A Novel Approach to Treating Retrograde Peri-Implantitis

Periapical lesions or radiolucencies around implants pose a unique challenge to the dental team. Retrograde peri-implantitis (RPI) is defined as a clinically symptomatic periapical lesion that develops after implant placement and maintains normal bone-to-implant contact at the coronal aspect.^1,2 The prevalence of RPI is generally very low. A retrospective study of 1,651 implants over 20 years noted a prevalence of RPI of 0.34%.³

While there is no consensus about the etiology of RPI, several factors have been proposed, including bacterial contamination of the implant surface and surgical site, thermal osteonecrosis, over-extension of the implant bed, pre-existing bone diseases, presence of foreign bodies or root fragments, and endodontic complications of adjacent teeth.^4-6

The diagnosis of RPI is made both clinically and radiographically. Reiser and Nevins⁷ first classified these lesions as either inactive (not infected) or active (infected). Inactive lesions present without clinical signs and symptoms. They often decrease in size and are usually attributed to an over-extension of the implant osteotomy. Active lesions, however, increase in size and are associated with swelling, pain, erythema, and/or fistula formation.⁷

There is no singular treatment for RPI, as it largely depends on its clinical and radiographic presentation.⁸ Inactive lesions are usually monitored with radiographs, assuming they do not expand. Although proper self-care and regular maintenance are critical to implant success, they do not directly affect the incidence of RPI because its pathogenesis is related to the implant apex.

Active lesions require surgical intervention to prevent further osseous breakdown and to mitigate patient symptoms. This can include implant removal and replacement, implant flap debridement, or regenerative therapy using a bone graft, membrane, and/or growth factor. Some protocols also include resection of the implant apex for complete disinfection.⁸

The use of growth factors has revolutionized oral regeneration around teeth and implants. These natural biological mediators regulate crucial cellular events involved in tissue repair and even enhance the development of lamellar bone in the craniofacial complex.⁹ One of the best-documented growth factors is recombinant human platelet-derived growth factor (rh-PDGF) and it is derived from human platelet cells following tissue injury.¹⁰ Obtained with recombinant DNA processing, rh-PDGF upregulates angiogenesis and promotes guided bone regeneration in large horizontal ridge defects. Its main effect is mitogenesis and chemotaxis for cells of mesenchymal origin, increasing the potential for regeneration.^10,11 In 2005, the United States Food and Drug Administration approved purified rh-PDGF with an osteoconductive matrix, tricalcium phosphate (β-TCP).

A recent systematic review that assessed the clinical efficacy, benefits, and safety of rh-PDGF in hard and soft tissue regeneration reported that the combined use of bone graft substitutes, namely xenografts and allografts, successfully achieved root coverage, ridge augmentation, and/or ridge preservation.¹¹ Bone substitutes act as an osteoconductive, three-dimensional matrix, or scaffold enhanced by the chemotactic, mitogenic, and angiogenic properties of rh-PDGF, leading to improved wound healing, osteogenesis, and defect resolution.¹¹

Case Report

An 81-year-old man presented to a private practice for implant placement (Figures 1 to 11). He had a medical history of type 2 diabetes mellitus (T2DM), cardiovascular disease, and osteoarthritis. He reported taking metformin, canagliflozin, and amlodipine/benazepril to manage these conditions and an allergy to penicillin. His T2DM was well-controlled with regular monitoring of his blood glucose levels and a self-reported HbA1c of 5.2%.

The patient first presented for extraction and bone grafting of nonrestorable #30 due to a failing root canal. Tooth #30 was extracted in a minimally traumatic fashion. The socket was thoroughly curetted to remove granulation tissue, and an allograft was condensed into the socket. A noncross-linked collagen membrane was prepared and placed under the buccal and the lingual flap margins and stabilized with resorbable sutures.

Ridge healing was uneventful. Four months later, after cone-beam computed tomography (CBCT) imaging was obtained, a bone-level, 6 mm-wide and 11.5 mm-long implant was placed at site #30. The patient was referred to his general dentist for implant crown delivery after 5 months of healing.

Nine months after crown insertion, the patient returned for implant evaluation. He complained of swelling and tenderness to percussion and palpation. Clinical examination revealed > 6 mm pocketing between #30/31 with bleeding on probing and suppuration and a draining buccal fistula. Tooth #31 tested normal to vitality testing with no lingering pain nor tenderness to percussion. A size 40 gutta percha master cone was used to trace the fistula to the apical region of the implant. The patient was placed on clindamycin 150 mg and metronidazole 500 mg three times daily for 1 week following American Dental Association guidelines for periapical pain.¹²

After a thorough evaluation and review of different treatment options, a surgical plan was developed. Due to the radiograph indicating a clearly defined lesion and the use of gutta percha to locate the source of the abscess, an additional CBCT was not deemed necessary. The patient consented to implant flap debridement with guided bone regeneration or implant removal and bone grafting for future implant replacement.

The patient premedicated with 300 mg of clindamycin 1 hour prior to surgery to minimize complications in early healing.¹³ Full-thickness flaps were elevated to allow for complete visualization of the intrabony defects. After degranulation with titanium scalers, the two-wall defect measured 9-mm deep between #30/31 and the three-wall defect at #30-M were amendable to grafting. The implant surface was rinsed with 0.12% chlorhexidine and sterile saline. Tetracycline (50 mg/ml) was used to detoxify the implant surface for 2 to 3 minutes followed by another saline rinse. rh-PDGF was then applied to the root and implant surfaces, while a bone allograft was hydrated with this growth factor for approximately 20 minutes before being condensed into the defect. A noncrosslinked collagen membrane was layered over the grafted site. Flaps were repositioned with long-lasting, synthetic, resorbable sutures. The patient was prescribed clindamycin 300 mg and anti-inflammatory and analgesic agents during the perioperative period.

After several weeks of healing, the tissues surrounding #29-31 were healthy, pink, and firm. The patient was scheduled for monthly visits to monitor healing and reinforce proper oral hygiene with interproximal aids. Probing depths from #29-31 were < 4 mm at time of the final follow-up. He was referred back to his general dentist and maintained every 4 to 6 months.

Discussion

The majority of RPI occur between 1 week and 4 years after implant placement with an increased prevalence for prior or adjacent endodontic complications.^2,4 The treated RPI was diagnosed within that timeline. Residual bacteria may have been encapsulated in the bone even after debridement of the extraction socket and reactivated during implant bed preparation with subsequent colonization of the implant apex.¹⁴

Treatment was initiated with a course of antibiotics to address the active infection, localized swelling, and reduce the bacterial load prior to surgery. Despite its indications, the use of clindamycin is conflicting due to its adverse gastrointestinal effects and potential for significantly increased implant failure in penicillin-allergic patients.¹⁶

The decision to maintain the implant rested on the implant stability and defect anatomy. Regenerative flap therapy has been recommended for cases with peri-implant bone loss less than 50% and lack of implant mobility.¹⁵ In this case, despite the severe intrabony defect associated with the mesial root of the molar, extending to and including the apex of the implant, the lack of clinical mobility of the tooth and implant favored retention and subsequent periodontal regeneration. The patient was informed that the implant could still require removal and replacement over time.

A key step in the management of RPI is effective biofilm removal. A variety of strategies have been used for implant surface decontamination.¹⁷ Titanium scalers, rotary nylon brushes, and air polishing with glycine and erythritol powders have proven effective in eliminating calculus deposits and residual debris; however, undercuts, grooves, and porosities along roughened implant surfaces make it impossible to achieve a totally aseptic environment and introduce the potential for titanium dissolution into the surrounding tissues and microbial dysbiosis during instrumentation.^18,19

Laser decontamination yielded positive results in animal models but its clinical use remains controversial with no true superiority to the aforementioned instruments in biofilm removal.²⁰ Some chemotherapeutic agents, such as chlorhexidine, have more recently been shown to negatively alter the physicochemistry and cytocompatibility of titanium implants via the osteoblastic response, despite their long history as adjuncts intra- and post-operatively.²¹ At this time, there is no one mechanical or pharmacological agent that is superior in managing peri-implant lesions.¹⁹

Burnishing the implant surface with cotton pellets soaked in sterile saline has been reported to significantly reduce the level of pathogenic lipopolysaccharides and remove the peri-implant biofilm.¹⁹ Sterile saline is also cost effective with no cytotoxic effects to human osteoblasts.²²

Tetracycline was used to further reduce the bacterial load along the implant body. Case reports in humans have shown that 50 mg/ml of tetracycline applied for 5 minutes after implantoplasty and followed by an autogenous bone graft or xenograft and membrane arrested disease progression and promoted radiographic bone fill of peri-implant defects.^7,19 There is no definitive treatment for RPI and the evidence for most materials beyond sterile saline is conflicting.^8,22 With this in mind, implant debridement with saline alone would have been sufficient for biofilm removal based on human and animal studies and should be considered in future applications of this protocol.^19,21,22

To the best of our knowledge, this is the first case report using rh-PDGF with an allograft material in the treatment of RPI. After 4 months, radiographs indicated adequate healing with marginal bone stability. The patient also had probing depths ≤ 4 mm with no bleeding on probing or suppuration. Studies have consistently found that true periodontal regeneration of cementum, periodontal ligament, and bone can be achieved using rh-PDGF with allograft, xenograft, and, to a lesser extent, β-TCP.^23,24

In all cases, there was either a statistical improvement in bone regeneration or a strong trend toward bone gain in rh-PDGF-treated sites.²³ Most recently, a case study reported the benefits of rh-PDGF on bone grafting procedures for severe ridge deficiencies in concomitance with periodontal attachment loss.²⁴ In this case report, the bone replacement allograft was used as a scaffold and carrier for the rh-PDGF in a combined periodontal and peri-implant defect. The blend of cortical and cancellous bone particles in the allograft gives this product the structure of cortical chips, with the open scaffolding for bone to grow into offered by cancellous chips. The lack of osteogenic properties of these bone graft materials was overcome by the use of rh-PDGF.

Conclusion

This case report provides evidence for the potential use of rh-PDGF in challenging peri-implant defects; however, the treatment protocol described is not a standard clinical guideline. The use of chemotherapeutic agents in biofilm removal around implants is controversial.^18,19,21 Further studies should be performed to validate these findings as they pertain to the surgical treatment of RPI.

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References

1. Quirynen M, Gijbels F, Jacobs R. An infected jawbone site compromising successful osseointegration. Periodontol 2000. 2003;33:129-144.
2. Wiedemann TG. A clinical approach to treatment of retrograde peri-implantitis. Compend Contin Educ Dent. 2021;42:170-175.
3. Di Murro B, Canullo L, Pompa G, Di Murro C, Papi P. Prevalence and treatment of retrograde peri-implantitis: A retrospective cohort study covering a 20-year period. Clin Oral Investig. 2021;25:4553-4561.
4. Zhou W, Han C, Li D, Li Y, Song Y, Zhao Y. Endodontic treatment of teeth induces retrograde peri-implantitis. Clin Oral Implants Res. 2009;20:1326-1332.
5. Temmerman A, Lefever D, Teughels W, Balshi TJ, Balshi SF, Quirynen M. Etiology and treatment of periapical lesions around dental implants. Periodontol 2000. 2014;66:247-254.
6. Penarrocha-Oltra D, Blaya-Tarraga JA, Menendez-Nieto I, Penarrocha-Diago M, Penarrocha-Diago M. Factors associated with early apical peri-implantitis: A retrospective study covering a 20-year period. Int J Oral Implantol (Berl). 2020;13:65-73.
7. Reiser GM, Nevins M. The implant periapical lesion: etiology, prevention, and treatment. Compend Contin Educ Dent. 1995;16:768–772.
8. Burdurlu MC, Dagasan VC, Tunc O, Guler N. Retrograde peri-implantitis: evaluation and treatment protocols of a rare lesion. Quintessence Int. 2021;52:112-121.
9. Donos N, Dereka X, Calciolari E. The use of bioactive factors to enhance bone regeneration: A narrative review. J Clin Periodontol. 2019;46 Suppl 21:124-161.
10. Yao W, Shah B, Chan HL, Wang HL, Lin GH. Bone quality and quantity alterations after socket augmentation with rhpdgf-bb or bmps: a systematic review. Int J Oral Maxillofac Implants. 2018;33:1255-1265.
11. Tavelli L, Ravida A, Barootchi S, Chambrone L, Giannobile WV. Recombinant human platelet-derived growth factor: a systematic review of clinical findings in oral regenerative procedures. JDR Clin Trans Res. 2021;6:161-173.
12. Lockhart P, Tampi M, Abt E, et al. Evidence-based clinical practice guideline on antibiotic use for the urgent management of pulpal- and periapical-related dental pain and intraoral swelling: A report from the American Dental Association. J Am Dent Assoc. 2019;150:906-921.
13. Arrieta G, Sanchez F, Rodriguez-Audres C, Barbier L, Arteagoitia, I. The effect of preoperative clindamycin in reducing early oral implant failure: a randomized placebo-controlled clinical trial. Cl Oral Invest. 2023;27:1113-1122.
14. Marshall G, Canullo L, Logan RM, Rossi-Fedele G. Histopathological and microbiological findings associated with retrograde peri-implantitis of extra-radicular endodontic origin: a systematic and critical review. Int J Oral Maxillofac Surg. 2019;48:1475-1484.
15. Sarmast ND, Wang HH, Sajadi AS, Munne AM, Angelov N. Nonsurgical endodontic treatment of necrotic teeth resolved apical lesions on adjacent implants with retrograde/apical peri-implantitis: a case series with 2-year follow-up. J Endod. 2019;45:645-650.
16. Zahra B, Nicholas B, Geoffrey R, Dina Z, Janal MN, Stuart F. Dental implant failure rates in patients with self-reported allergy to penicillin. Clin Implant Dent Relat Res. 2022;24:301-306.
17. Francis S, Iaculli F, Perrotti V, Piattelli A, Quaranta A. Titanium surface decontamination: a systematic review of in vitro comparative studies. Int J Oral Maxillofac Implants. 2022;37:76-84
18. Kotsakis GA, Black R, Kum J, et al. Effect of implant cleaning on titanium particle dissolution and cytocompatibility. J Periodontol. 2021;92:580-591.
19. Monje A, Amerio E, Cha JK, et al. Strategies for implant surface decontamination in peri-implantitis therapy. Int J Oral Implantol (Berl). 2022;15:213-248.
20. Patil S, Bhandi S, Alzahrani KJ, et al. Efficacy of laser in re-osseointegration of dental implants-a systematic review. Lasers Med Sci. 2023;38:199.
21. Kotsakis GA, Lan C, Barbosa J, et al. Antimicrobial agents used in the treatment of peri-implantitis alter the physicochemistry and cytocompatibility of titanium surfaces. J Periodontol. 2016;87:809-819.
22. Brunello G, Becker K, Scotti L, Drescher D, Becker J, John G. The effects of three chlorhexidine-based mouthwashes on human osteoblast-like saos-2 cells. An in vitro study. Int J Mol Sci. 2021;22:9986.
23. Meghil MM, Mandil O, Nevins M, Saleh MHA, Wang HL. Histologic evidence of oral and periodontal regeneration using recombinant human platelet-derived growth factor. Medicina (Kaunas). 2023;59:676.
24. Urban IA, Tattan M, Ravida A, Saleh MH, Tavelli L, Avila-Ortiz G. Simultaneous alveolar ridge augmentation and periodontal regenerative therapy leveraging recombinant human platelet-derived growth factor-bb (rhpdgf-bb): a case report. Int J Periodontics Restorative Dent. 2022;42:577-585.

From Decisions in Dentistry. April/May 2024; 10(3):36,39-41