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Adjuvant therapy with 1% alendronate gel for experimental periodontitis treatment in rats

  • de Campos Kajimoto, Natalia (Department of Periodontics, The University of Texas Health Science Center at San Antonio) ;
  • de Paiva Buischi, Yvonne (Department of Periodontics, The University of Texas Health Science Center at San Antonio) ;
  • Loomer, Peter Michael (Department of Periodontics, The University of Texas Health Science Center at San Antonio) ;
  • Bromage, Timothy G. (Department of Biomaterials & Biomimetics, New York University College of Dentistry) ;
  • Ervolino, Edilson (Division of Histology, Department of Basic Sciences, Sao Paulo State University (UNESP), School of Dentistry) ;
  • Fucini, Stephen Enrico ;
  • Pola, Natalia Marcumini (Division of Periodontics, Department of Semiology and Clinic, Federal University of Pelotas (UFPEL), School of Dentistry) ;
  • Pirovani, Beatriz Ommati (Division of Periodontology, Department of Surgery and Integrated Clinic, Sao Paulo State University (UNESP), School of Dentistry) ;
  • Morabito, Maria Juliana Sismeiro (Division of Periodontology, Department of Surgery and Integrated Clinic, Sao Paulo State University (UNESP), School of Dentistry) ;
  • de Almeida, Juliano Milanezi (Division of Periodontology, Department of Surgery and Integrated Clinic, Sao Paulo State University (UNESP), School of Dentistry) ;
  • Furlaneto, Flavia Aparecida Chaves (Division of Periodontology, Departament of Oral Maxillofacial Surgery and Periodontology, University of Sao Paulo (USP), School of Dentistry) ;
  • Nagata, Maria Jose Hitomi (Division of Periodontology, Department of Surgery and Integrated Clinic, Sao Paulo State University (UNESP), School of Dentistry)
  • Received : 2021.02.03
  • Accepted : 2021.05.10
  • Published : 2021.12.31

Abstract

Purpose: The aim of this study was to evaluate the effects of locally delivered 1% alendronate (ALN) gel used as an adjunct to non-invasive periodontal therapy. Methods: Ligature-induced periodontitis was performed in 96 rats. The ligature was tied in the cervical area of the mandibular left first molar. The animals were randomly divided into 4 groups: 1) NT, no treatment; 2) SRP, scaling and root planning; 3) SRP/PLA, SRP followed by filling the periodontal pocket with placebo gel (PLA); and 4) SRP/ALN, SRP followed by filling the periodontal pockets with 1% ALN gel. Histomorphometric (percentage of bone in the furcation region [PBF]) and immunohistochemical (receptor activator of nuclear factor-κB ligand, osteoprotegerin, and tartrate-resistant acid phosphatase) analyses were performed. Data were statistically analyzed, with the threshold of statistical significance set at P≤0.05. Results: The SRP, SRP/PLA, and SRP/ALN groups presented a higher PBF than the NT group (P≤0.01) at 7, 15, and 30 days. The SRP/ALN group presented a higher PBF than the SRP/PLA group in all experimental periods, as well as a higher PBF than the SRP group at 15 and 30 days. No differences were observed in the immunohistochemical analyses (P>0.05 for all). Conclusions: Locally delivered 1% ALN gel used as an adjunct to SRP enhanced bone regeneration in the furcation region in a rat model of experimental periodontitis.

Keywords

Acknowledgement

Maria Juliana S. D. Morabito received a scholarship from the Sao Paulo Research Foundation (FAPESP, Sao Paulo, SP, Brazil, Grant #18/03331-1). Dr. Natalia de Campos received a scholarship from the Coordination for the Improvement of Higher Education Personnel (CAPES, Brasilia, DF, Brazil).

References

  1. Bartold PM, Van Dyke TE. Host modulation: controlling the inflammation to control the infection. Periodontol 2000 2017;75:317-29. https://doi.org/10.1111/prd.12169
  2. Jepsen K, Jepsen S. Antibiotics/antimicrobials: systemic and local administration in the therapy of mild to moderately advanced periodontitis. Periodontol 2000 2016;71:82-112. https://doi.org/10.1111/prd.12121
  3. Akram Z, Abduljabbar T, Sauro S, Daood U. Effect of photodynamic therapy and laser alone as adjunct to scaling and root planing on gingival crevicular fluid inflammatory proteins in periodontal disease: A systematic review. Photodiagnosis Photodyn Ther 2016;16:142-53. https://doi.org/10.1016/j.pdpdt.2016.09.004
  4. Lane N, Armitage GC, Loomer P, Hsieh S, Majumdar S, Wang HY, et al. Bisphosphonate therapy improves the outcome of conventional periodontal treatment: results of a 12-month, randomized, placebocontrolled study. J Periodontol 2005;76:1113-22. https://doi.org/10.1902/jop.2005.76.7.1113
  5. Pradeep AR, Kumari M, Rao NS, Naik SB. 1% alendronate gel as local drug delivery in the treatment of Class II furcation defects: a randomized controlled clinical trial. J Periodontol 2013;84:307-15. https://doi.org/10.1902/jop.2012.110729
  6. Nakagawa T, Ohta K, Kubozono K, Ishida Y, Naruse T, Takechi M, et al. Zoledronate inhibits receptor activator of nuclear factor kappa-B ligand-induced osteoclast differentiation via suppression of expression of nuclear factor of activated T-cell c1 and carbonic anhydrase 2. Arch Oral Biol 2015;60:557-65. https://doi.org/10.1016/j.archoralbio.2014.09.012
  7. Reszka AA, Rodan GA. Mechanism of action of bisphosphonates. Curr Osteoporos Rep 2003;1:45-52. https://doi.org/10.1007/s11914-003-0008-5
  8. Teronen O, Konttinen YT, Lindqvist C, Salo T, Ingman T, Lauhio A, et al. Human neutrophil collagenase MMP-8 in peri-implant sulcus fluid and its inhibition by clodronate. J Dent Res 1997;76:1529-37. https://doi.org/10.1177/00220345970760090401
  9. Giannobile WV. Host-response therapeutics for periodontal diseases. J Periodontol 2008;79:1592-600. https://doi.org/10.1902/jop.2008.080174
  10. Sharma A, Pradeep AR. Clinical efficacy of 1% alendronate gel as a local drug delivery system in the treatment of chronic periodontitis: a randomized, controlled clinical trial. J Periodontol 2012;83:11-8. https://doi.org/10.1902/jop.2011.110091
  11. Weinreb M, Quartuccio H, Seedor JG, Aufdemorte TB, Brunsvold M, Chaves E, et al. Histomorphometrical analysis of the effects of the bisphosphonate alendronate on bone loss caused by experimental periodontitis in monkeys. J Periodontal Res 1994;29:35-40. https://doi.org/10.1111/j.1600-0765.1994.tb01088.x
  12. Malden N, Lopes V. An epidemiological study of alendronate-related osteonecrosis of the jaws. A case series from the south-east of Scotland with attention given to case definition and prevalence. J Bone Miner Metab 2012;30:171-82. https://doi.org/10.1007/s00774-011-0299-z
  13. Pradeep AR, Sharma A, Rao NS, Bajaj P, Naik SB, Kumari M. Local drug delivery of alendronate gel for the treatment of patients with chronic periodontitis with diabetes mellitus: a double-masked controlled clinical trial. J Periodontol 2012a;83:1322-8. https://doi.org/10.1902/jop.2012.110292
  14. Sharma A, Raman A, Pradeep AR. Role of 1% alendronate gel as adjunct to mechanical therapy in the treatment of chronic periodontitis among smokers. J Appl Oral Sci 2017;25:243-9. https://doi.org/10.1590/1678-7757-2016-0201
  15. Dutra BC, Oliveira AM, Oliveira PA, Manzi FR, Cortelli SC, Cota LO, et al. Effect of 1% sodium alendronate in the non-surgical treatment of periodontal intraosseous defects: a 6-month clinical trial. J Appl Oral Sci 2017;25:310-7. https://doi.org/10.1590/1678-7757-2016-0252
  16. Sharma A, Pradeep AR. Clinical efficacy of 1% alendronate gel in adjunct to mechanotherapy in the treatment of aggressive periodontitis: a randomized controlled clinical trial. J Periodontol 2012b;83:19-26. https://doi.org/10.1902/jop.2011.110206
  17. Wanikar I, Rathod S, Kolte AP. Clinico-radiographic evaluation of 1% alendronate gel as an adjunct and smart blood derivative platelet rich fibrin in grade II furcation defects. J Periodontol 2019;90:52-60. https://doi.org/10.1002/JPER.18-0146
  18. Kanoriya D, Pradeep AR, Garg V, Singhal S. Mandibular degree II furcation defects treatment with platelet-rich fibrin and 1% alendronate gel combination: a randomized controlled clinical trial. J Periodontol 2017;88:250-8. https://doi.org/10.1902/jop.2016.160269
  19. Fernandes LA, Martins TM, Almeida JM, Nagata MJ, Theodoro LH, Garcia VG, et al. Experimental periodontal disease treatment by subgingival irrigation with tetracycline hydrochloride in rats. J Appl Oral Sci 2010;18:635-40. https://doi.org/10.1590/S1678-77572010000600017
  20. Nunes NL, Messora MR, Oliveira LF, Lisboa M, Garcia MC, Rego RO, et al. Effects of local administration of tiludronic acid on experimental periodontitis in diabetic rats. J Periodontol 2018;89:105-16.
  21. Garcia VG, Novaes VC, de Almeida JM, Longo M, Ervolino E, Bomfim SR, et al. Evaluation of the progression and treatment of experimental periodontitis in rats subjected to chemotherapy with 5-fluorouracil. Support Care Cancer 2015;23:2007-17. https://doi.org/10.1007/s00520-014-2563-y
  22. Garcia VG, Longo M, Gualberto Junior EC, Bosco AF, Nagata MJ, Ervolino E, et al. Effect of the concentration of phenothiazine photosensitizers in antimicrobial photodynamic therapy on bone loss and the immune inflammatory response of induced periodontitis in rats. J Periodontal Res 2014;49:584-94. https://doi.org/10.1111/jre.12138
  23. Oz HS, Puleo DA. Animal models for periodontal disease. J Biomed Biotechnol 2011;2011:754857. https://doi.org/10.1155/2011/754857
  24. Sanz M, Teughels WGroup A of European Workshop on Periodontology. Innovations in non-surgical periodontal therapy: consensus report of the Sixth European Workshop on Periodontology. J Clin Periodontol 2008;35:3-7. https://doi.org/10.1111/j.1600-051X.2008.01256.x
  25. Reddy GT, Kumar TM, Veena KM. Formulation and evaluation of alendronate sodium gel for the treatment of bone resorptive lesions in periodontitis. Drug Deliv 2005;12:217-22. https://doi.org/10.1080/10717540590952663
  26. Akram Z, Abduljabbar T, Kellesarian SV, Abu Hassan MI, Javed F, Vohra F. Efficacy of bisphosphonate as an adjunct to nonsurgical periodontal therapy in the management of periodontal disease: a systematic review. Br J Clin Pharmacol 2017;83:444-54. https://doi.org/10.1111/bcp.13147
  27. Baron R, Ferrari S, Russell RG. Denosumab and bisphosphonates: different mechanisms of action and effects. Bone 2011;48:677-92. https://doi.org/10.1016/j.bone.2010.11.020
  28. Halasy-Nagy JM, Rodan GA, Reszka AA. Inhibition of bone resorption by alendronate and risedronate does not require osteoclast apoptosis. Bone 2001;29:553-9. https://doi.org/10.1016/S8756-3282(01)00615-9
  29. Kuroshima S, Go VA, Yamashita J. Increased numbers of nonattached osteoclasts after long-term zoledronic acid therapy in mice. Endocrinology 2012;153:17-28. https://doi.org/10.1210/en.2011-1439
  30. Nagata MJ, Messora MR, Antoniali C, Fucini SE, de Campos N, Pola NM, et al. Long-term therapy with intravenous zoledronate increases the number of nonattached osteoclasts. J Craniomaxillofac Surg 2017;45:1860-7. https://doi.org/10.1016/j.jcms.2017.08.011
  31. Kaynak D, Meffert R, Gunhan M, Gunhan O, Ozkaya O. A histopathological investigation on the effects of the bisphosphonate alendronate on resorptive phase following mucoperiosteal flap surgery in the mandible of rats. J Periodontol 2000;71:790-6. https://doi.org/10.1902/jop.2000.71.5.790
  32. Gong X, Yu W, Zhao H, Su J, Sheng Q. Skeletal site-specific effects of zoledronate on in vivo bone remodeling and in vitro BMSCs osteogenic activity. Sci Rep 2017;7:36129. https://doi.org/10.1038/srep36129
  33. Dobnig H, Hofbauer LC, Viereck V, Obermayer-Pietsch B, Fahrleitner-Pammer A. Changes in the RANK ligand/osteoprotegerin system are correlated to changes in bone mineral density in bisphosphonate-treated osteoporotic patients. Osteoporos Int 2006;17:693-703. https://doi.org/10.1007/s00198-005-0035-4
  34. De Almeida J, Ervolino E, Bonfietti LH, Novaes VC, Theodoro LH, Fernandes LA, et al. Adjuvant therapy with sodium alendronate for the treatment of experimental periodontitis in rats. J Periodontol 2015;86:1166-75. https://doi.org/10.1902/jop.2015.150166
  35. Kim YH, Kim GS, Baek JH. Inhibitory action of bisphosphonates on bone resorption does not involve the regulation of RANKL and OPG expression. Exp Mol Med 2002;34:145-51. https://doi.org/10.1038/emm.2002.21
  36. Brunsvold MA, Chaves ES, Kornman KS, Aufdemorte TB, Wood R. Effects of a bisphosphonate on experimental periodontitis in monkeys. J Periodontol 1992;63:825-30. https://doi.org/10.1902/jop.1992.63.10.825
  37. Kinane DF. Local antimicrobial therapies in periodontal disease. Ann R Australas Coll Dent Surg 2000;15:57-60.
  38. Needleman IG, Pandya NV, Smith SR, Foyle DM. The role of antibiotics in the treatment of periodontitis (Part 2--Controlled drug delivery). Eur J Prosthodont Restor Dent 1995;3:111-7.
  39. Yaffe A, Iztkovich M, Earon Y, Alt I, Lilov R, Binderman I. Local delivery of an amino bisphosphonate prevents the resorptive phase of alveolar bone following mucoperiosteal flap surgery in rats. J Periodontol 1997;68:884-9. https://doi.org/10.1902/jop.1997.68.9.884
  40. Jeffcoat MK, Cizza G, Shih WJ, Genco R, Lombardi A. Efficacy of bisphosphonates for the control of alveolar bone loss in periodontitis. J Int Acad Periodontol 2007;9:70-6.