A histomorphometric study of the effect of doxycycline and erythromycin on bone formation in dental alveolar socket of rat

Authors

1 Department of Periodontology, Torabinejad Dental Research Center, School of Dentistry, Isfahan University of Medical Sciences, Isfahan, Iran

2 Department of Oral and Maxillofacial Pathology, Torabinejad Dental Research Center, School of Dentistry, Isfahan University of Medical Sciences, Isfahan, Iran

3 Department of Pharmacology, School of Pharmacy, Isfahan University of Medical Sciences, Isfahan, Iran

4 Department of Oral and Maxillofacial Medicine, School of Dentistry, Isfahan University of Medical Sciences, Isfahan, Iran

5 Department of Oral and Maxillofacial Medicine, School of Dentistry, Qom University of Medical Sciences, Qom, Iran

Abstract

Background: The aim of the present study was to evaluate whether subantimicrobial doses of doxycycline (DOX) and erythromycin (EM) used for the treatment of peri-implant osteolysis due to their anti-osteoclastogenesis can interfere with the osseous wound healing process in rat alveolar socket.
Materials and Methods: Forty-five male Wistar rats had their first maxillary right molar extracted and were divided into three groups. DOX and EM at the doses of 5 mg/kg/day orally (p.o.) and 2 mg/kg/day intraperitoneally (i.p.) were administered respectively to two separate groups for 7 days after operation. In the control group the animals received normal saline (5 ml/kg). Five rats were sacrificed at 7, 14 and 21 days post-extraction in each study group. A histomorphometric analysis was used to evaluate new bone formation inside the alveolar socket. Significant level was set at 0.05.
Results: The findings showed that the percentage of new bone formation (NBF) enhanced significantly on days 7 and 14. There was no significant difference in the NBF between DOX and EM groups.
Conclusion: Short-term treatment with both DOX and EM enhanced new bone formation without any advances in favor of each drug.

Keywords

1.
Amler MH, Johnson PL, Salman I. Histological and histochemical investigation of human alveolar socket healing in undisturbed extraction wounds. J Am Dent Assoc 1960;61:32-44.  Back to cited text no. 1
    
2.
Devlin H, Sloan P. Early bone healing events in the human extraction socket. Int J Oral Maxillofac Surg 2002;31:641-5.  Back to cited text no. 2
    
3.
Bassetti C, Kallenberger A. Influence of chlorhexidine rinsing on the healing of oral mucosa and osseous lesions. J Clin Periodontol 1980;7:443-56.  Back to cited text no. 3
    
4.
Manolagas SC. Birth and death of bone cells: Basic regulatory mechanisms and implications for the pathogenesis and treatment of osteoporosis. Endocr Rev 2000;21:115-37.  Back to cited text no. 4
    
5.
Liu C, Wu Z, Sun HC. The effect of simvastatin on mRNA expression of transforming growth factor-beta1, bone morphogenetic protein-2 and vascular endothelial growth factor in tooth extraction socket. Int J Oral Sci 2009;1:90-8.  Back to cited text no. 5
    
6.
Agnihotri R, Gaur S. Chemically modified tetracyclines: Novel therapeutic agents in the management of chronic periodontitis. Indian J Pharmacol 2012;44:161-7.  Back to cited text no. 6
[PUBMED]  Medknow Journal  
7.
Holmes SG, Still K, Buttle DJ, Bishop NJ, Grabowski PS. Chemically modified tetracyclines act through multiple mechanisms directly on osteoclast precursors. Bone 2004;35:471-8.  Back to cited text no. 7
    
8.
Williams S, Wakisaka A, Zeng QQ, Barnes J, Martin G, Wechter WJ, et al. Minocycline prevents the decrease in bone mineral density and trabecular bone in ovariectomized aged rats. Bone 1996;19:637-44.  Back to cited text no. 8
    
9.
Golub LM, Ramamurthy NS, Kaneko H, Sasaki T, Rifkin B, McNamara TF. Tetracycline administration prevents diabetes-induced osteopenia in the rat: Initial observations. Res Commun Chem Pathol Pharmacol 1990;68:27-40.  Back to cited text no. 9
    
10.
Bain S, Ramamurthy NS, Impeduglia T, Scolman S, Golub LM, Rubin C. Tetracycline prevents cancellous bone loss and maintains near-normal rates of bone formation in streptozotocin diabetic rats. Bone 1997;21:147-53.  Back to cited text no. 10
    
11.
Aoyagi M, Sasaki T, Ramamurthy NS, Golub LM. Tetracycline/flurbiprofen combination therapy modulates bone remodeling in ovariectomized rats: Preliminary observations. Bone 1996;19:629-35.  Back to cited text no. 11
    
12.
Sasaki T, Ramamurthy N, Golub LM. Long-term therapy with a new chemically modified tetracycline (CMT-8) inhibits bone loss in femurs of ovariectomized rats. Adv Dent Res 1998;12:76-81.  Back to cited text no. 12
    
13.
Bettany JT, Peet NM, Wolowacz RG, Skerry TM, Grabowski PS. Tetracyclines induce apoptosis in osteoclasts. Bone 2000;27:75-80.  Back to cited text no. 13
    
14.
Shinkai M, Henke MO, Rubin BK. Macrolide antibiotics as immunomodulatory medications: Proposed mechanisms of action. Pharmacol Ther 2008;117:393-405.  Back to cited text no. 14
    
15.
Giamarellos-Bourboulis EJ. Macrolides beyond the conventional antimicrobials: A class of potent immunomodulators. Int J Antimicrob Agents 2008;31:12-20.  Back to cited text no. 15
    
16.
Cervin A. The anti-inflammatory effect of erythromycin and its derivatives, with special reference to nasal polyposis and chronic sinusitis. Acta Otolaryngol 2001;121:83-92.  Back to cited text no. 16
    
17.
Ren W, Li XH, Chen BD, Wooley PH. Erythromycin inhibits wear debris-induced osteoclastogenesis by modulation of murine macrophage NF-kappaB activity. J Orthop Res 2004;22:21-9.  Back to cited text no. 17
    
18.
Ren W, Zhang R, Hawkins M, Shi T, Markel DC. Efficacy of periprosthetic erythromycin delivery for wear debris-induced inflammation and osteolysis. Inflamm Res 2010;59:1091-7.  Back to cited text no. 18
    
19.
Buduneli E, Vardar S, Buduneli N, Berdeli AH, Türkoðlu O, Baºkesen A, et al. Effects of combined systemic administration of low-dose doxycycline and alendronate on endotoxin-induced periodontitis in rats. J Periodontol 2004;75:1516-23.  Back to cited text no. 19
    
20.
Joos AA. Pharmacologic interactions of antibiotics and psychotropic drugs. Psychiatr Prax 1998;25:57-60.  Back to cited text no. 20
    
21.
Carvalho TL, Bombonato KF, Brentegani LG. Histometric analysis of rat alveolar wound healing. Braz Dent J 1997;8:9-12.  Back to cited text no. 21
    
22.
Elsubeihi ES, Heersche JN. Quantitative assessment of post-extraction healing and alveolar ridge remodelling of the mandible in female rats. Arch Oral Biol 2004;49:401-12.  Back to cited text no. 22
    
23.
Iizuka T, Miller SC, Marks SC Jr. Alveolar bone remodeling after tooth extraction in normal and osteopetrotic (ia) rats. J Oral Pathol Med 1992;21:150-5.  Back to cited text no. 23
    
24.
Soory M. A role for non-antimicrobial actions of tetracyclines in combating oxidative stress in periodontal and metabolic diseases: A literature review. Open Dent J 2008;2:5-12.  Back to cited text no. 24
    
25.
Lee L, Liu J, Manuel J, Gorczynski RM. A role for the immunomodulatory molecules CD200 and CD200R in regulating bone formation. Immunol Lett 2006;105:150-8.  Back to cited text no. 25
    
26.
Gomes PS, Fernandes MH. Effect of therapeutic levels of doxycycline and minocycline in the proliferation and differentiation of human bone marrow osteoblastic cells. Arch Oral Biol 2007;52:251-9.  Back to cited text no. 26
    
27.
Ferraz MP, Mateus AY, Sousa JC, Monteiro FJ. Nanohydroxyapatite microspheres as delivery system for antibiotics: Release kinetics, antimicrobial activity, and interaction with osteoblasts. J Biomed Mater Res A 2007;81:994-1004.  Back to cited text no. 27
    
28.
Alkan A, Erdem E, Günhan O, Karasu C. Histomorphometric evaluation of the effect of doxycycline on the healing of bone defects in experimental diabetes mellitus: A pilot study. J Oral Maxillofac Surg 2002;60:898-904.  Back to cited text no. 28
    
29.
Olmarker K. Reduction of adhesion formation and promotion of wound healing after laminectomy by pharmacological inhibition of pro-inflammatory cytokines: An experimental study in the rat. Eur Spine J 2010;19:2117-21.  Back to cited text no. 29
    
30.
Cummings GR, Torabinejad M. Effect of systemic doxycycline on alveolar bone loss after periradicular surgery. J Endod 2000;26:325-7.  Back to cited text no. 30
    
31.
Mavragani M, Brudvik P, Selvig KA. Orthodontically induced root and alveolar bone resorption: Inhibitory effect of systemic doxycycline administration in rats. Eur J Orthod 2005;27:215-25.  Back to cited text no. 31
    
32.
Lamano-Carvalho TL. Effect of conventional and COX-2 selective non-steroidal anti-inflammatory drugs on bone healing. Acta Ortop Bras 2007;15:166-8.  Back to cited text no. 32
    
33.
Sugarman BJ, Lewis GD, Eessalu TE, Aggarwal BB, Shepard HM. Effects of growth factors on the antiproliferative activity of tumor necrosis factors. Cancer Res 1987;47:780-6.  Back to cited text no. 33
    
34.
Waetzig GH, Rosenstiel P, Arlt A, Till A, Bräutigam K, Schäfer H, et al. Soluble tumor necrosis factor (TNF) receptor-1 induces apoptosis via reverse TNF signaling and autocrine transforming growth factor-beta1. FASEB J 2005;19:91-3.  Back to cited text no. 34