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Poor histological healing of a femoral fracture following 12 months of oestrogen deficiency in rats

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Abstract

Summary

Fractures in post-menopausal osteoporosis cause significant morbidity; however, animal models for post-menopausal fracture healing lack the effect of ageing. Therefore, we developed a model using aged animals with chronic oestrogen deficiency, which demonstrates inferior fracture repair (decreased healing histologically, bone mineral density and content and strength). This novel model may help develop molecular strategies for osteoporotic fracture repair.

Introduction

The femur is susceptible to damage by both systemic conditions such as osteoporosis and locally by traumatic injury. The capacity for fracture repair decreases with age, while the risk of fracture increases. As studies of osteoporotic fracture healing in rats traditionally use a period of 3 months or less of oestrogen deficiency prior to fracturing, we aimed to establish a osteoporosis model in rats with chronic oestrogen deficiency by 12 months to better mimic human female osteoporosis.

Methods

Seventy female Sprague–Dawley rats (10 weeks old) were ovariectomised or sham operated and housed for 12 months. The right femur was fractured by way of an open osteotomy and fixed with an intramedullary Kirschner wire. Animals were sacrificed at 1, 3 and 6 weeks for radiography, dual-energy X-ray absorptiometry, tensile testing and histology.

Results

Bone mineral density and bone mineral content were lower by 60 and 63 %, respectively, (p < 0.05) in the bilaterally ovariectomized (OVX) groups than those in the sham groups at 6 weeks in the right fractured femurs. Maximum breaking force of the OVX group was lower than that of the sham group, with the greatest difference seen at 6 weeks following osteotomy. Histologically, the OVX groups demonstrated a delay in cellular differentiation within the fracture callus and the presence of bone resorption. The sham animals had a superior histological healing pattern with an Allen score of 4 at 6 weeks compared to a score of 1 for the OVX groups (p < 0.01).

Conclusions

Long-term ovariectomy has a deleterious effect on fracture healing in a rodent model.

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Acknowledgments

We would like to acknowledge Julia Janssen of St. George Hospital for doing the DEXA scans for this study.

Conflicts of interest

None.

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Authors and Affiliations

  1. Surgical & Orthopaedic Research Laboratory, Prince of Wales Clinical School, University of New South Wales, Level 1, Clinical Sciences Bldg, Barker Street, Randwick, NSW, 2031, Sydney, Australia

    R. A. Oliver, Y. Yu, G. Yee, A. K. Low & W. R. Walsh

  2. Department of Orthopaedic Surgery, St. George Hospital, University of New South Wales, Kogarah, Sydney, Australia

    A. D. Diwan

Authors
  1. R. A. Oliver
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  2. Y. Yu
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  3. G. Yee
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  4. A. K. Low
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  5. A. D. Diwan
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  6. W. R. Walsh
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Corresponding author

Correspondence to R. A. Oliver.

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Oliver, R.A., Yu, Y., Yee, G. et al. Poor histological healing of a femoral fracture following 12 months of oestrogen deficiency in rats. Osteoporos Int 24, 2581–2589 (2013). https://doi.org/10.1007/s00198-013-2345-2

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  • DOI: https://doi.org/10.1007/s00198-013-2345-2

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