The effect of pharmacological treatment in combination with vitamin K on healing in an experimental rat model of osteoporosis

Jt Dis Relat Surg. 2023 Apr 27;34(2):356-364. doi: 10.52312/jdrs.2023.911.

Abstract

Objectives: This study aims to compare the effects of teriparatide, zoledronic acid, and their combination therapy with vitamin K on osteoporotic rats.

Materials and methods: We divided a total of 50 female Sprague-Dawley rats into five groups: A (the control group), B and D (the teriparatide group), and C and E (the zoledronic acid group). Following ovariectomy and subcutaneous heparin administration at a dose of 2 IU/kg for four weeks, osteoporosis was created. Groups A, B, and C were fed with standard feed, while Groups D and E were fed with vitamin K-rich feed. After four weeks of treatment, sacrification was performed. The right and left femurs were separated for histopathological and biomechanical evaluation, respectively. For histopathological evaluation, the femurs were decalcified, and the sections were stained with hematoxylin-eosin and evaluated under a light microscope. Fracture healing was evaluated using the classification system as described previously. For biomechanical evaluation, the 3-point stress test and torsion stress test were applied to 10 femurs from each group.

Results: Groups B-E were histopathologically and biomechanically superior to Group A in fracture healing of osteoporotic rats; however, it was not statistically significant (p>0.05). The group that received additional vitamin K was histopathologically and biomechanically superior to the group which was fed with standard feed, although it was not statistically significant (p>0.05).

Conclusion: Our study results indicated that both teriparatide and zoledronic acid had beneficial effects on osteoporotic fractures with comparable histological and biochemical results. Vitamin K promoted teriparatide and zoledronic acid treatment on osteoporotic fracture healing. Based on these findings, combination therapies may yield the most optimal results in biomechanical and histological examinations.

MeSH terms

  • Animals
  • Bone Density Conservation Agents* / pharmacology
  • Bone Density Conservation Agents* / therapeutic use
  • Female
  • Fracture Healing
  • Osteoporosis* / drug therapy
  • Osteoporotic Fractures*
  • Rats
  • Rats, Sprague-Dawley
  • Teriparatide / pharmacology
  • Teriparatide / therapeutic use
  • Vitamin K / pharmacology
  • Vitamin K / therapeutic use
  • Zoledronic Acid / pharmacology
  • Zoledronic Acid / therapeutic use

Substances

  • Zoledronic Acid
  • Teriparatide
  • Bone Density Conservation Agents
  • Vitamin K