Skip to main content
Erschienen in: Clinical Orthopaedics and Related Research® 2/2011

01.02.2011 | Symposium: Papers Presented at the Hip Society Meetings 2010

Bisphosphonate Remains Highly Localized After Elution From Porous Implants

verfasst von: Kimberly McKenzie, MEng, J. Dennis Bobyn, PhD, Jacintha Roberts, MEng, Dorota Karabasz, BSc, Michael Tanzer, MD

Erschienen in: Clinical Orthopaedics and Related Research® | Ausgabe 2/2011

Einloggen, um Zugang zu erhalten

Abstract

Background

Local elution of zoledronic acid from a porous implant reportedly enhances periimplant bone formation and implant fixation. However, there is no information in the literature on the extent to which eluted bisphosphonate remains localized around the implant or becomes systemically distributed.

Questions/purposes

We ascertained to what extent eluted zoledronic acid remains local and whether there is systemic exposure after local elution from porous implants.

Methods

A hydroxyapatite-coated porous tantalum implant dosed with 100 μg 14C-labeled zoledronic acid was implanted into the left femoral intramedullary canal of six dogs. Bone samples near to and distant from the implant were harvested from three dogs at 6 weeks and three dogs at 52 weeks. The concentration of radiolabeled bisphosphonate in each sample was quantified using liquid scintillation spectrophotometry and its distribution in periimplant bone was revealed by exposing histologic sections to autoradiography film.

Results

In all six dogs, the concentration of zoledronic acid in immediate periimplant bone was two orders of magnitude higher than in any other sampled tissue, averaging 732.6 ng/g at 6 weeks and 377.2 ng/g at 52 weeks. Minute amounts of zoledronic acid (≤ 7.2 ng/g) were detected throughout the skeleton, indicating some escape into the circulation after local elution. Autoradiographs revealed the greatest concentration of zoledronic acid on and within the implant, with rapid decrease short distances away and no uptake within the femoral cortex.

Conclusions

Zoledronic acid eluted from an implant remains mainly localized with minimal systemic distribution.

Clinical Relevance

Local bisphosphonate elution reduces the risk of systemic side effects and skeletal bisphosphonate exposure.
Literatur
1.
Zurück zum Zitat Allen MR, Iwata K, Phipps R, Burr DB. Alterations in canine vertebral bone turnover, microdamage accumulation, and biomechanical properties following 1-year treatment with clinical treatment doses of risedronate or alendronate. Bone. 2006;39:872–879.CrossRefPubMed Allen MR, Iwata K, Phipps R, Burr DB. Alterations in canine vertebral bone turnover, microdamage accumulation, and biomechanical properties following 1-year treatment with clinical treatment doses of risedronate or alendronate. Bone. 2006;39:872–879.CrossRefPubMed
2.
Zurück zum Zitat Amanat N, McDonald M, Godfrey C, Bilston L, Little D. Optimal timing of a single dose of zoledronic acid to increase strength in rat fracture repair. J Bone Miner Res. 2007;22:867–876.CrossRefPubMed Amanat N, McDonald M, Godfrey C, Bilston L, Little D. Optimal timing of a single dose of zoledronic acid to increase strength in rat fracture repair. J Bone Miner Res. 2007;22:867–876.CrossRefPubMed
3.
Zurück zum Zitat Åstrand J, Aspenberg P. Topical, single dose bisphosphonate treatment reduced bone resorption in a rat model for prosthetic loosening. J Orthop Res. 2004;22:244–249.CrossRefPubMed Åstrand J, Aspenberg P. Topical, single dose bisphosphonate treatment reduced bone resorption in a rat model for prosthetic loosening. J Orthop Res. 2004;22:244–249.CrossRefPubMed
4.
Zurück zum Zitat Black DM, Delmas PD, Eastell R, Reid IR, Boonen S, Cauley JA, Cosman F, Lakatos P, Leung PC, Man Z, Mautalen C, Mesenbrink P, Hu H, Caminis J, Tong K, Rosario-Jansen T, Krasnow J, Hue TF, Sellmeyer D, Eriksen EF, Cummings SR. Once-yearly zoledronic acid for treatment of postmenopausal osteoporosis. N Engl J Med. 2007;356:1809–1822.CrossRefPubMed Black DM, Delmas PD, Eastell R, Reid IR, Boonen S, Cauley JA, Cosman F, Lakatos P, Leung PC, Man Z, Mautalen C, Mesenbrink P, Hu H, Caminis J, Tong K, Rosario-Jansen T, Krasnow J, Hue TF, Sellmeyer D, Eriksen EF, Cummings SR. Once-yearly zoledronic acid for treatment of postmenopausal osteoporosis. N Engl J Med. 2007;356:1809–1822.CrossRefPubMed
5.
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 Am. 2009;91:23–31.CrossRefPubMed 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 Am. 2009;91:23–31.CrossRefPubMed
6.
Zurück zum Zitat Drake MT, Clarke BT, Khosla S. Bisphosphonates: mechanisms of action and role in clinical Practice. Mayo Clin Proc. 2008;83:1032–1045.CrossRefPubMed Drake MT, Clarke BT, Khosla S. Bisphosphonates: mechanisms of action and role in clinical Practice. Mayo Clin Proc. 2008;83:1032–1045.CrossRefPubMed
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.CrossRefPubMed 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.CrossRefPubMed
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.CrossRefPubMed 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.CrossRefPubMed
9.
Zurück zum Zitat Goh SK, Yang KY, Koh JS, Wong MK, Chua SY, Chua DT, Howe TS. Subtrochanteric insufficiency fractures in patients on alendronate therapy: a caution. J Bone Joint Surg Br. 2007;89:349–353.CrossRefPubMed Goh SK, Yang KY, Koh JS, Wong MK, Chua SY, Chua DT, Howe TS. Subtrochanteric insufficiency fractures in patients on alendronate therapy: a caution. J Bone Joint Surg Br. 2007;89:349–353.CrossRefPubMed
10.
Zurück zum Zitat Hilding M, Aspenberg P. Local peroperative treatment with a bisphosphonate improves the fixation of total knee prostheses. A randomized, double-blind radiostereometric study of 50 patients. Acta Orthop. 2007;78:795–799.CrossRefPubMed Hilding M, Aspenberg P. Local peroperative treatment with a bisphosphonate improves the fixation of total knee prostheses. A randomized, double-blind radiostereometric study of 50 patients. Acta Orthop. 2007;78:795–799.CrossRefPubMed
11.
Zurück zum Zitat Hilding M, Ryd L, Toksvig-Larsen S, Aspenberg P. Clodronate prevents prosthetic migration: a randomized radiostereometric study of 50 total knee patients. Acta Orthop Scand. 2000;71:553–557.CrossRefPubMed Hilding M, Ryd L, Toksvig-Larsen S, Aspenberg P. Clodronate prevents prosthetic migration: a randomized radiostereometric study of 50 total knee patients. Acta Orthop Scand. 2000;71:553–557.CrossRefPubMed
12.
Zurück zum Zitat Jakobsen T, Baas J, Kold S, Bechtold JE, Elmengaard B, Soballe K. Local bisphosphonate treatment increases fixation of hydroxyapatite-coated implants inserted with bone compaction. J Orthop Res. 2009;27:189–194.CrossRefPubMed Jakobsen T, Baas J, Kold S, Bechtold JE, Elmengaard B, Soballe K. Local bisphosphonate treatment increases fixation of hydroxyapatite-coated implants inserted with bone compaction. J Orthop Res. 2009;27:189–194.CrossRefPubMed
13.
Zurück zum Zitat Kwek EB, Koh JS, Howe TS. More on atypical fractures of the femoral diaphysis [Letter]. N Engl J Med. 2008;359:316–318.CrossRefPubMed Kwek EB, Koh JS, Howe TS. More on atypical fractures of the femoral diaphysis [Letter]. N Engl J Med. 2008;359:316–318.CrossRefPubMed
14.
Zurück zum Zitat Legay F, Gauron S, Deckert F, Gosset G, Pfaar U, Ravera C, Wiegand H, Schran H. Development and validation of a highly sensitive RIA for zoledronic acid, a new potent heterocyclic bisphosphonate in human serum, plasma and urine. J Pharm Biomed Anal. 2002;30:897–911.CrossRefPubMed Legay F, Gauron S, Deckert F, Gosset G, Pfaar U, Ravera C, Wiegand H, Schran H. Development and validation of a highly sensitive RIA for zoledronic acid, a new potent heterocyclic bisphosphonate in human serum, plasma and urine. J Pharm Biomed Anal. 2002;30:897–911.CrossRefPubMed
15.
Zurück zum Zitat Lenart BA, Lorich DG, Lane JM. Atypicial fractures of the femoral diaphysis in postmenopausal women taking alendronate. N Engl J Med. 2008;358:1304–1306.CrossRefPubMed Lenart BA, Lorich DG, Lane JM. Atypicial fractures of the femoral diaphysis in postmenopausal women taking alendronate. N Engl J Med. 2008;358:1304–1306.CrossRefPubMed
16.
Zurück zum Zitat Lyles KW, Colón-Emeric CS, Magaziner JS, Adachi JD, Pieper CF, Mautalen C, Hyldstrup L, Recknor C, Nordsletten L, Moore KA, Lavecchia C, Zhang J, Mesenbrink P, Hodgson PK, Abrams K, Orloff JJ, Horowitz Z, Eriksen EF, Boonen S. Zoledronic acid and clinical fractures and mortality after hip fracture. N Engl J Med. 2007:357:1799–1809.CrossRefPubMed Lyles KW, Colón-Emeric CS, Magaziner JS, Adachi JD, Pieper CF, Mautalen C, Hyldstrup L, Recknor C, Nordsletten L, Moore KA, Lavecchia C, Zhang J, Mesenbrink P, Hodgson PK, Abrams K, Orloff JJ, Horowitz Z, Eriksen EF, Boonen S. Zoledronic acid and clinical fractures and mortality after hip fracture. N Engl J Med. 2007:357:1799–1809.CrossRefPubMed
17.
Zurück zum Zitat Mashiba T, Hirano T, Turner CH, Forwood MR, Johnston CC, Burr DB. Suppressed bone turnover by bisphosphonates increases microdamage accumulation and reduces some biomechanical properties in dog rib. J Bone Miner Res. 2000;15:613–620.CrossRefPubMed Mashiba T, Hirano T, Turner CH, Forwood MR, Johnston CC, Burr DB. Suppressed bone turnover by bisphosphonates increases microdamage accumulation and reduces some biomechanical properties in dog rib. J Bone Miner Res. 2000;15:613–620.CrossRefPubMed
18.
Zurück zum Zitat Mashiba T, Turner CH, Hirano T, Forwood MR, Johnston CC, Burr DB. Effects of suppressed bone turnover by bisphosphonates on microdamage accumulation and biomechanical properties in clinically relevant skeletal sites in beagles. Bone. 2001;28:524–531.CrossRefPubMed Mashiba T, Turner CH, Hirano T, Forwood MR, Johnston CC, Burr DB. Effects of suppressed bone turnover by bisphosphonates on microdamage accumulation and biomechanical properties in clinically relevant skeletal sites in beagles. Bone. 2001;28:524–531.CrossRefPubMed
19.
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
20.
Zurück zum Zitat Peter B, Gauthier O, Laïb 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 implants mechanical stability in osteoporotic rats. J Biomed Mat Res Part A. 2006;76:133–143.CrossRef Peter B, Gauthier O, Laïb 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 implants mechanical stability in osteoporotic rats. J Biomed Mat Res Part A. 2006;76:133–143.CrossRef
21.
Zurück zum Zitat Peter B, Pioletti DP, Laïb 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.CrossRefPubMed Peter B, Pioletti DP, Laïb 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.CrossRefPubMed
22.
Zurück zum Zitat Russell RG, Xia Z, Dunford JE, Oppermann U, Kwaasi A, Hulley PA, Kavanagh KL, Triffitt JT, Lundy MW, Phipps RJ, Barnett BL, Coxon FP, Rogers MJ, Watts NB, Ebetino FH. Bisphosphonates: an update on mechanisms of action and how these relate to clinical efficacy. Ann NY Acad Sci. 2007;1117:209–257.CrossRefPubMed Russell RG, Xia Z, Dunford JE, Oppermann U, Kwaasi A, Hulley PA, Kavanagh KL, Triffitt JT, Lundy MW, Phipps RJ, Barnett BL, Coxon FP, Rogers MJ, Watts NB, Ebetino FH. Bisphosphonates: an update on mechanisms of action and how these relate to clinical efficacy. Ann NY Acad Sci. 2007;1117:209–257.CrossRefPubMed
23.
Zurück zum Zitat Saleh KJ, Mulhall KJ, Hofmann AA, Bolognesi MP, Laskin RS. Primary total knee arthroplasty outcomes. In: Barrack RL, Booth RE Jr, Lonner JH, McCarthy JC, Mont MA, Rubash HE, eds. Orthopaedic Knowledge Update 3 - Hip and Knee Reconstruction. Rosemont, IL: Amer Acad Orthop Surg; 2006:93–110. Saleh KJ, Mulhall KJ, Hofmann AA, Bolognesi MP, Laskin RS. Primary total knee arthroplasty outcomes. In: Barrack RL, Booth RE Jr, Lonner JH, McCarthy JC, Mont MA, Rubash HE, eds. Orthopaedic Knowledge Update 3 - Hip and Knee Reconstruction. Rosemont, IL: Amer Acad Orthop Surg; 2006:93–110.
24.
Zurück zum Zitat Sporer S, Paprosky WG, Berry DJ. Hip revision. In: Barrack RL, Booth RE Jr, Lonner JH, McCarthy JC, Mont MA, Rubash HE, eds. Orthopaedic Knowledge Update 3 - Hip and Knee Reconstruction. Rosemont, IL: Amer Acad Orthop Surg; 2006:457–474. Sporer S, Paprosky WG, Berry DJ. Hip revision. In: Barrack RL, Booth RE Jr, Lonner JH, McCarthy JC, Mont MA, Rubash HE, eds. Orthopaedic Knowledge Update 3 - Hip and Knee Reconstruction. Rosemont, IL: Amer Acad Orthop Surg; 2006:457–474.
25.
Zurück zum Zitat Stadelmann VA, Gauthier O, Terrier A, Bouler JM, Pioletti DP. Implants delivering bisphosphonate locally increase periprosthetic bone density in an osteoporotic sheep model: a pilot study. Eur Cell Mater. 2008;16:10–16.PubMed Stadelmann VA, Gauthier O, Terrier A, Bouler JM, Pioletti DP. Implants delivering bisphosphonate locally increase periprosthetic bone density in an osteoporotic sheep model: a pilot study. Eur Cell Mater. 2008;16:10–16.PubMed
26.
Zurück zum Zitat Suratwala SJ, Cho SK, van Raalte JJ, Park SH, Seo SW, Chang SS, Gardner TR, Lee FY. Enhancement of periprosthetic bone qwuality with topical hydroxyapatite-bisphosphonate composite. J Bone Joint Surg Am. 2008;90:2189–2196.CrossRefPubMed Suratwala SJ, Cho SK, van Raalte JJ, Park SH, Seo SW, Chang SS, Gardner TR, Lee FY. Enhancement of periprosthetic bone qwuality with topical hydroxyapatite-bisphosphonate composite. J Bone Joint Surg Am. 2008;90:2189–2196.CrossRefPubMed
27.
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.CrossRefPubMed 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.CrossRefPubMed
28.
Zurück zum Zitat Yaffe A, Binderman I, Breuer E, Pinto T, Golomb G. Disposition of alendronate following local delivery in a rat jaw. J Periodontol. 1999;70:893–895.CrossRefPubMed Yaffe A, Binderman I, Breuer E, Pinto T, Golomb G. Disposition of alendronate following local delivery in a rat jaw. J Periodontol. 1999;70:893–895.CrossRefPubMed
Metadaten
Titel
Bisphosphonate Remains Highly Localized After Elution From Porous Implants
verfasst von
Kimberly McKenzie, MEng
J. Dennis Bobyn, PhD
Jacintha Roberts, MEng
Dorota Karabasz, BSc
Michael Tanzer, MD
Publikationsdatum
01.02.2011
Verlag
Springer-Verlag
Erschienen in
Clinical Orthopaedics and Related Research® / Ausgabe 2/2011
Print ISSN: 0009-921X
Elektronische ISSN: 1528-1132
DOI
https://doi.org/10.1007/s11999-010-1527-x

Weitere Artikel der Ausgabe 2/2011

Clinical Orthopaedics and Related Research® 2/2011 Zur Ausgabe

Symposium: Papers Presented at the Hip Society Meetings 2010

Hard-on-Hard Total Hip Impingement Causes Extreme Contact Stress Concentrations

Symposium: Papers Presented at the Hip Society Meetings 2010

Ceramic-on-Ceramic Total Hip Arthroplasty: Incidence of Instability and Noise

Symposium: Papers Presented at the Hip Society Meetings 2010

A Monoblock Porous Tantalum Acetabular Cup Has No Osteolysis on CT at 10 Years

Arthropedia

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

Notfall-TEP der Hüfte ist auch bei 90-Jährigen machbar

26.04.2024 Hüft-TEP Nachrichten

Ob bei einer Notfalloperation nach Schenkelhalsfraktur eine Hemiarthroplastik oder eine totale Endoprothese (TEP) eingebaut wird, sollte nicht allein vom Alter der Patientinnen und Patienten abhängen. Auch über 90-Jährige können von der TEP profitieren.

Arthroskopie kann Knieprothese nicht hinauszögern

25.04.2024 Gonarthrose Nachrichten

Ein arthroskopischer Eingriff bei Kniearthrose macht im Hinblick darauf, ob und wann ein Gelenkersatz fällig wird, offenbar keinen Unterschied.

Therapiestart mit Blutdrucksenkern erhöht Frakturrisiko

25.04.2024 Hypertonie Nachrichten

Beginnen ältere Männer im Pflegeheim eine Antihypertensiva-Therapie, dann ist die Frakturrate in den folgenden 30 Tagen mehr als verdoppelt. Besonders häufig stürzen Demenzkranke und Männer, die erstmals Blutdrucksenker nehmen. Dafür spricht eine Analyse unter US-Veteranen.

Ärztliche Empathie hilft gegen Rückenschmerzen

23.04.2024 Leitsymptom Rückenschmerzen Nachrichten

Personen mit chronischen Rückenschmerzen, die von einfühlsamen Ärzten und Ärztinnen betreut werden, berichten über weniger Beschwerden und eine bessere Lebensqualität.

Update Orthopädie und Unfallchirurgie

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