Alendronate enhances osseointegration in a murine implant model

J Orthop Res. 2021 Apr;39(4):719-726. doi: 10.1002/jor.24853. Epub 2020 Sep 19.

Abstract

Administration of bisphosphonates following total joint arthroplasty might be beneficial to reduce aseptic loosening. However, their effects on peri-implant bone formation and bone-implant interface strength have not been investigated yet. We used a physiologically loaded mouse implant model to investigate the short-term effects of postoperative systemic alendronate on osseointegration. A titanium implant with a rough surface was inserted in the proximal tibiae of 17-week-old female C57BL/6 mice (n = 44). Postimplantation mice were given alendronate (73 μg/kg/days, n = 22) or vehicle (n = 22) 5 days/week. At 7- and 14-day postimplantation, histology and histomorphometry were conducted. At 28 days, microcomputed tomography and biomechanical testing were performed (n = 10/group). Postoperative alendronate treatment enhanced osseointegration, increasing maximum pullout load by 45% (p < .001) from 19.1 ± 4.5 N in the control mice to 27.6 ± 4.9 N in the treated mice, at day 28 postimplantation. Alendronate treatment increased the bone volume fraction by 139% (p < .001) in the region distal to the implant and 60% (p < .05) in the peri-implant region. At 14-day postimplantation, alendronate treatment decreased the number of osteoclasts per bone perimeter (p < .05) and increased bone volume fraction (p < .01) when compared with the control group. Postimplantation, short-term alendronate treatment enhanced osseointegration as demonstrated by increased bone mass, trabecular bone thickness, and maximum pullout load. Alendronate decreased peri-implant osteoclasts while preserving peri-implant osteoblasts and endothelial cells, in turn, increasing bone volume fraction. This data supports the postoperative clinical use of bisphosphonates, especially in patients with high risks of aseptic loosening.

Keywords: alendronate; aseptic loosening; bisphosphonates; implant model; osseointegration.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alendronate / pharmacology*
  • Animals
  • Arthroplasty, Replacement*
  • Bone Density / drug effects
  • Bone Density Conservation Agents / pharmacology*
  • Bone Substitutes
  • Bone-Implant Interface
  • Diphosphonates / pharmacology
  • Female
  • Mice
  • Mice, Inbred C57BL
  • Microscopy, Fluorescence
  • Osseointegration / drug effects*
  • Osteoclasts / drug effects
  • Osteogenesis / drug effects
  • Postoperative Period
  • Stress, Mechanical
  • Tibia / surgery
  • X-Ray Microtomography

Substances

  • Bone Density Conservation Agents
  • Bone Substitutes
  • Diphosphonates
  • Alendronate