Alendronate enhances osseointegration in a murine implant model.

TitleAlendronate enhances osseointegration in a murine implant model.
Publication TypeJournal Article
Year of Publication2021
AuthorsVertesich K, Sosa BR, Niu Y, Ji G, Suhardi V, Turajane K, Mun S, Xu R, Windhager R, Park-Min KHyun, Greenblatt MB, Bostrom MP, Yang X
JournalJ Orthop Res
Volume39
Issue4
Pagination719-726
Date Published2021 04
ISSN1554-527X
KeywordsAlendronate, Animals, Arthroplasty, Replacement, Bone Density, Bone Density Conservation Agents, Bone Substitutes, Bone-Implant Interface, Diphosphonates, Female, Mice, Mice, Inbred C57BL, Microscopy, Fluorescence, Osseointegration, Osteoclasts, Osteogenesis, Postoperative Period, Stress, Mechanical, Tibia, X-Ray Microtomography
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.

DOI10.1002/jor.24853
Alternate JournalJ Orthop Res
PubMed ID32915488
Grant ListDP5 OD021351 / OD / NIH HHS / United States
UL1 TR000457 / TR / NCATS NIH HHS / United States
R01 AR075585 / RG / CSR NIH HHS / United States
DP5OD021351 / RG / CSR NIH HHS / United States
Related Faculty: 
Matthew B. Greenblatt, M.D., Ph.D.

Pathology & Laboratory Medicine 1300 York Avenue New York, NY 10065 Phone: (212) 746-6464
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