Zoledronic acid enhances bone-implant osseointegration more than alendronate and strontium ranelate in ovariectomized rats

Osteoporos Int. 2013 Jul;24(7):2115-21. doi: 10.1007/s00198-013-2288-7. Epub 2013 Feb 7.

Abstract

This study was designed to compare the effects of alendronate (ALN), strontium ranelate (SR), and zoledronic acid (ZOL) on bone-implant osseointegration in ovariectomized rats. Histological examination and biomechanical tests show that ZOL, ALN, and SR enhance bone-implant osseointegration; ALN and SR have similar effects, while ZOL enhances bone-implant osseointegration more than ALN and SR INTRODUCTION: This study aims to compare the effects of ALN, SR, and ZOL on bone-implant osseointegration in ovariectomized rats.

Methods: Sixty female Sprague-Dawley rats were included in this study. Of them, 48 rats were ovariectomized (OVX) and assigned to four groups: OVX (OVX + Veh), ALN (OVX + ALN), SR (OVX + SR), and ZOL (OVX + ZOL). And another 12 rats were sham-operated as a control group (Sham). Four weeks after ovariectomy, HA-coated titanium implants were inserted into the tibias bilaterally in all rats. Then the rats in groups ALN, SR, and ZOL were systemically administrated with alendronate (7 mg/kg/week, orally), strontium ranelate (500 mg/kg/day, orally), or a single injection of zoledronic acid (0.1 mg/kg, iv), respectively. Twelve weeks after implantation, all rats were sacrificed to get the femurs and tibias. Histological examination and biomechanical tests were used to evaluate bone-implant osseointegration in all groups.

Results: ALN, SR, and ZOL significantly increased distal femoral BMD when compared with group OVX; ZOL increased BMD significantly more than ALN and SR (P < 0.05). Significant increase of bone-to-implant contact and peri-implant bone fraction were observed in groups ALN, SR, and ZOL when compared with group OVX (P < 0.05). Groups ALN and SR were inferior to groups ZOL and Sham (P < 0.05) in bone-to-implant contact and peri-implant bone fraction. Similar results were found in biomechanical testing (max pushout force).

Conclusions: In rats losing bone rapidly after ovariectomy, systemic administration of ZOL, ALN, and SR causes better bone-implant osseointegration when compared to OVX; ALN and SR have similar positive effects on osseointegration, while ZOL, that was given in a dose with more positive BMD effect than that of ALN or SR, causes better osseointegration than either ALN or SR.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alendronate / pharmacology
  • Animals
  • Bone Density / drug effects
  • Bone Density / physiology
  • Bone Density Conservation Agents / pharmacology*
  • Diphosphonates / pharmacology*
  • Drug Evaluation, Preclinical / methods
  • Female
  • Femur / drug effects
  • Femur / physiopathology
  • Humans
  • Imidazoles / pharmacology*
  • Materials Testing / methods
  • Orthopedic Fixation Devices
  • Osseointegration / drug effects*
  • Osseointegration / physiology
  • Osteoporosis, Postmenopausal / drug therapy
  • Osteoporosis, Postmenopausal / physiopathology*
  • Ovariectomy
  • Prostheses and Implants*
  • Rats
  • Stress, Mechanical
  • Thiophenes / pharmacology
  • Tibia / drug effects
  • Tibia / pathology
  • Tibia / surgery
  • Titanium
  • Zoledronic Acid

Substances

  • Bone Density Conservation Agents
  • Diphosphonates
  • Imidazoles
  • Thiophenes
  • strontium ranelate
  • Zoledronic Acid
  • Titanium
  • Alendronate