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_Review_  
**Bisphosphonates and Their Influence on the Implant Failure: A Systematic Review**  
**[PERSON] 1, [PERSON] 2, [PERSON] 1, [PERSON] 1, and [PERSON] 1,3,*-**  
Footnote 1: Center for Interdisciplinary Research in Health (CIIS), Universidade Católica Portugues—Faculty of Dental Medicine (FMD-UCP), 3504-505 Visuei, Portugal  
Footnote 2: Private Practice, Ann Arbor, MI 48109, USA  
Footnote 3: Periodomics and Oral Medicine Department, University of Michigan School of Dentistry, Ann Arbor, MI 48109, USA  
Footnote 4: Correspondence: [EMAIL_ADDRESS]  
**Abstract: Objective: The goal of this systematic review was to study the relationship between the use of bisphosphonates (oral or intravenous) and its effect on implant osseointegration. Methods: The focused question was \"In patients medicated with bisphosphonates and who underwent surgery to place dental implants, what is the influence of that medication (of different generations) on the failure of dental implants (O)?\" Following specific eligibility criteria, four databases (PubMed/MEDLINE, Scopus, Web of Science, DOAJ) were electronically screened to search the articles. Specific MeSH terms were used in combinations with Boolean Operators \"AND\" and \"OR\" for the research. In addition, a manual search was done. The data extracted were the (i) author, (ii) year of publication, (iii) country, (iv) research question, (v) study design, (vi) patient information, (vii) the number of patients included, (viii) patient/implant status, (ix) the number of implants evaluated, (x) type of implant, (xi) risk factors, and (vii) findings obtained. Moreover, the following were also registered: the (i) type, generation, duration, and route for BP administrated; (ii) the presence of any systemic condition and drug treatment; (iii) follow-up (months); and (iv) implant failure rate (%). The quality assessment of the included studies was carried out using the Modified Newcastle-Ottawa scale. Results: A total of 491 articles were found (183 in PubMed/MEDLINE, 171 in Scopus, 65 in Web of Science, and 72 articles in DOAJ), and 17 articles were considered for full-text reading. After the exclusion of 3 articles, 14 were included in this systematic review (11 case reports, 2 retrospective, and 1 prospective study). The reasons for the bisphosphonates in intake included osteoporosis, multiple myeloma, breast cancer, knee cancer, and osteogenesis imperfets. The oral administration involved Alendronato (eight studies), Risedronate (three studies), and Ibandronate (three studies); whereas the intravenous administrations were Zoledronate (seven studies), Clodronate (one study), and Pamidronato (three studies). The duration of use of bisphosphonates at the time of implant placement was diverse; it ranged from no interruption of bisphosphonate intaking up to its discontinuation for 2, 3, or 6 months before surgery, with respective use being resumed 1, 3, or 8 months after surgery. Antibiotic treatment (amoxicillin + clavulamic acid) was performed before the intervention in two cases and after the intervention in three cases. Finally, the percent of implant failure rate when intaking BPs had an average of 49.96%. Conclusions: Within the limitation of this systematic review, it was possible to conclude that a high mean failure rate of implant osseointegration (49.96%) was found, regardless of the generation of bisphosphonates used. Moreover, the failure rate was lower in patients using second generation bisphosphonates (Alendronate and Pamidronate) and was higher with the IV administration compared to the oral administration of bisphosphonates.  
**Keywords:** bisphosphonates; dental implants; osseointegration; medication-related osteeonecrosis of the jaw