The Impact of Systemic Drug Therapies (Bisphosphonates and Immunosuppressants) on Dental Implant Success: A clinical review
The Impact of Systemic Drug Therapies on Dental Implant Success
DOI:
https://doi.org/10.31661/gmj.v13iSP1.3666Keywords:
Dental Implants; Bisphosphonates; Immunosuppressants; Osteonecrosis of the Jaw; Osseointegration; Implant SuccessAbstract
Under normal physiological conditions, dental implants are a reliable and effective choice for tooth replacement with high success rates. However, compromised implant success is more closely related to systemic drug therapies like bisphosphonates and immunosuppressants used in patients.
This review aims to identify key patterns of implant success and complications among patients undergoing long-term systemic drug therapy and provide clinical recommendations for optimizing outcomes. Bisphosphonates, especially in their intravenous (IV) forms, inhibit osteoclast activity and decrease bone turnover, which may negatively impact osseointegration and increase the incidence of osteonecrosis of the jaw (ONJ). Immunosuppressants are commonly associated with delayed wound healing and a higher risk of infection, complicating implant osseointegration due to their effect on the immune response. Clinicians must adopt personalized approaches to prevent complications in this patient population. Moreover, future studies should aim to explore the long-term effects of systemic drug therapies, particularly regarding dosages, treatment durations, combinations, and newer medications, while investigating drug interactions and dose-response relationships to provide more specific guidelines for clinicians on implant outcomes.
References
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Bornstein MM, Schmid B, Belser UC, Lussi A, Buser D. Conditions, treatments, and risks of therapy in implant dentistry: a review. Quintessence Int. 2009;40(9):743-53.
Javed F, Almas K. Osseointegration of dental implants in patients undergoing bisphosphonate treatment: a literature review. J Periodontol. 2010;81(4):479-84.
https://doi.org/10.1902/jop.2009.090587
PMid:20367090
Al-Noaman AS. Influence of Oral Bisphosphonate on Dental Implant: A Review. Med J Babylon. 2022 Apr;19(2):180-4.
https://doi.org/10.4103/MJBL.MJBL_96_21
Chadha R, Jalali E, Anwar T. Osseointegration of implants in patients with osteonecrosis of the jaw: A case report. J Maxillofac Oral Surg. 2013;12(3):290-3.
Radzewski R, Osmola K. Osseointegration of Dental Implants in Organ Transplant Patients Undergoing Chronic Immunosuppressive Therapy. Implant Dent. 2019 Oct;28(5):447-54.
https://doi.org/10.1097/ID.0000000000000916
PMid:31306295
Ata-Ali J, Ata-Ali F, Peñarrocha-Oltra D, Galindo-Moreno P. What is the impact of bisphosphonate therapy upon dental implant survival A systematic review and meta-analysis. Clin Oral Implants Res. 2016 Feb;27(2):e38-46.
https://doi.org/10.1111/clr.12526
PMid:25406770
Kafantaris NM. The Impact of Bisphosphonate Therapy Upon Oral Implant Treatment; A Systematic Review. Adv Dent Oral Health. 2016 Dec 14;3(2):555610.
https://doi.org/10.19080/ADOH.2016.03.555610
Famili P, Quigley S, Mosher T. Survival of dental implants among post-menopausal female dental school patients taking oral bisphosphonates: a retrospective study. Compend Contin Educ Dent Jamesburg NJ 1995. 2011;32(6):E106-109.
Shabestari GO, Shayesteh YS, Khojasteh A, Alikhasi M, Moslemi N, Aminian A, et al. Implant Placement in Patients with Oral Bisphosphonate Therapy: A Case Series. Clin Implant Dent Relat Res. 2010 Sep;12(3):175-80.
https://doi.org/10.1111/j.1708-8208.2009.00150.x
PMid:19438964
Kim I, Ki H, Lee W, Kim H, Park J. The effect of systemically administered bisphosphonates on bony healing after tooth extraction and osseointegration of dental implants in a rabbit model. Int J Oral Maxillofac Implants. 2013;28(5):1194-200.
https://doi.org/10.11607/jomi.2685
PMid:24066308
Tsetsenekou E, Papadopoulos T, Kalyvas D, Papaioannou N, Tangl S, Watzek G. The influence of alendronate on osseointegration of nanotreated dental implants in New Zealand rabbits. Clin Oral Implants Res. 2012 Jun;23(6):659-66.
https://doi.org/10.1111/j.1600-0501.2011.02189.x
PMid:21488972
Korn P, Kramer I, Schlottig F, Tödtmann N, Eckelt U, Bürki A, et al. Systemic sclerostin antibody treatment increases osseointegration and biomechanical competence of zoledronic-acid-coated dental implants in a rat osteoporosis model. Eur Cell Mater. 2019 May 21;37:333-46.
https://doi.org/10.22203/eCM.v037a20
PMid:31112281
Inoue M, Matsumoto C, Nakajima K, Kuroshima S, Sawase T. Alendronate/dexamethasone combination therapy worsens soft and hard tissue wound healing around implants in rat maxillae. Bone. 2021 Jul;148:115942.
https://doi.org/10.1016/j.bone.2021.115942
PMid:33836307
Sculean A, Gruber R, Bosshardt DD. Soft tissue wound healing around teeth and dental implants. J Clin Periodontol [Internet]. 2014 Apr [cited 2024 Oct 15];41(s15):12206.
https://doi.org/10.1111/jcpe.12206
Yamazaki T, Yamori M, Ishizaki T, Asai K, Goto K, Takahashi K. Increased incidence of osteonecrosis of the jaw after tooth extraction in patients treated with bisphosphonates: A cohort study. Int J Oral Maxillofac Surg. 2012;41(11):1397-403.
https://doi.org/10.1016/j.ijom.2012.06.020
PMid:22840716
Rai S, Rai A, Kumar T, Kumari M, Somanna M, Bandgar S. Immediately loaded single unit dental implants: A clinical study. J Pharm Bioallied Sci. 2020;12(5):245.
https://doi.org/10.4103/jpbs.JPBS_72_20
PMid:33149465 PMCid:PMC7595488
Thomas JG, Ouanounou A. Medication-related osteonecrosis of the jaw: a narrative review of risk factors, diagnosis, and management. Front Oral Maxillofac Med [Internet]. 2023 Dec 30 [cited 2024 Oct 15];5:106.
https://doi.org/10.21037/fomm-21-106
Liddelow G, Klineberg I. Patient-related risk factors for implant therapy A critique of pertinent literature. Aust Dent J. 2011;56(4):417-26.
https://doi.org/10.1111/j.1834-7819.2011.01367.x
PMid:22126353
Wang H, Weber D, McCauley LK. Effect of Long-Term Oral Bisphosphonates on Implant Wound Healing: Literature Review and a Case Report. J Periodontol. 2007 Mar;78(3):584-94.
https://doi.org/10.1902/jop.2007.060239
PMid:17335384
Wilkinson JM, Little DG. Bisphosphonates in orthopedic applications. Bone. 2011 Jul;49(1):95-102.
https://doi.org/10.1016/j.bone.2011.01.009
PMid:21256254
Scully C, Madrid C, Bagan J. Dental Endosseous Implants in Patients on Bisphosphonate Therapy. Implant Dent. 2006 Sep;15(3):212-8.
https://doi.org/10.1097/01.id.0000236120.22719.02
PMid:16966893
Hokugo A, Kanayama K, Sun S, Morinaga K, Sun Y, Wu Q, et al. Rescue bisphosphonate treatment of alveolar bone improves extraction socket healing and reduces osteonecrosis in zoledronate-treated mice. Bone. 2019 Jun;123:115-28.
https://doi.org/10.1016/j.bone.2019.03.027
PMid:30926440 PMCid:PMC7282713
Holzinger D, Seemann R, Matoni N, Ewers R, Millesi W, Wutzl A. Effect of Dental Implants on Bisphosphonate-Related Osteonecrosis of the Jaws. J Oral Maxillofac Surg. 2014 Oct;72(10):1937.e1-1937.e8.
https://doi.org/10.1016/j.joms.2014.04.037
PMid:25234534
de-Freitas NR, Lima LB, de-Moura MB, Veloso-Guedes C do CF, Simamoto-Júnior PC, de-Magalhães D. Bisphosphonate treatment and dental implants: A systematic review. Med Oral Patol Oral Cir Bucal. 2016 Sep;21(5):e644-51.
https://doi.org/10.4317/medoral.20920
PMid:27475681 PMCid:PMC5005105
Sulaiman N, Fadhul F, Chrcanovic BR. Bisphosphonates and dental implants: A systematic review and meta-analysis. Materials. 2023;16(18):6078.
https://doi.org/10.3390/ma16186078
PMid:37763356 PMCid:PMC10532755
Burtscher D, Torre DD. Dental implant procedures in immunosuppressed organ transplant patients: a systematic review. Int J Oral Maxillofac Surg. 2022 Mar 1;51(3):380-7.
https://doi.org/10.1016/j.ijom.2021.06.008
PMid:34274207
Fireman M, DiMartini AF, Armstrong SC, Cozza KL. Immunosuppressants. Psychosomatics. 2004 Jul;45(4):354-60.
https://doi.org/10.1176/appi.psy.45.4.354
PMid:15232051
Hayashi M, Morimoto Y, Iida T, Tanaka Y, Sugiyama S. Risk of Delayed Healing of Tooth Extraction Wounds and Osteonecrosis of the Jaw among Patients Treated with Potential Immunosuppressive Drugs: A Retrospective Cohort Study. Tohoku J Exp Med. 2018;246(4):257-64.
https://doi.org/10.1620/tjem.246.257
PMid:30568073
Rabbie SC, Martin PD, Flanagan T, Basit AW, Standing JF. Estimating the variability in fraction absorbed as a paradigm for informing formulation development in early clinical drug development. Eur J Pharm Sci. 2016 Jun;89:50-60.
https://doi.org/10.1016/j.ejps.2016.04.005
PMid:27072431
Vinarov Z, Abdallah M, Agundez JAG, Allegaert K, Basit AW, Braeckmans M, et al. Impact of gastrointestinal tract variability on oral drug absorption and pharmacokinetics: An UNGAP review. Eur J Pharm Sci. 2021 Jul;162:105812.
https://doi.org/10.1016/j.ejps.2021.105812
PMid:33753215
Chrcanovic BR, Albrektsson T, Wennerberg A. Dental implants in irradiated versus non-irradiated patients: A meta-analysis. Clin Implant Dent Relat Res. 2014;16(5):784-92.
Sakakura CE, Margonar R, Sartori R, Morais JAND, Marcantonio E. The Influence of Cyclosporin A on Mechanical Retention of Dental Implants Previously Integrated to the Bone: A Study in Rabbits. J Periodontol. 2006 Dec;77(12):2059-62.
https://doi.org/10.1902/jop.2006.050290
PMid:17209791
Radzewski R, Osmola K. The Use of Dental Implants in Organ Transplant Patients Undergoing Immunosuppressive Therapy: An Overview of Publications. Implant Dent. 2016 Aug;25(4):541-6.
https://doi.org/10.1097/ID.0000000000000417
PMid:27002776
Chappuis V, Avila‐Ortiz G, Araújo MG, Monje A. Medication‐related dental implant failure: Systematic review and meta‐analysis. Clin Oral Implants Res. 2018 Oct;29(S16):55-68.
https://doi.org/10.1111/clr.13137
PMid:30328197
Mendes V, Dos Santos GO, Calasans-Maia MD, Granjeiro JM, Moraschini V. Impact of bisphosphonate therapy on dental implant outcomes: An overview of systematic review evidence. Int J Oral Maxillofac Surg. 2019 Mar;48(3):373-81.
https://doi.org/10.1016/j.ijom.2018.09.006
PMid:30314708
Bonacina R, Mariani U, Villa F, Villa A. Preventive strategies and clinical implications for bisphosphonate-related osteonecrosis of the jaw: a review of 282 patients. J Can Dent Assoc. 2011;77(77):b147.
Appoo A, Christensen BL, Somayaji R. Examining the association of immunosuppressants and wound healing: A narrative review. World Counc Enteros Ther J. 2024 Sep;44(3):12-9.
https://doi.org/10.33235/wcet.44.3.12-19/
Khojasteh A, Dehghan MM, Nazeman P. Immediate implant placement following 1-year treatment with oral versus intravenous bisphosphonates: a histomorphometric canine study on peri-implant bone. Clin Oral Investig. 2019 Apr;23(4):1803-9.
https://doi.org/10.1007/s00784-018-2579-7
PMid:30187256
Kim HW, Lee MW, Lee JH, Kim MY. Comparison of the Effect of Oral Versus Intravenous Bisphosphonate Administration on Osteoclastogenesis in Advanced-Stage Medication-Related Osteonecrosis of the Jaw Patients. J Clin Med. 2021 Jul 4;10(13):2988.
https://doi.org/10.3390/jcm10132988
PMid:34279472 PMCid:PMC8268194
Ruggiero SL, Dodson TB, Aghaloo T, Carlson ER, Ward BB, Kademani D. American Association of Oral and Maxillofacial Surgeons' Position Paper on Medication-Related Osteonecrosis of the Jaws-2022 Update. J Oral Maxillofac Surg. 2022 May 1;80(5):920-43.
https://doi.org/10.1016/j.joms.2022.02.008
PMid:35300956
Altalhi AM, Alsubaihi AA, Aldosary MM, Alotaibi LF, Aldosariy NM, Alwegaisi AK, et al. Enhancing the Oral Rehabilitation and Quality of Life of Bisphosphonate-Treated Patients: The Role of Dental Implants. Cureus [Internet]. 2023 Oct 7 [cited 2024 Oct 16];15(10):46654.
https://doi.org/10.7759/cureus.46654
Marx RE. Reconstruction of Defects Caused by Bisphosphonate-Induced Osteonecrosis of the Jaws. J Oral Maxillofac Surg. 2009 May;67(5):107-19.
https://doi.org/10.1016/j.joms.2008.12.007
PMid:19371821
Salgueiro M, Stribos M, Zhang LF, Stevens M, Awad ME, Elsalanty M. Value of pre-operative CTX serum levels in the prediction of medication-related osteonecrosis of the jaw (MRONJ): a retrospective clinical study. EPMA J. 2019 Mar 1;10(1):21-9.
https://doi.org/10.1007/s13167-019-0160-3
PMid:30984311 PMCid:PMC6459452
Brock G, Barker K, Butterworth CJ, Rogers S. Practical considerations for treatment of patients taking bisphosphonate medications: an update. Dent Update. 2011 Jun 2;38(5):313-26.
https://doi.org/10.12968/denu.2011.38.5.313
PMid:21834312
Khan AA, Sándor GKB, Dore E, Morrison AD, Alsahli M, Amin F, et al. Canadian Consensus Practice Guidelines for Bisphosphonate Associated Osteonecrosis of the Jaw. J Rheumatol. 2008 Jul 1;35(7):1391-7.
Goiato MC, Dos Santos DM, Rondon BCS, Moreno A, Baptista GT, Verri FR, et al. Care Required When Using Bisphosphonates in Dental Surgical Practice. J Craniofac Surg. 2010 Nov;21(6):1966-70.
https://doi.org/10.1097/SCS.0b013e3181f5031c
PMid:21119471
Kalra S, Jain V. Dental complications and management of patients on bisphosphonate therapy: A review article. J Oral Biol Craniofacial Res. 2013 Jan;3(1):25-30.
https://doi.org/10.1016/j.jobcr.2012.11.001
PMid:25737876 PMCid:PMC3942225
Abtahi J, Agholme F, Aspenberg P, Tengvall P. A bisphosphonate-coating improves the fixation of metal implants in human bone. Acta Biomater. 2012;8(10):3838-45.
https://doi.org/10.1016/j.bone.2012.02.151
Momand P, Becktor JP, Naimi-Akbar A, Tobin G, Götrick B. Effect of antibiotic prophylaxis in dental implant surgery: A multicenter placebo-controlled double-blinded randomized clinical trial. Clin Implant Dent Relat Res. 2022 Feb;24(1):116-24.
https://doi.org/10.1111/cid.13068
PMid:35075765 PMCid:PMC9306815
Bermúdez-Bejarano EB, Serrera-Figallo MÁ, Gutiérrez-Corrales A, Romero-Ruiz MM, Castillo-de-Oyagüe R, Gutiérrez-Pérez JL, et al. Prophylaxis and antibiotic therapy in management protocols of patients treated with oral and intravenous bisphosphonates. J Clin Exp Dent. 2017 Jan 1;9(1):e141.
Spanou A, Nelson K, Ermer MA, Steybe D, Poxleitner P, Voss PJ. Primary wound closure and perioperative antibiotic therapy for prevention of bisphosphonate-related osteonecrosis of the jaw after tooth extraction. Quintessence Int Berl Ger 1985. 2020;51(3):220-8.
Kim A (Seongju), Abdelhay N, Levin L, Walters JD, Gibson MP. Antibiotic prophylaxis for implant placement: a systematic review of effects on reduction of implant failure. Br Dent J. 2020 Jun;228(12):943-51.
https://doi.org/10.1038/s41415-020-1649-9
PMid:32591710 PMCid:PMC7319948
Matias De Assis G, Queiroz S, Germano A. Systemic Use of Antibiotics in Dental Implant Surgeries in Immunocompetent Patients: A Blind Randomized Controlled Trial. Int J Oral Maxillofac Implants. 2023 Dec 12;38(6):1168-74.
https://doi.org/10.11607/jomi.10115
PMid:38085748
Wang AS, Armstrong EJ, Armstrong AW. Corticosteroids and wound healing: clinical considerations in the perioperative period. Am J Surg. 2013 Sep;206(3):410-7.
https://doi.org/10.1016/j.amjsurg.2012.11.018
PMid:23759697
Hernández G, Paredes V, López-Pintor R. Implant treatment in immunosuppressed renal transplant patients: A prospective case-controlled study. Clin Oral Implants Res. 2019;30(6):524-30.
https://doi.org/10.1111/clr.13437
PMid:30980770
Lazarovici TS, Yahalom R, Taicher S, Schwartz-Arad D, Peleg O, Yarom N. Bisphosphonate-Related Osteonecrosis of the Jaw Associated With Dental Implants. J Oral Maxillofac Surg. 2010 Apr;68(4):790-6.
https://doi.org/10.1016/j.joms.2009.09.017
PMid:20307764
Tenore G, Zimbalatti A, Rocchetti F, Graniero F, Gaglioti D, Mohsen A, et al. Management of Medication-Related Osteonecrosis of the Jaw (MRONJ) Using Leukocyte- and Platelet-Rich Fibrin (L-PRF) and Photobiomodulation: A Retrospective Study. J Clin Med. 2020 Oct 29;9(11):3505.
https://doi.org/10.3390/jcm9113505
PMid:33138266 PMCid:PMC7693575
Romanos GE, Vaglica M, Sculean A. Drug-associated bone resorption with potential dental and implant implications. Periodontol 2000. 2022;90(1):236-46.
https://doi.org/10.1111/prd.12461
PMid:35916776
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