Teriparatide on Maxillary Sinus Floor Osseointegration

Summary

The aim of this triple blind randomized controlled trial will be to analyze the effect of a dose of teriparatide combined with a xenograft on bone augmentation of the maxillary sinus, to observe the microarchitecture of the newly formed bone and the primary and late stability of implants placed on these grafts. The sample is composed of 42 participants who have a clinical indication for maxillary sinus floor augmentation with bone grafting due to residual bone height less than or equal to 5mm for the installation of dental implants. Each side will be grafted with Bio-Oss® or Bio-Oss® combined with 1 dose (20 µg) of teriparatide (Forteo®). Three months after grafting, at the time of placement of dental implants, bone biopsies will be obtained using a short 2mm trephine bur. These bone cores will be submitted to histological and histomorphometric analysis. The stability of the implants will be measured, at the time of their installation, through the insertion torque, and through the use of resonance frequency equipment (Ostell®) in three moments: immediately and at 3 and 6 months after the installation of the dental implants.

Timeline

Start

2023-08-23

Primary completion

2024-08

Completion

2024-12

Publications

• Background Miller SC, Hunziker J, Mecham M, Wronski TJ. Intermittent parathyroid hormone administration stimulates bone formation in the mandibles of aged ovariectomized rats. J Dent Res. 1997 Aug;76(8):1471-6. doi: 10.1177/00220345970760080901.
• Background Boabaid F, Berry JE, Koh AJ, Somerman MJ, McCcauley LK. The role of parathyroid hormone-related protein in the regulation of osteoclastogenesis by cementoblasts. J Periodontol. 2004 Sep;75(9):1247-54. doi: 10.1902/jop.2004.75.9.1247.
• Background Jung RE, Cochran DL, Domken O, Seibl R, Jones AA, Buser D, Hammerle CH. The effect of matrix bound parathyroid hormone on bone regeneration. Clin Oral Implants Res. 2007 Jun;18(3):319-25. doi: 10.1111/j.1600-0501.2007.01342.x. Epub 2007 Mar 26.
• Background Liu J, Cao Z, Li C. Intermittent PTH administration: a novel therapy method for periodontitis-associated alveolar bone loss. Med Hypotheses. 2009 Mar;72(3):294-6. doi: 10.1016/j.mehy.2008.10.015. Epub 2008 Nov 30.
• Background Rowshan HH, Parham MA, Baur DA, McEntee RD, Cauley E, Carriere DT, Wood JC, Demsar WJ, Pizarro JM. Effect of intermittent systemic administration of recombinant parathyroid hormone (1-34) on mandibular fracture healing in rats. J Oral Maxillofac Surg. 2010 Feb;68(2):260-7. doi: 10.1016/j.joms.2009.09.045.
• Background Valderrama P, Jung RE, Thoma DS, Jones AA, Cochran DL. Evaluation of parathyroid hormone bound to a synthetic matrix for guided bone regeneration around dental implants: a histomorphometric study in dogs. J Periodontol. 2010 May;81(5):737-47. doi: 10.1902/jop.2010.090562.
• Background Zeng X, He H, Zhang L, Wu Y, Wang Y, Gong P. A potential therapeutic approach to overload-induced bone loss around implant: parathyroid hormone (PTH). Med Hypotheses. 2011 Nov;77(5):701-4. doi: 10.1016/j.mehy.2011.06.016. Epub 2011 Sep 9.
• Background Kuchler U, Luvizuto ER, Tangl S, Watzek G, Gruber R. Short-term teriparatide delivery and osseointegration: a clinical feasibility study. J Dent Res. 2011 Aug;90(8):1001-6. doi: 10.1177/0022034511407920. Epub 2011 May 9.
• Background Ali MN, Kobayashi T, Tanaka M, Ohshima H, Ejiri S, Saito C. Effects of intermittent parathyroid hormone treatment on new bone formation during distraction osteogenesis in the rat mandible. Oral Surg Oral Med Oral Pathol Oral Radiol. 2012 Jul;114(1):e36-42. doi: 10.1016/j.oooo.2011.08.009. Epub 2012 Feb 25.
• Background Aggarwal P, Zavras A. Parathyroid hormone and its effects on dental tissues. Oral Dis. 2012 Jan;18(1):48-54. doi: 10.1111/j.1601-0825.2011.01850.x. Epub 2011 Sep 6.
• Background Wolf M, Lossdorfer S, Abuduwali N, Meyer R, Kebir S, Gotz W, Jager A. Effect of intermittent PTH(1-34) on human periodontal ligament cells transplanted into immunocompromised mice. Tissue Eng Part A. 2012 Sep;18(17-18):1849-56. doi: 10.1089/ten.TEA.2011.0626. Epub 2012 May 21.
• Background Chan HL, McCauley LK. Parathyroid hormone applications in the craniofacial skeleton. J Dent Res. 2013 Jan;92(1):18-25. doi: 10.1177/0022034512464779. Epub 2012 Oct 15.
• Background Kuroshima S, Kovacic BL, Kozloff KM, McCauley LK, Yamashita J. Intra-oral PTH administration promotes tooth extraction socket healing. J Dent Res. 2013 Jun;92(6):553-9. doi: 10.1177/0022034513487558. Epub 2013 Apr 23.
• Background Kuroshima S, Al-Salihi Z, Yamashita J. Parathyroid hormone related to bone regeneration in grafted and nongrafted tooth extraction sockets in rats. Implant Dent. 2013 Feb;22(1):71-6. doi: 10.1097/ID.0b013e318278f94d.
• Background Lima LL, Cesar Neto JB, Cayana EG, Nociti FH Jr, Sallum EA, Casati MZ. Parathyroid hormone (1-34) compensates the negative effect of smoking around implants. Clin Oral Implants Res. 2013 Sep;24(9):1055-9. doi: 10.1111/j.1600-0501.2012.02502.x. Epub 2012 Jun 19.
• Background Tang ZL, Zhang WJ, Wang DX, Chen JM, Ma H, Wu DR. An experimental study addressing the promotion of mandibular defect repair through the intermittent subcutaneous injection of parathyroid hormone. J Oral Maxillofac Surg. 2014 Feb;72(2):419-30. doi: 10.1016/j.joms.2013.07.037. Epub 2013 Sep 24.
• Background Vasconcelos DF, Marques MR, Benatti BB, Barros SP, Nociti FH Jr, Novaes PD. Intermittent parathyroid hormone administration improves periodontal healing in rats. J Periodontol. 2014 May;85(5):721-8. doi: 10.1902/jop.2013.130155. Epub 2013 Jul 29.
• Background Ersan N, van Ruijven LJ, Bronckers AL, Olgac V, Ilguy D, Everts V. Teriparatide and the treatment of bisphosphonate-related osteonecrosis of the jaw: a rat model. Dentomaxillofac Radiol. 2014;43(1):20130144. doi: 10.1259/dmfr.20130144. Epub 2013 Oct 29.
• Background Kakehashi H, Ando T, Minamizato T, Nakatani Y, Kawasaki T, Ikeda H, Kuroshima S, Kawakami A, Asahina I. Administration of teriparatide improves the symptoms of advanced bisphosphonate-related osteonecrosis of the jaw: preliminary findings. Int J Oral Maxillofac Surg. 2015 Dec;44(12):1558-64. doi: 10.1016/j.ijom.2015.07.018. Epub 2015 Aug 21.
• Background Tsunori K. Effects of parathyroid hormone dosage and schedule on bone regeneration. J Oral Sci. 2015 Jun;57(2):131-6. doi: 10.2334/josnusd.57.131.
• Background Otawa M, Tanoue R, Kido H, Sawa Y, Yamashita J. Intermittent administration of parathyroid hormone ameliorates periapical lesions in mice. J Endod. 2015 May;41(5):646-51. doi: 10.1016/j.joen.2014.12.008. Epub 2015 Jan 30.
• Background Keskinruzgar A, Bozdag Z, Aras MH, Demir T, Yolcu U, Cetiner S. Histopathological Effects of Teriparatide in Medication-Related Osteonecrosis of the Jaw: An Animal Study. J Oral Maxillofac Surg. 2016 Jan;74(1):68-78. doi: 10.1016/j.joms.2015.07.005. Epub 2015 Jul 14.
• Background dos Santos RA, Ferreira MS, Mafra CE, Holzhausen M, de Lima LA, Mendes Pannuti C, Cesar Neto JB. Synthetic Parathyroid Hormone May Augment Bone Volume in Autogenous Grafts: A Study in Rats. J Periodontol. 2016 Jan;87(1):66-73. doi: 10.1902/jop.2015.140638. Epub 2015 Sep 25.
• Background Javed F, Al Amri MD, Kellesarian SV, Al-Kheraif AA, Vohra F, Calvo-Guirado JL, Malmstrom H, Romanos GE. Efficacy of parathyroid hormone supplementation on the osseointegration of implants: a systematic review. Clin Oral Investig. 2016 May;20(4):649-58. doi: 10.1007/s00784-015-1691-1. Epub 2015 Dec 22.
• Background Zandi M, Dehghan A, Mohammadi-Mofrad A, Amini P, Vahdatinia F. Short-term perioperative teriparatide therapy for the prevention of medication-related osteonecrosis of the jaw: A randomized, controlled preclinical study in rats. J Craniomaxillofac Surg. 2017 Feb;45(2):275-280. doi: 10.1016/j.jcms.2016.12.010. Epub 2016 Dec 19.
• Background Zandi M, Dehghan A, Zandipoor N, Amini P, Doulati S. Effect of different doses and durations of teriparatide therapy on resolution of medication-related osteonecrosis of the jaw: A randomized, controlled preclinical study in rats. J Craniomaxillofac Surg. 2018 Mar;46(3):466-472. doi: 10.1016/j.jcms.2017.12.027. Epub 2017 Dec 30.
• Background Goker F, Ersanli S, Arisan V, Cevher E, Guzel EE, Issever H, Omer B, Durmus Altun G, Morina D, Ekiz Yilmaz T, Dervisoglu E, Del Fabbro M. Combined effect of parathyroid hormone and strontium ranelate on bone healing in ovariectomized rats. Oral Dis. 2018 Oct;24(7):1255-1269. doi: 10.1111/odi.12895. Epub 2018 Jun 11.
• Background Zandi M, Dehghan A, Amini P, Doulati S, Rezaeian L. Evaluation of the effect of teriparatide therapy on mandibular fracture healing in rats with medication-related osteonecrosis of the jaw. Clin Oral Investig. 2019 Nov;23(11):3987-3993. doi: 10.1007/s00784-019-02830-2. Epub 2019 Feb 4.
• Background Yoshida W, Matsugami D, Murakami T, Bizenjima T, Imamura K, Seshima F, Saito A. Combined effects of systemic parathyroid hormone (1-34) and locally delivered neutral self-assembling peptide hydrogel in the treatment of periodontal defects: An experimental in vivo investigation. J Clin Periodontol. 2019 Oct;46(10):1030-1040. doi: 10.1111/jcpe.13170.
• Background Zandi M, Dehghan A, Gheysari F, Rezaeian L, Mohammad Gholi Mezerji N. Evaluation of teriparatide effect on healing of autografted mandibular defects in rats. J Craniomaxillofac Surg. 2019 Jan;47(1):120-126. doi: 10.1016/j.jcms.2018.11.015. Epub 2018 Nov 23.
• Background de Oliveira D, de Oliveira Puttini I, Silva Gomes-Ferreira PH, Palin LP, Matsumoto MA, Okamoto R. Effect of intermittent teriparatide (PTH 1-34) on the alveolar healing process in orchiectomized rats. Clin Oral Investig. 2019 May;23(5):2313-2322. doi: 10.1007/s00784-018-2672-y. Epub 2018 Oct 6.
• Background Li Y, Chen XY, Tang ZL, Tan JQ, Wang DX, Dong Q. Differences in accelerated tooth movement promoted by recombinant human parathyroid hormone after mandibular ramus osteotomy. Am J Orthod Dentofacial Orthop. 2019 May;155(5):670-680. doi: 10.1016/j.ajodo.2018.06.014.
• Background Zandi M, Dehghan A, Bigonah N, Doulati S, Mohammad Gholi Mezerji N. Histological assessment of the effects of teriparatide therapy on mandibular fracture healing: A preclinical study. J Craniomaxillofac Surg. 2020 Mar;48(3):211-216. doi: 10.1016/j.jcms.2020.01.006. Epub 2020 Jan 21.
• Background Zhang C, Li T, Zhou C, Huang L, Li Y, Wang H, Duan P, Zou S, Mei L. Parathyroid hormone increases alveolar bone homoeostasis during orthodontic tooth movement in rats with periodontitis via crosstalk between STAT3 and beta-catenin. Int J Oral Sci. 2020 Dec 30;12(1):38. doi: 10.1038/s41368-020-00104-2.
• Background Pelled G, Lieber R, Avalos P, Cohn-Schwartz D, Tawackoli W, Roth J, Knapp E, Schwarz EM, Awad HA, Gazit D, Gazit Z. Teriparatide (recombinant parathyroid hormone 1-34) enhances bone allograft integration in a clinically relevant pig model of segmental mandibulectomy. J Tissue Eng Regen Med. 2020 Aug;14(8):1037-1049. doi: 10.1002/term.3075. Epub 2020 Jun 25.
• Background Dam C, Jung UW, Park KM, Huh J, Park W. Effect of teriparatide on early sinus graft healing in the ovariectomized rabbit. Clin Oral Implants Res. 2020 Mar;31(3):264-273. doi: 10.1111/clr.13565. Epub 2020 Jan 3.
• Background Stutz C, Batool F, Petit C, Strub M, Kuchler-Bopp S, Benkirane-Jessel N, Huck O. Influence of parathyroid hormone on periodontal healing in animal models: A systematic review. Arch Oral Biol. 2020 Dec;120:104932. doi: 10.1016/j.archoralbio.2020.104932. Epub 2020 Oct 6.
• Background Emam H, Leach D, Sun Z, Tee BC, Karatas B, Kim DG, Jatana C. The Effect of Parathyroid Hormone Analogues When Added to Mineralized Bone Xenografts. J Oral Implantol. 2020 Aug 1;46(4):372-379. doi: 10.1563/aaid-joi-D-19-00016.
• Background Koca CG, Kosehasanogullari M. Evaluation of single-dose applied teriparatide effect on bone healing with histomorphometric and micro-ct analysis. J Craniomaxillofac Surg. 2021 Feb;49(2):98-103. doi: 10.1016/j.jcms.2020.12.004. Epub 2020 Dec 17.
• Background Jung J, Shim GJ, Kim M, Yoon Y, Kim JE, Jue SS, Al-Nawas B, Kwon YD. Effect and timing of parathyroid hormone analog administration for preventing medication-related osteonecrosis of the jaws in a murine model. J Craniomaxillofac Surg. 2021 Aug;49(8):719-725. doi: 10.1016/j.jcms.2021.02.023. Epub 2021 Feb 26.
• Background Anabtawi M, Tweedale H, Mahmood H. The role, efficacy and outcome measures for teriparatide use in the management of medication-related osteonecrosis of the jaw. Int J Oral Maxillofac Surg. 2021 Apr;50(4):501-510. doi: 10.1016/j.ijom.2020.07.021. Epub 2020 Aug 14.
• Background Ebrahimi S, Navabazam A, Salemi F, Khaleghi F, Barzegar M, Saghafi F, Fallahzadeh H. The efficacy of teriparatide (Cinnopar(R)) on bone repair in mandibular fractures: A single blinded randomized clinical trial. J Craniomaxillofac Surg. 2022 Dec;50(12):923-928. doi: 10.1016/j.jcms.2022.12.002. Epub 2023 Jan 5.
• Background Grossi JRA, Deliberador TM, Giovanini AF, Zielak JC, Sebastiani A, Gonzaga CC, Coelho PG, Zetola AL, Weiss FP, Benalcazar Jalkh EB, Storrer CLM, Witek L. Effects of local single dose administration of parathormone on the early stages of osseointegration: A pre-clinical study. J Biomed Mater Res B Appl Biomater. 2022 Aug;110(8):1806-1813. doi: 10.1002/jbm.b.35038. Epub 2022 Feb 26.
• Background Camili Y, Malkoc S, Taslidere A, Ileri Z, Guler OC. Effects of teriparatide on bone formation in rats with experimentally induced premaxillary expansion. Dental Press J Orthod. 2022 Jul 4;27(3):e2220370. doi: 10.1590/2177-6709.27.3.e2220370.oar. eCollection 2022.
• Background Li Y, Qian Y, Qiao H, Pan W, Xie L, Li Y. Abaloparatide outperforms teriparatide in protecting against alveolar bone loss in experimental periodontitis. J Periodontol. 2023 Feb;94(2):244-255. doi: 10.1002/JPER.22-0211. Epub 2022 Nov 8.

Drugs

Indications

No indication recorded.