.

Keywords: Distal tibia; Fracture healing; Mouse model; Osteoporosis.

MeSH terms

  • Animals
  • Bone Resorption*
  • Bony Callus / diagnostic imaging
  • Disease Models, Animal
  • Estrogens
  • Female
  • Fracture Healing
  • Humans
  • Mice
  • Mice, Inbred C57BL
  • Ovariectomy / adverse effects
  • Rats
  • Rats, Sprague-Dawley
  • Tibial Fractures* / drug therapy

Substances

  • Estrogens