|
| |
 |
|
| ORIGINAL ARTICLE |
|
| Year : 2022 | Volume
: 19
| Issue : 2 | Page : 180-184 |
|
Influence of oral bisphosphonate on dental implant: A review
Ahmed Salah Al-Noaman
Department of Oral Surgery, College of Dentistry, University of Babylon, Babylon City, Iraq
| Date of Submission | 04-Nov-2021 |
| Date of Acceptance | 11-Jan-2022 |
| Date of Web Publication | 30-Jun-2022 |
Correspondence Address:
Ahmed Salah Al-Noaman
Department of Oral Surgery, College of Dentistry, University of Babylon, Babylon City
Iraq
 Source of Support: None, Conflict of Interest: None
DOI: 10.4103/MJBL.MJBL_96_21
Background: Bisphosphonates (BPs) are medications employed widely in the management of metabolic bone diseases. Dental implants are new therapy for replacement of missing teeth depend on the osseointegration process. There is a considerable debate on the effect of oral BPs on the osseointegration process and subsequently on the success rate of dental implant and development of BRNOJ. Objectives: The aim of this study was to revise literatures on the effect of oral (BPs) on the success rate of dental implants and the development of BPs-related osteonecrosis of the jaws. Materials and Methods: PubMed, google scholar, Scopus database, and manual search were performed to find out articles on the effect of oral BPs on dental implant outcome and development of BRNOJ. Results: twelve articles were found six retrospective studies, one prospective studies, two case control studies and one case series discussing the effect of oral BPs on success rate of dental implant and development of BRNOJ. Conclusion: the majority of patients were osteoporotic females and treated with oral BPs. Oral BPs have little, if any, influence on success rate of dental implant and there is no conclusive evidence on BRNOJ-related oral BPs in implanted patients. Patients on BPs and received implant therapy should be cautioned on developing BRNOJ and followed-up for long time period. Keywords: BRNUJ, dental implant, oral bisphosphonate, osseointegration
How to cite this article:
Al-Noaman AS. Influence of oral bisphosphonate on dental implant: A review. Med J Babylon 2022;19:180-4 |
| Introduction | |  |
Bisphosphonates (BPs) are medications employed widely in the management of metabolic bone diseases like osteoporosis, Paget’s diseases and other conditions associated with bone-lytic tumors, multiple myeloma and hypercalcemia.[1] The chemical structure of these compounds includes the replacement of oxygen atoms with those of carbon, which is similar to the naturally occurring inorganic pyrophosphate. These compounds targeted specifically bone due to a high affinity to calcium phosphate and not-completely metabolized.[2] The exact mechanism of action of such compounds are still vague, but they are known to inhibit osteoclastic activity and their differentiation from precursors, to stimulate apoptosis of osteoclasts and to change angiogenesis.[3] Due to a potential bond with bone minerals (hydroxyapatite), these compounds accumulate and remain for long time in bone and circulation after stop taking the drugs.[4] Hence, as bisphosphonates are slowly released from bone minerals, their action to suppress bone turnover continue even after cessation of therapy.[5]
One of the serious side effects of these compounds is the avascular bone necrosis of the maxilla and the mandible. By definition BP-related bone necrosis is the current or previous treatment with BPs that exposes the upper and lower jaws to the oral cavity and does not cure within 2 months of identification by oral health staff and the patient does not have a history of radiotherapy in the maxillofacial region.[6] The eight weeks period is the timetable for healing of the most surgical and infectious sites even in the presence of complications such as post-operative infection, chemotherapy, or systemic illnesses.[7] Osteonecrosis is usually affecting the upper and lower jaws due to the rapid remodeling rate of alveolar ridge and their exposure to the external environment through teeth.[8]
Dental implant is a device used to replace single or multiple missing teeth. The success rate of dental implant depends on the osseointegration process. This process is defined as the direct attachment between living bone and the implant surface with the capacity of bearing functional load.[9] One of the factors that influencing osseointegration process is the bone density and structure which are strongly correlated with the success rate of dental implant.
Studies revealed that BPs improve bone density around dental implants and subsequently osseointegration process.[10],[11] In theory, this action could be explained by decreasing osteoblastic bone resorption and subsequent reduction in bone remodeling. However, it has been shown that people taking BPs could experience a bad prognosis of dental treatment, particularly after surgery of dental implants.[12]
The skeletal uptake of these medications could be influenced by the route of administration. It has been found that orally administered BPs are poorly absorbed and represent less than 1% of bioavailability, whereas the intravenous are totally bioavailable.[13] Therefore, the hazard of developing bone necrosis is highly attributed to I.V administration.[14] However, the incidence of BRONJ associated with oral BPs have been increased in time.[15] The most common Oral BPs that employed nowadays are alendronate, risedronate, etidronate, tiludronate.[16] Though, some BPs can be administered by oral and intra-venous routes.
The aim of this review was to investigate the literature that considered patients who received oral BPs and treated with dental implants before or after BPs therapy. These articles compared between healthy persons and those who submitted for BPs administration and the outcome of dental implants was based on failure of dental implants or the development of BP- associated osteonecrosis of the jaws (BRNOJ).
| Materials and Methods | | |
Articles on the use of oral BPs and their effect on dental implants outcome have been collected from October 15, 2020 to June, 2021. An electronic PubMed, google scholar, Scopus database and manual search were performed to collect articles and case series relevant to this review. The key words or terms used for searching the articles and case series include bisphosphonate, dental implant, oral bisphosphonate, osteonecrosis, implant failure, bone density. The inclusion criteria include original articles, studies using adult patients, articles discussed the use of oral BPs accompanied with dental implant treatment (before or after), articles published in English language. The exclusion criteria involve studies using patients under the age of 17 years and more than 92 years old, in vitro animal studies, systemic reviews, a sample size of less than 12 patients, studies conducted before 2005 and studies using IV BPs.
The articles were analyzed according to the type of study, number of cases/control, sex distribution, number of implants/control, age of patients, type of drug, duration of treatment, reason for treatment, implant success rate (clinically and radiographically) /control, and follow-up period.
| Ethical consideration | | |
The study was conducted in accordance with the ethical principles that have their origin in the Declaration of Helsinki. It was carried out with patients verbal and analytical approval before sample was taken. The study protocol and the subject information and consent form were reviewed and approved by a local ethics committee according to the document number 111 (including the number and the date in 13/08/2020) to get this approval.
| Results | | |
Twelve original articles were chosen to carry out a review on the influence of oral BPs on outcomes of dental implant treatment. The included articles were chosen according to the inclusion and exclusion criteria of this study.
There are seven articles include retrospective studies, one prospective study, two case controlled studies and two a case series. Meta-analysis was not performed as the number of articles was low and there are variation in the implant procedure (bone graft or sinus lift) and implant numbers inserted in the upper and lower jaws. The evaluation was determined according to the outcome of implant surgery in patients under medical treatment of oral BPs and those of healthy patients. Dental implant outcomes were evaluated clinically and radiographically according to the reviewed articles and included implant failure, success rate and development of BRONJ. Details of each study are depicted in [Table 1].
| Discussion | | |
Some research indicated that oral BPs have no effect on dental implant treatment and there is no clear evidence correlates between the development of BRONJ and implant procedures.[17],[18] However, others stated that these drugs could be the reason behind implant failure and the evolution of BRONJ.[19] Therefore, there is still a considerable debate on the impact of oral BPs on the dental implant therapy and the development of bone necrosis.
The majority of patients included in this review were osteoporotic females with age range 40–91 years old. Females are more submitted for oral BPs therapy after cessation of menstruation and to a greater rate of breast tumor and osteoporosis.[20] It has been shown that age, sex and early menopause among the risk factors of osteoporosis[21] and these factors are similar to those influence failed bone-implant integration. However, Two studies in this review[22],[23] revealed that oral BPs were used for the treatment of osteoporosis, multiple myeloma and breast cancer. Oral BPs prevent bone resorption by inhibiting osteoclasts activity and bone turnover for this reason they employed as a remedy of osteoporosis and other metabolic bone disorders.[24],[25] Besides, these medications enhance bone mineral density and subsequently prevent bone fracture due to osteoporosis.[15]
Most studies[2],[21],[26],[27],[28],[29] in this review indicated the success rate of dental implants was ranged between 95–100%. Gross et al,[30] found that the failure rate of implant was 0.89% among those taking oral BPs. Others,[31],[32] reported early failure of dental implant but there is no significant differences between the control groups and patients on BPs. However, Yip et al,[33] stated that implant success rate decreased to 66.7% in-patient taking oral BPs and most of the failures occurred in the maxilla compared with those in the mandible. Oral BPs might be beneficial for successful osseointegration, as they improve bone mineral density around dental implant.[10],[11] However, such medications may affect negatively implant stability even in the absence of BRONJ, as BPs increase the amount of cancellous bone and decrease that of cortical bone.[32] Moreover, these drugs inhibit bone remodeling which is essential for healing process after surgical trauma of implant insertion.[15]
Only two studies[22],[23] in this review reported the development of BRNOJ-related oral BPs in implanted patients. Kwon et al,[22] in their prospective study reported 19 cases of BRNOJ after implant insertion. In fact, only 3 cases out of 19 of BRONJ were regarded as BRNOJ-associated dental implants, as oral BPs were administered after implant surgery and the lesion was diagnosed 13–27 months after BPs initiation. Lazarovici et al,[23] identified 11 out of 27 cases of BRNOJ-associated oral BPs developed after implant surgery. Apparently, these studies revealed that bone necrosis occurred after long course treatment of oral BPs. However, it is difficult to draw a definitive conclusion based on two studies to blame oral BPs for the establishment of BRNOJ due to implant surgery. Besides, these studies did not mention information on other drugs taken by the patients, precise doses of oral BPs and the exact time of the follow-up stage. It has been stated that the development of BRNOJ is not only associated with type, dose and duration of BPs administration, but also there are other factors such as systemic diseases, genetic factors, anatomical position,[15] smoking, corticosteroid intake and periodontal diseases.[34]
In order to explain the pathogenesis of BRNOJ-associated oral BPs due to implant surgery, Yarum and his co-workers[35] suggested that surgical trauma associated with implant insertion combined with the possible inhibition of bone remodeling may cause the development of BRONJ. In addition to that, these drugs inhibit proliferation of keratinocyte in the oral mucosa and soft tissue injury during implant placement may increase the risk of BRNOJ.[15] Jacobson et al,[36] stated that the presence of implant itself may contribute to the development of BRNOJ and not only the implant surgery.
It is mandatory that patients under medical treatment of oral BPs and seek dental implant therapy should be cautioned on the possibility of developing BRNOJ. Particularly, those suffering from osteoporosis, as these medications may improve bone mineral density but increase the possibility of bone necrosis. Furthermore, those patients who received implant therapy and on oral BPs should be followed-up for long time period.
| Conclusion | | |
The majority of patients treated with oral BPs were females and suffering from osteoporosis. Oral BPs exert little, if any, influence on success rate of dental implants. It is difficult to draw a definitive conclusion on BRNOJ- related Oral BPs in implanted patients. Patients under medical treatment of BPs should be cautioned on the possibility of developing BRONJ as a results of implant placement and should be followed-up for long time period.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
| References | | |
| 1. | Gelazius R, Poskevicius L, Sakavicius D, Grimuta V, Juodzbalys G Dental implant placement in patients on bisphosphonate therapy: A systematic review. J Oral Maxillofac Res 2018;9:e2.  |
| 2. | Demarosi F, Carrassi A, Leghissa G Dental implant treatment in oral bisphosphonates patients using a drug holiday protocol: A prospective study. J Osseointegration 2010;2:73-8. |
| 3. | Russell RG, Watts NB, Ebetino FH, Rogers MJ Mechanisms of action of bisphosphonates: Similarities and differences and their potential influence on clinical efficacy. Osteoporos Int 2008;19:733-59. |
| 4. | Bone HG, Hosking D, Devogelaer JP, Tucci JR, Emkey RD, Tonino RP, et al; Alendronate Phase III Osteoporosis Treatment Study Group. Ten years’ experience with alendronate for osteoporosis in postmenopausal women. N Engl J Med 2004;350:1189-99. |
| 5. | Watts NB, Chines A, Olszynski WP, McKeever CD, McClung MR, Zhou X, et al. Fracture risk remains reduced one year after discontinuation of risedronate. Osteoporos Int 2008;19:365-72. |
| 6. | Khosla S, Burr D, Cauley J, Dempster DW, Ebeling PR, Felsenberg D, et al; American Society for Bone and Mineral Research. Bisphosphonate-associated osteonecrosis of the jaw: Report of a task force of the american society for bone and mineral research. J Bone Miner Res 2007;22:1479-91. |
| 7. | Mohit G, Niha G Bisphosphonate Related Jaw Osteonecrosis. In: StatPearls [Internet]. Treasure Island, FL: StatPearls; 2020: p. 30521192. |
| 8. | Marx RE Pamidronate (aredia) and zoledronate (zometa) induced avascular necrosis of the jaws: A growing epidemic. J Oral Maxillofac Surg 2003;61:1115-7. |
| 9. | Brånemark PI, Breine U, Adell R, Hansson B, Lindström J, Ohlsson Å, Intra-osseous anchorage of dental prostheses: I. Experimental studies. Scand J Plast Reconstr Surg 2009;3:81-100. |
| 10. | Giro G, Gonçalves D, Sakakura CE, Pereira RM, Marcantonio Júnior E, Orrico SR Influence of estrogen deficiency and its treatment with alendronate and estrogen on bone density around osseointegrated implants: Radiographic study in female rats. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2008;105:162-7. |
| 11. | Yildiz A, Esen E, Kürkçü M, Damlar I, Dağlioğlu K, Akova T Effect of zoledronic acid on osseointegration of titanium implants: An experimental study in an ovariectomized rabbit model. J Oral Maxillofac Surg 2010;68:515-23. |
| 12. | Chugh T, Jain AK, Jaiswal RK, Mehrotra P, Mehrotra R Bone density and its importance in orthodontics. J Oral Biol Craniofac Res 2013;3:92-7. |
| 13. | Drake MT, Clarke BL, Lewiecki EM The pathophysiology and treatment of osteoporosis. Clin Ther 2015;37:1837-50. |
| 14. | Diachkova E, Abramova EV, Blagushina NA, Tarasenko S Surgical treatment with dental implants in a patient with secondary loss of teeth and osteoporosis caused by an imbalance of vitamin D. BMJ Case Rep 2020;13:e235585. |
| 15. | Coskun Benlidayi I, Guzel R Oral bisphosphonate related osteonecrosis of the jaw: A challenging adverse effect. Isrn Rheumatol 2013;2013:215034. |
| 16. | Montoya-Carralero JM, Parra-Mino P, Ramírez-Fernández P, Morata-Murcia IM, Mompeán-Gambín MC, Calvo-Guirado JL Dental implants in patients treated with oral bisphosphonates: A bibliographic review. Med Oral Patol Oral Cir Bucal 2010;15:e65-9. |
| 17. | Bornstein MM, Cionca N, Mombelli A Systemic conditions and treatments as risks for implant therapy. Int J Oral Maxillofac Implants 2009;24 (suppl):12-27. |
| 18. | Grant BT, Amenedo C, Freeman K, Kraut RA Outcomes of placing dental implants in patients taking oral bisphosphonates: A review of 115 cases. J Oral Maxillofac Surg 2008;66:223-30. |
| 19. | Flichy-Fernández AJ, Balaguer-Martínez J, Peñarrocha-Diago M, Bagán JV Bisphosphonates and dental implants: Current problems. Med Oral Patol Oral Cir Bucal 2009;14:E355-60. |
| 20. | Maciel AP, Quispe RA, Martins LJO, Caldas RJ, Santos PSDS Clinical profile of individuals with bisphosphonate-related osteonecrosis of the jaw: An integrative review. Sao Paulo Med J 2020;138:326-35. |
| 21. | Jeffcoat MK Safety of oral bisphosphonates: Controlled studies on alveolar bone. Int J Oral Maxillofac Implants 2006;21:349-53. |
| 22. | Kwon TG, Lee CO, Park JW, Choi SY, Rijal G, Shin HI Osteonecrosis associated with dental implants in patients undergoing bisphosphonate treatment. Clin Oral Implants Res 2014;25:632-40. |
| 23. | 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;68:790-6. |
| 24. | Drake MT, Clarke BL, Khosla S Bisphosphonates: Mechanism of action and role in clinical practice. Mayo Clin Proc 2008;83:1032-45. |
| 25. | Rodan GA, Reszka AA Bisphosphonate mechanism of action. Curr Mol Med 2002;2:571-7. |
| 26. | Bell BM, Bell RE Oral bisphosphonates and dental implants: A retrospective study. J Oral Maxillofac Surg 2008;66:1022-4. |
| 27. | Zahid TM, Wang BY, Cohen RE Influence of bisphosphonates on alveolar bone loss around osseointegrated implants. J Oral Implantol 2011;37:335-46. |
| 28. | 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;12:175-80. |
| 29. | Fugazzotto PA, Lightfoot WS, Jaffin R, Kumar A Implant placement with or without simultaneous tooth extraction in patients taking oral bisphosphonates: Postoperative healing, early follow-up, and the incidence of complications in two private practices. J Periodontol 2007;78:1664-9. |
| 30. | Goss A, Bartold M, Sambrook P, Hawker P The nature and frequency of bisphosphonate-associated osteonecrosis of the jaws in dental implant patients: A south australian case series. J Oral Maxillofac Surg 2010;68:337-43. |
| 31. | Memon S, Weltman RL, Katancik JA Oral bisphosphonates: Early endosseous dental implant success and crestal bone changes. A retrospective study. Int J Oral Maxillofac Implants 2012;27:1216-22. |
| 32. | Yajima N, Munakata M, Fuchigami K, Sanda M, Kasugai S Influence of bisphosphonates on implant failure rates and characteristics of postmenopausal woman mandibular jawbone. J Oral Implantol 2017;43:345-9. |
| 33. | Yip JK, Borrell LN, Cho SC, Francisco H, Tarnow DP Association between oral bisphosphonate use and dental implant failure among middle-aged women. J Clin Periodontol 2012;39:408-14. |
| 34. | Chadha GK, Ahmadieh A, Kumar S, Sedghizadeh P P Osseointegration of dental implants and osteonecrosis of the jaw in patients treated with bisphosphonate therapy: A systematic review. J Oral Implantol 2013;39:510-20. |
| 35. | Yarom N, Yahalom R, Shoshani Y, Hamed W, Regev E, Elad S Osteonecrosis of the jaw induced by orally administered bisphosphonates: Incidence, clinical features, predisposing factors and treatment outcome. Osteoporos Int 2007;18:1363-70. |
| 36. | Jacobsen C, Metzler P, Rössle M, Obwegeser J, Zemann W, Grätz KW Osteopathology induced by bisphosphonates and dental implants: Clinical observations. Clin Oral Investig 2013;17: 167-75. |
[Table 1]
|
Search Pubmed for