Compromised osseous healing of dental extraction sites in zoledronic acid-treated dogs.
The goal of this study was to document how treatment with high doses of zoledronic acid affects dental extraction healing. Our results, showing significantly compromised osseous healing within the socket as well as presence of exposed bone and development of a sequestrum in one animal, provide a building block toward understanding osteonecrosis of the jaw.


OBJECTIVE
The goal of this study was to document how treatment with a bisphosphonate affects the bone tissue following dental extraction.


METHODS
Skeletally mature female beagle dogs were either untreated controls (CON) or treated with intravenous zoledronic acid (ZOL). Following the extraction of the fourth premolars, healing was allowed for 4 or 8 weeks. Properties of the extraction site were assessed using microcomputed tomography (micro-CT) and dynamic histomorphometry.


RESULTS
The initial infilling of the extraction socket with bone was not affected by ZOL, but subsequent removal of this bone was significantly suppressed compared to CON. After 8 weeks of healing, the alveolar cortical bone adjacent to the extraction socket had a remodeling rate of ∼50% per year in CON animals while ZOL-treated animals had a rate of <1% per year. One ZOL-treated animal developed exposed bone post-extraction which eventually led to the formation of a sequestrum. Assessment of the sequestrum with micro-CT and histology showed that it had features consistent with those reported in humans with osteonecrosis of the jaw.


CONCLUSIONS
These results, showing significantly compromised post-extraction osseous healing as well as presence of exposed bone and development of a sequestrum in one ZOL animal, provide a building block toward understanding the pathophysiology of osteonecrosis of the jaw.
Allen
M R
MR
Department of Anatomy and Cell Biology, 635 Barnhill Drive, MS-5035, Indianapolis, IN 46202, USA. matallen@iupui.edu
Kubek
D J
DJ
Burr
D B
DB
Ruggiero
S L
SL
Chu
T-M G
TM
D000818:Animals; D050071:Bone Density Conservation Agents / Q000009:adverse effects*; D016022:Case-Control Studies; D004164:Diphosphonates / Q000009:adverse effects*; D004285:Dogs; D005260:Female; D007093:Imidazoles / Q000009:adverse effects*; D007571:Jaw Diseases / Q000139:chemically induced* / Q000000981:diagnostic imaging; D010020:Osteonecrosis / Q000139:chemically induced* / Q000000981:diagnostic imaging; D014057:Tomography, X-Ray Computed; D014081:Tooth Extraction; D016896:Treatment Outcome; D014945:Wound Healing / Q000187:drug effects; D000077211:Zoledronic Acid
D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D007093:Imidazoles; D000077211:Zoledronic Acid
Crit Rev Oral Biol Med. 1999;10(3):384-404
10759415
J Bone Miner Res. 2008 Jun;23(6):826-36
18558816
J Clin Periodontol. 2003 Sep;30(9):809-18
12956657
J Clin Oncol. 2009 Nov 10;27(32):5356-62
19805682
J Oral Maxillofac Surg. 2005 Nov;63(11):1567-75
16243172
Br J Haematol. 2006 Sep;134(6):620-3
16889620
J Periodontal Res. 1981 Jul;16(4):441-55
6459441
Bone. 2002 Jan;30(1):2-4
11792556
J Oral Maxillofac Surg. 2007 Mar;65(3):415-23
17307586
J Am Dent Assoc. 2005 Dec;136(12):1658-68
16383047
J Am Dent Assoc. 1960 Jul;61:32-44
13793201
J Oral Maxillofac Surg. 2004 May;62(5):527-34
15122554
Bone. 2008 Oct;43(4):653-62
18582604
J Clin Oncol. 2006 Oct 20;24(30):4895-900
17001071
J Oral Pathol Med. 2010 May;39(5):390-6
20202091
J Oral Maxillofac Surg. 2008 May;66(5):987-94
18423290
J Bone Miner Metab. 2009;27(6):663-72
19436946
Oncologist. 2008 Aug;13(8):911-20
18695259
J Bone Miner Res. 2007 Oct;22(10):1479-91
17663640
J Bone Miner Res. 2010 Jul;25(7):1668-79
20200952
Virchows Arch. 2007 Dec;451(6):1009-17
17952459
Int J Oral Maxillofac Surg. 2004 Apr;33(3):286-93
15287313
J Bone Miner Res. 1987 Dec;2(6):595-610
3455637
Mayo Clin Proc. 2006 Aug;81(8):1047-53
16901028
Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2006 Oct;102(4):433-41
16997108
J Oral Maxillofac Surg. 2009 May;67(5 Suppl):61-70
19371816
Annu Rev Med. 2009;60:85-96
18928335
J Bone Miner Res. 1999 Jun;14(6):969-79
10352106
J Dent Res. 2007 Nov;86(11):1013-21
17959890
Oral Oncol. 2009 Feb;45(2):164-72
18715819
J Dent Res. 1966 Jan-Feb;45(1):213
4955384
J Bone Miner Res. 1990 Oct;5(10):1063-7
2080717
J Bone Miner Res. 2010 Jan;25(1):98-105
19580463
Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2010 Mar;109(3):385-91
20060339
N Engl J Med. 2006 May 25;354(21):2250-61
16723616
J Bone Miner Metab. 2010 Mar;28(2):165-75
19882100
J Bone Miner Res. 2010 Jun;25(6):1337-49
20200938
Ann Intern Med. 2006 May 16;144(10):753-61
16702591