Anchorage, Denosumab, RANKL inhibitor, Tooth movement
Citation Information :
Patil S, Dinesh SP, Sivakumar A, Alshehri A, Awadh W, Patil S. Evaluating the Effect of Denosumab in Preventing Anchorage Loss: A Split-mouth Randomized Controlled Trial. J Contemp Dent Pract 2021; 22 (12):1399-1405.
Aim: The trial was focused on assessing the effect of Denosumab in preventing anchorage loss during en-masse anterior retraction and evaluating its effect on the retraction.
Materials and methods: This was a split-mouth randomized controlled trial. Ten subjects were randomly allocated with equal probability for Denosumab and control interventions in the contralateral quadrants using computer-generated randomization sequence. During the start of retraction, Denosumab (5 mg/0.2 mL) and injectable sterile water were administered locally on the intervention and control sides, respectively. Lateral cephalograms taken during the start of retraction and later in the 3rd and 6th months into retraction were used to evaluate anchorage loss and retraction. Independent sample t-test and Mann-Whitney U test compared anchorage loss and retraction between the two groups in the maxilla and mandible. Paired t-test and Wilcoxon signed-rank test assessed the anchorage loss and retraction during the first and the second 3 months of retraction.
Results: In the maxilla, Denosumab was effective in preventing anchorage loss with a p-value of 0.001 whereas it was not effective in the mandible (p-value—0.172). A significant reduction in anchorage loss was observed with Denosumab in the second 3 months of retraction compared to the first 3 months. There was no significant difference in the retraction among both groups.
Conclusion: Denosumab was effective in minimizing the anchorage loss in the maxilla without affecting the anterior retraction.
Clinical significance: Denosumab can be effectively used for reinforcing anchorage in the maxilla during en-masse anterior retraction.
Geron S, Shpack N, Kandos S, et al. Anchorage loss—a multifactorial response. Angle Orthod 2003;73(6):730–737. DOI: 10.1043/0003- 3219(2003)073<0730:ALMR>2.0.CO;2.
Koyama I, Iino S, Abe Y, et al. Differences between sliding mechanics with implant anchorage and straight-pull headgear and intermaxillary elastics in adults with bimaxillary protrusion. Eur J Orthod 2011;33(2): 126–131. DOI: 10.1093/ejo/cjq047.
Diar-Bakirly S, Feres MFN, Saltaji H, et al. Effectiveness of the transpalatal arch in controlling orthodontic anchorage in maxillary premolar extraction cases: a systematic review and meta-analysis. Angle Orthod 2017;87(1):147–158. DOI: 10.2319/021216-120.1.
Kuroda STE. Risks and complications of miniscrew anchorage in clinical orthodontics. Jpn Dent Sci Rev 2014;50(4):79–85. DOI: 10.1016/j.jdsr.2014.05.001.
Krishnan V, Davidovitch Z. Cellular, molecular, and tissue-level reactions to orthodontic force. Am J Orthod Dentofac Orthop 2006;129(4):469.e1–469.e32. DOI: 10.1016/j.ajodo.2005.10.007.
Suda T, Takahashi N, Udagawa N, et al. Modulation of osteoclast differentiation and function by the new members of the tumor necrosis factor receptor and ligand families. Endocr Rev 1999;20(3):345–357. DOI: 10.1210/edrv.20.3.0367.
Yamaguchi M. RANK/RANKL/OPG during orthodontic tooth movement. Orthod Craniofac Res 2009;12(2):113–119. DOI: 10.1111/j.1601-6343.2009.01444.x.
Theoleyre S, Wittrant Y, Tat SK, et al. The molecular triad OPG/RANK/RANKL: involvement in the orchestration of pathophysiological bone remodeling. Cytokine Growth Factor Rev 2004;15(6):457–475. DOI: 10.1016/j.cytogfr.2004.06.004.
Kouskoura T, Katsaros C, von Gunten S. The potential use of pharmacological agents to modulate orthodontic tooth movement (OTM). Front Physiol 2017;8. DOI: 10.3389/fphys.2017.00067.
Dunn MD, Park CH, Kostenuik PJ, et al. Local delivery of osteoprotegerin inhibits mechanically mediated bone modeling in orthodontic tooth movement. Bone 2007;41(3):446–455. DOI: 10.1016/j.bone.2007.04.194.
Fernández-González FJ, Cañigral A, López-Caballo JL, et al. Recombinant osteoprotegerin effects during orthodontic movement in a rat model. Eur J Orthod 2016;38(4):379–385. DOI: 10.1093/ejo/cjv056.
Fernández-González FJ, López-Caballo JL, Cañigral A, et al. Osteoprotegerin and zoledronate bone effects during orthodontic tooth movement. Orthod Craniofac Res 2016;19(1):54–64. DOI: 10.1111/ocr.12115.
Sydorak I, Dang M, Baxter SJ, et al. Microsphere controlled drug delivery for local control of tooth movement. Eur J Orthod 2019;41(1):1–8. DOI: 10.1093/ejo/cjy017.
Keles A, Grunes B, DiFuria C, et al. Inhibition of tooth movement by osteoprotegerin vs. pamidronate under conditions of constant orthodontic force. Eur J Oral Sci 2007;115(2):131–136. DOI: 10.1111/j.1600-0722.2007.00433.x.
Kanzaki H, Chiba M, Takahashi I, et al. Local OPG gene transfer to periodontal tissue inhibits orthodontic tooth movement. J Dent Res 2004;83(12):920–925. DOI: 10.1177/154405910408301206.
Schieferdecker A, Voigt M, Riecken K, et al. Denosumab mimics the natural decoy receptor osteoprotegerin by interacting with its major binding site on RANKL. Oncotarget 2014;5(16):6647–6653. DOI: 10.18632/oncotarget.2160.
Bone HG, Wagman RB, Brandi ML, et al. 10 years of denosumab treatment in postmenopausal women with osteoporosis: results from the phase 3 randomised FREEDOM trial and open-label extension. Lancet Diabetes Endocrinol 2017;5(7):513–523. DOI: 10.1016/S2213-8587(17)30138-9.
Naomi P. Denosumab for bone loss due to prostate & breast cancer therapies continuing to show promise. Oncol Times 2005;27(24): 36. DOI: 10.1097/01.cot.0000293807.17167.f7.
Meier ME, van der Bruggen W, van de Sande MAJ, et al. Regression of fibrous dysplasia in response to denosumab therapy: a report of two cases. Bone Rep 2021;14:101058. DOI: 10.1016/j.bonr.2021.101058.
Thiruvenkatachari B, Pavithranand A, Rajasigamani K, et al. Comparison and measurement of the amount of anchorage loss of the molars with and without the use of implant anchorage during canine retraction. Am J Orthod Dentofac Orthop 2006;129(4):551–554. DOI: 10.1016/j.ajodo.2005.12.014.
Nair A, Jacob S. A simple practice guide for dose conversion between animals and human. J Basic Clin Pharm 2016;7(2):27. DOI: 10.4103/0976-0105.177703.
Goswami R, Mishra SK, Kochupillai N. Prevalence & potential significance of vitamin D deficiency in Asian Indians. Indian J Med Res 2008;127(3):229–238. PMID: 18497436.
Vasudevan J, Reddy GMM, Jenifer A, et al. Prevalence and factors associated with vitamin D deficiency in Indian children: a hospital based cross sectional study. Pediatr Oncall 2014;11(3):71–76. DOI: 10.7199/ped.oncall.2014.47.
Woods RG. Testing for drug allergy. Aust Prescr 1997;17:62–65. DOI: 10.18773/austprescr.1994.059.
Brockow K, Przybilla B, Aberer W, et al. Guideline for the diagnosis of drug hypersensitivity reactions. Allergo J Int 2015;24(3):94–105. DOI: 10.1007/s40629-015-0052-6.
McNamara JA. A method of cephalometric evaluation. Am J Orthod 1984;86(6):449–469. DOI: 10.1016/S0002-9416(84)90352-X.
Björk A. Prediction of mandibular growth rotation. Am J Orthod 1969;55(6):585–599. DOI: 10.1016/0002-9416(69)90036-0.
Thiruvenkatachari B, Ammayappan P, Kandaswamy R. Comparison of rate of canine retraction with conventional molar anchorage and titanium implant anchorage. Am J Orthod Dentofac Orthop 2008;134(1):30–35. DOI: 10.1016/j.ajodo.2006.05.044.
Ominsky MS, Li X, Asuncion FJ, et al. RANKL inhibition with osteoprotegerin increases bone strength by improving cortical and trabecular bone architecture in ovariectomized rats. J Bone Miner Res 2008;23(5):672–682. DOI: 10.1359/jbmr.080109.
Kostenuik P. Osteoprotegerin and RANKL regulate bone resorption, density, geometry and strength. Curr Opin Pharmacol 2005;5(6): 618–625. DOI: 10.1016/j.coph.2005.06.005.
Park H-S, Lee Y-J, Jeong S-H, et al. Density of the alveolar and basal bones of the maxilla and the mandible. Am J Orthod Dentofac Orthop 2008;133(1):30–37. DOI: 10.1016/j.ajodo.2006.01.044.
Veginadu P, Tavva SR, Muddada V, et al. Effect of pharmacological agents on relapse following orthodontic tooth movement: Angle Orthod 2020;90(4):598–606. DOI: 10.2319/092619-613.1.
Kaklamanos EG, Makrygiannakis MA, Athanasiou AE. Could medications and biologic factors affect post-orthodontic tooth movement changes? A systematic review of animal studies. Orthod Craniofac Res 2021;24(1):39–51. DOI: 10.1111/ocr.12411.
Fujimura Y, Kitaura H, Yoshimatsu M, et al. Influence of bisphosphonates on orthodontic tooth movement in mice. Eur J Orthod 2009;31(6):572–577. DOI: 10.1093/ejo/cjp068.
Ajwa N. The role of bisphosphonates in orthodontic tooth movement—a review. J Fam Med Prim Care 2019;8(12):3783–3788. DOI: 10.4103/jfmpc.jfmpc_825_19.
Kaipatur NR, Wu Y, Adeeb S, et al. Impact of bisphosphonate drug burden in alveolar bone during orthodontic tooth movement in a rat model: a pilot study. Am J Orthod Dentofac Orthop 2013;144(4): 557–567. DOI: 10.1016/j.ajodo.2013.06.015.
Venkataramana V, Chidambaram S, Reddy BV, et al. Impact of bisphosphonate on orthodontic tooth movement and osteoclastic count: an animal study. J Int Oral Heal 2014;6(2):1–8. PMID: 24876695.
Baron R, Ferrari S, Russell RGG. Denosumab and bisphosphonates: different mechanisms of action and effects. Bone 2011;48(4):677–692. DOI: 10.1016/j.bone.2010.11.020.
Dahiya N, Khadka A, Sharma AK, et al. Denosumab: a bone antiresorptive drug. Med J Armed Forces India 2015;71(1):71–75. DOI: 10.1016/j.mjafi.2014.02.001.