Skip to main content
Erschienen in: Clinical Orthopaedics and Related Research® 2/2014

01.02.2014 | Symposium: 2013 Hip Society Proceedings

Local Alendronic Acid Elution Increases Net Periimplant Bone Formation: A Micro-CT Analysis

verfasst von: J. Dennis Bobyn, PhD, Rebecca Thompson, MEng, Letitia Lim, MD, Jenny Ann Pura, BSc, Kristian Bobyn, BA, Michael Tanzer, MD

Erschienen in: Clinical Orthopaedics and Related Research® | Ausgabe 2/2014

Einloggen, um Zugang zu erhalten

Abstract

Background

Fixation of cementless orthopaedic implants is not always achieved, particularly in challenging scenarios such as revision surgery, trauma, and tumor reconstruction. An adjunct therapy for improving implant fixation would improve the reliability and durability of certain reconstructive procedures.

Questions/purposes

The purpose of this study was to determine the effect of local elution of the bisphosphonate alendronic acid on bone formation around porous titanium implants in an animal model.

Methods

Porous-coated cylindrical rods were coated with either 0.2 mg or 1.0 mg alendronic acid before bilateral surgical implantation into the femoral intramedullary canals of 10 experimental dogs. Twelve weeks after surgery, the femora were harvested and scanned with micro-CT to quantify the percentage volume of bone within the immediate periimplant space. Four femora from two dogs were also processed for undecalcified thin-section histology and analysis with backscattered scanning electron microscopy. Three histologic sections from each of these four femora were anatomically matched with transverse micro-CT sections to enable direct comparison of the area fraction of bone within the periimplant space.

Results

Compared with paired controls, micro-CT analysis showed that local elution of alendronic acid increased periimplant bone at both doses of 0.2 mg (+52%, p = 0.01) and 1.0 mg (+152%, p = 0.004) with 1.0 mg resulting in a 2.9-fold greater mean relative increase compared with 0.2 mg (p = 0.002). Micro-CT measurements of periimplant bone formation correlated very strongly with the backscattered scanning electron microscopy measurements (R = 0.965, p < 0.001).

Conclusions

Local elution of alendronic acid causes a dose-dependent net increase in periimplant bone formation in an animal model.

Clinical Relevance

This concept has potential to improve the biologic fixation of porous reconstructive implants.

Level of Evidence

Level II, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence.
Literatur
1.
Zurück zum Zitat Arabmotlagh M, Pilz M, Warzecha J, Rauschmann M. Changes of femoral periprosthetic bone mineral density 6 years after treatment with alendronate following total hip arthroplasty. J Orthop Res. 2009;27:183–188.PubMedCrossRef Arabmotlagh M, Pilz M, Warzecha J, Rauschmann M. Changes of femoral periprosthetic bone mineral density 6 years after treatment with alendronate following total hip arthroplasty. J Orthop Res. 2009;27:183–188.PubMedCrossRef
2.
Zurück zum Zitat Bhandari M, Bajammal S, Guyatt GH, Griffith L, Busse JW, Schünemann H, Einhorn TA. . Effect of bisphosphonates on periprosthetic bone mineral density after total joint arthroplasty. A meta-analysis. J Bone Joint Surg Am. 2005;87:293–301.PubMedCrossRef Bhandari M, Bajammal S, Guyatt GH, Griffith L, Busse JW, Schünemann H, Einhorn TA. . Effect of bisphosphonates on periprosthetic bone mineral density after total joint arthroplasty. A meta-analysis. J Bone Joint Surg Am. 2005;87:293–301.PubMedCrossRef
3.
Zurück zum Zitat Bobyn JD, Hacking SA, Krygier JJ, Harvey EJ, Little DG, Tanzer M. Zoledronic acid causes enhancement of bone growth into porous implants. J Bone Joint Surg Br. 2005;87:416–420.PubMedCrossRef Bobyn JD, Hacking SA, Krygier JJ, Harvey EJ, Little DG, Tanzer M. Zoledronic acid causes enhancement of bone growth into porous implants. J Bone Joint Surg Br. 2005;87:416–420.PubMedCrossRef
4.
Zurück zum Zitat Bobyn JD, McKenzie K, Karabasz D, Krygier JJ, Tanzer M. Locally delivered bisphosphonate for enhancement of bone formation and implant fixation. J Bone Joint Surg. 2009;91(Suppl 6):23–31.PubMedCrossRef Bobyn JD, McKenzie K, Karabasz D, Krygier JJ, Tanzer M. Locally delivered bisphosphonate for enhancement of bone formation and implant fixation. J Bone Joint Surg. 2009;91(Suppl 6):23–31.PubMedCrossRef
5.
Zurück zum Zitat Cook RE, Jenkins PJ, Walmsley PJ, Patton JT, Robinson CM. Risk factors for periprosthetic fractures of the hip: a survivorship analysis. Clin Orthop Relat Res. 2008;466:1652–1656.PubMedCrossRef Cook RE, Jenkins PJ, Walmsley PJ, Patton JT, Robinson CM. Risk factors for periprosthetic fractures of the hip: a survivorship analysis. Clin Orthop Relat Res. 2008;466:1652–1656.PubMedCrossRef
6.
Zurück zum Zitat Friedl G, Radl R, Stihsen C, Rehak P, Aigner R, Windhager R. The effect of a single infusion of zoledronic acid on early implant migration in total hip arthroplasty. A randomized, double-blind, controlled trial. J Bone Joint Surg Am. 2009;91:274–281.PubMedCrossRef Friedl G, Radl R, Stihsen C, Rehak P, Aigner R, Windhager R. The effect of a single infusion of zoledronic acid on early implant migration in total hip arthroplasty. A randomized, double-blind, controlled trial. J Bone Joint Surg Am. 2009;91:274–281.PubMedCrossRef
7.
Zurück zum Zitat Gao Y, Zou S, Liu X, Bao C, Hu J. The effect of surface immobilized bisphosphonates on the fixation of hydroxyapatite-coated titanium implants in ovariectomized rats. Biomaterials. 2009;30:1790–1796.PubMedCrossRef Gao Y, Zou S, Liu X, Bao C, Hu J. The effect of surface immobilized bisphosphonates on the fixation of hydroxyapatite-coated titanium implants in ovariectomized rats. Biomaterials. 2009;30:1790–1796.PubMedCrossRef
8.
Zurück zum Zitat Garbuz DS, Hu Y, Kim WY, Duan K, Masri BA, Oxland TR, Burt H, Wang R, Duncan CP. Enhanced gap filling and osteoconduction associated with alendronate-calcium phosphate-coated porous tantalum. J Bone Joint Surg Am. 2008;90:1090–1100.PubMedCrossRef Garbuz DS, Hu Y, Kim WY, Duan K, Masri BA, Oxland TR, Burt H, Wang R, Duncan CP. Enhanced gap filling and osteoconduction associated with alendronate-calcium phosphate-coated porous tantalum. J Bone Joint Surg Am. 2008;90:1090–1100.PubMedCrossRef
9.
Zurück zum Zitat Garcia-Moreno C, Serrano S, Nacher M, Farré M, Díez A, Mariñoso ML, Carbonell J, Mellibovsky L, Nogués X, Ballester J, Aubía J. Effect of alendronate on cultured normal human osteoblasts. Bone. 1998;22:233–239.PubMedCrossRef Garcia-Moreno C, Serrano S, Nacher M, Farré M, Díez A, Mariñoso ML, Carbonell J, Mellibovsky L, Nogués X, Ballester J, Aubía J. Effect of alendronate on cultured normal human osteoblasts. Bone. 1998;22:233–239.PubMedCrossRef
10.
Zurück zum Zitat Goodship AE, Blunn GW, Green J, Coathup MJ. Prevention of strain-induced osteopenia in aseptic loosening of hip prostheses using perioperative bisphosphonate. J Orthop Res. 2008;26:693–703.PubMedCrossRef Goodship AE, Blunn GW, Green J, Coathup MJ. Prevention of strain-induced osteopenia in aseptic loosening of hip prostheses using perioperative bisphosphonate. J Orthop Res. 2008;26:693–703.PubMedCrossRef
11.
Zurück zum Zitat Hilding M, Aspenberg P. Local preoperative treatment with a bisphosphonate improves the fixation of total knee prostheses. Acta Orthop. 2007;78:795–799.PubMedCrossRef Hilding M, Aspenberg P. Local preoperative treatment with a bisphosphonate improves the fixation of total knee prostheses. Acta Orthop. 2007;78:795–799.PubMedCrossRef
12.
Zurück zum Zitat Jakobsen T, Baas J, Kold S, Bechtold JE, Elmengaard B, Søballe K. Local bisphosphonate treatment increases fixation of hydroxyapatite-coated implants inserted with bone compaction. J Orthop Res. 2009;27:189–194.PubMedCentralPubMedCrossRef Jakobsen T, Baas J, Kold S, Bechtold JE, Elmengaard B, Søballe K. Local bisphosphonate treatment increases fixation of hydroxyapatite-coated implants inserted with bone compaction. J Orthop Res. 2009;27:189–194.PubMedCentralPubMedCrossRef
13.
Zurück zum Zitat Lindahl H. Epidemiology of periprosthetic femur fracture around a total hip arthroplasty. Injury. 2007;38:651–654.PubMedCrossRef Lindahl H. Epidemiology of periprosthetic femur fracture around a total hip arthroplasty. Injury. 2007;38:651–654.PubMedCrossRef
14.
Zurück zum Zitat Papapetrou PD. Bisphosphonate-associated adverse events. Hormones. 2009;8:96–110.PubMed Papapetrou PD. Bisphosphonate-associated adverse events. Hormones. 2009;8:96–110.PubMed
15.
Zurück zum Zitat Peter B, Gauthier O, Laib S, Bujoli B, Guicheux J, Janvier P, van Lenthe GH, Müller R, Zambelli PY, Bouler JM, Pioletti DP. Local delivery of bisphosphonate from coated orthopedic implants increases implant mechanical stability in osteoporotic rats. J Biomed Mater Res A. 2006;76:133–143.PubMedCrossRef Peter B, Gauthier O, Laib S, Bujoli B, Guicheux J, Janvier P, van Lenthe GH, Müller R, Zambelli PY, Bouler JM, Pioletti DP. Local delivery of bisphosphonate from coated orthopedic implants increases implant mechanical stability in osteoporotic rats. J Biomed Mater Res A. 2006;76:133–143.PubMedCrossRef
16.
Zurück zum Zitat Peter B, Pioletti DP, Laib S, Bujoli B, Pilet P, Janvier P, Guicheux J, Zambelli PY, Bouler JM, Gauthier O. Calcium phosphate drug delivery system: influence of local zoledronate release on bone implant osteointegration. Bone. 2005;36:52–60.PubMedCrossRef Peter B, Pioletti DP, Laib S, Bujoli B, Pilet P, Janvier P, Guicheux J, Zambelli PY, Bouler JM, Gauthier O. Calcium phosphate drug delivery system: influence of local zoledronate release on bone implant osteointegration. Bone. 2005;36:52–60.PubMedCrossRef
17.
Zurück zum Zitat Prieto-Alhambra B, Javaid MK, Judge A, Murray D, Carr A, Cooper C, Arden NK. Association between bisphosphonate use and implant survival after primary total arthroplasty of the knee or hip: population based retrospective cohort study. BMJ. 2011;343:1–9.CrossRef Prieto-Alhambra B, Javaid MK, Judge A, Murray D, Carr A, Cooper C, Arden NK. Association between bisphosphonate use and implant survival after primary total arthroplasty of the knee or hip: population based retrospective cohort study. BMJ. 2011;343:1–9.CrossRef
18.
Zurück zum Zitat Tanzer M, Karabasz D, Krygier JJ, Cohen R, Bobyn JD. Bone augmentation around and within porous implants by local bisphosphonate elution. Clin Orthop Relat Res. 2005;441:30–39.PubMedCrossRef Tanzer M, Karabasz D, Krygier JJ, Cohen R, Bobyn JD. Bone augmentation around and within porous implants by local bisphosphonate elution. Clin Orthop Relat Res. 2005;441:30–39.PubMedCrossRef
19.
Zurück zum Zitat Tengvall P, Skoglund B, Askendal A, Aspenberg P. Surface immobilized bisphosphonate improves stainless-steel screw fixation in rats. Biomaterials. 2004;25:2133–2138.PubMedCrossRef Tengvall P, Skoglund B, Askendal A, Aspenberg P. Surface immobilized bisphosphonate improves stainless-steel screw fixation in rats. Biomaterials. 2004;25:2133–2138.PubMedCrossRef
20.
Zurück zum Zitat Yoshinari M, Oda Y, Inoue T, Matsuzaka K, Shimono M. Bone response to calcium phosphate-coated and bisphosphonate-immobilized titanium implants. Biomaterials. 2002;23:2879–2885.PubMedCrossRef Yoshinari M, Oda Y, Inoue T, Matsuzaka K, Shimono M. Bone response to calcium phosphate-coated and bisphosphonate-immobilized titanium implants. Biomaterials. 2002;23:2879–2885.PubMedCrossRef
Metadaten
Titel
Local Alendronic Acid Elution Increases Net Periimplant Bone Formation: A Micro-CT Analysis
verfasst von
J. Dennis Bobyn, PhD
Rebecca Thompson, MEng
Letitia Lim, MD
Jenny Ann Pura, BSc
Kristian Bobyn, BA
Michael Tanzer, MD
Publikationsdatum
01.02.2014
Verlag
Springer US
Erschienen in
Clinical Orthopaedics and Related Research® / Ausgabe 2/2014
Print ISSN: 0009-921X
Elektronische ISSN: 1528-1132
DOI
https://doi.org/10.1007/s11999-013-3120-6

Weitere Artikel der Ausgabe 2/2014

Clinical Orthopaedics and Related Research® 2/2014 Zur Ausgabe

Arthropedia

Grundlagenwissen der Arthroskopie und Gelenkchirurgie. Erweitert durch Fallbeispiele, Videos und Abbildungen. 
» Jetzt entdecken

Update Orthopädie und Unfallchirurgie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.