Assessment of the Impact of Zoledronic Acid on Ovariectomized Osteoporosis Model Using Micro-CT Scanning

PLoS One. 2015 Jul 6;10(7):e0132104. doi: 10.1371/journal.pone.0132104. eCollection 2015.

Abstract

Purpose/objective: Prompted by preliminary findings, this study was conducted to investigate the impact of zoledronic acid on the cancellous bone microstructure and its effect on the level of β-catenin in a mouse model of postmenopausal osteoporosis.

Methods and materials: 96 8-week-old specific-pathogen-free C57BL/6 mice were randomly divided into 4 groups (24 per group): a sham group, an ovariectomized osteoporosis model group, an estradiol-treated group, and a zoledronic acid-treated group. Five months after surgery, the third lumbar vertebra and left femur of the animals were dissected and scanned using micro-computed tomography (micro-CT) to acquire three-dimensional imagery of their cancellous bone microstructure. The impact of ovariectomy, the effect of estradiol, and the effect of zoledronic acid intervention on cancellous bone microstructure, as well as on the expression of β-catenin, were evaluated.

Results: The estradiol-treated and the zoledronic acid-treated group exhibited a significant increase in the bone volume fraction, trabecular number, trabecular thickness, bone surface to bone volume ratio (BS/BV), and β-catenin expression, when compared with those of the control group (P <0.01). In contrast, the structure model index, trabecular separation, and BS/BV were significantly lower compared with those of the model group (P <0.01). No differences were observed in the above parameters between animals of the zoledronic acid-treated and the estradiol-treated group.

Conclusion: These results suggest that increased β-catenin expression may be the mechanism underlying zoledronic acid-related improvement in the cancellous bone microstructure in ovariectomized mice. Our findings provide a scientific rationale for using zoledronic acid as a therapeutic intervention to prevent bone loss in post-menopausal women.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Diphosphonates / pharmacology*
  • Disease Models, Animal
  • Estradiol / pharmacology
  • Female
  • Humans
  • Imidazoles / pharmacology*
  • Mice
  • Osteoporosis, Postmenopausal / diagnostic imaging
  • Osteoporosis, Postmenopausal / drug therapy*
  • Osteoporosis, Postmenopausal / metabolism
  • Osteoporosis, Postmenopausal / pathology
  • Ovariectomy
  • X-Ray Microtomography
  • Zoledronic Acid

Substances

  • Diphosphonates
  • Imidazoles
  • Estradiol
  • Zoledronic Acid

Grants and funding

This research was funded by the National Natural Science Foundation of China (Project Number: 81403257 to Bo Shuai, 81473492 to Lin Shen, and 81072493 to Ping Yan Yang) (http://www.nsfc.gov.cn/publish/portal0/tab117/).