Effect of anatomical location (mandible vs maxilla) of dental implants on the BMP-2, BMP-7, sRANKL and OPG levels in periimplant crevicular fluid during osseointegration. A pilot study

Abstract

Background:The aim of this study was to investigate levels of bone morphogenetic protein-2 (BMP-2), BMP-7, soluble receptor activator of nuclear factor-kB ligand (sRANKL) and osteoprotegerin (OPG) in the peri-implant crevicular fluid (PICF) of  implants placed in both maxilla and mandible during the osseointegration period.

Methods:Thirty-three patients (17 females and 16 males; mean age 47.03±11.23 years) were included in this study. A total of 33 implants were placed in both of maxilla (Group 1/n=18) and mandible (group 2/n=15). Peri-implant crevicular fluid (PICF) samples, modified plaque index (MPI), gingival index (GI) and probing depth (PD) measurements were obtained at 1 and 3 months after surgery. PICF levels of BMP-2/-7, sRANKL and OPG were analyzed by ELISA.

Results:No complications were observed during the healing period. No significant differences were observed in the PICF levels of sRANKL, OPG, BMP-2 and BMP-7 and evaluated clinical parameters between groups at any time point (p>0.05). While PICF volume of group 2 was greater than group 1 at first month, PICF volume of group 1 was greater than group 2 at 3 months (p<0.05). There was a positive correlation between sRANKL levels and PICF volume (p<0.05) and a strong correlation between BMP-2 and BMP-7 (p<0.01).

Conclusions:The results of this pilot study didn’t show any significant difference in PICF levels of BMP-2, BMP-7, sRANKL, and OPG in terms of anatomic location of dental implants. Further well-designed studies should be carried out to evaluate the relationship between bone related biomarkers and anatomic location of dental implants.

Keywords

• Bone morphogenetic proteins
• dental implant
• osteoprotegerin
• receptor activator of nuclear factor-kappa B

Dental implantların anatomik lokasyonlarının (mandibula ile maxilla) osseointegrasyon süresince peri-implant oluğu sıvısındaki BMP-2, BMP-7, sRANKL ve OPG seviyeleri üzerine herhangi bir etkisi yoktur. Pilot bir çalışma

Abstract

Amaç: Bu çalışmanın amacı, hem maksilla hemde mandibulaya yerleştirilen implantların periimplant oluğu sıvısında osseointegrasyon süresi boyunca kemik morfogenetik protein-2 (BMP-2), BMP-7, çözünür reseptör aktivatör nükleer faktör kappa B ligandı (sRANKL)  ve osteoprotegrin (OPG) seviyelerinin araştırılmasıdır.

Gereç ve Yöntemler:Bu çalışmada 33 hasta (17 bayan ve 16 erkek; ortalama yaş 47.03±11.23) yer almıştır. Hem maxillaya (Grup 1/n=18) hemde mandibulaya (Grup 2/n=15) olmak üzere toplam 33 implant yerleştirilmiştir. Peri-implant oluğu sıvısı (PIS) örnekleri, modifiye plak indeksi (MPI), gingival indeks (GI) ve sondlama cep derinliği (SCD) ölçümleri cerrahiden sonra 1. ve 3. ayda alındı. BMP-2/-7, sRANKL ve OPG PIS seviyeleri ELIZA ile incelendi.

Bulgular:İyileşme süresince herhangi bir komplikasyon gözlenmedi.Gruplar arasında sRANKL, OPG, BMP-2 ve BMP-7 PIS seviyeleri ve incelenen klinik parametreler açısından herhangi bir zaman periyodunda anlamlı fark gözlenmedi (p>0.05). PIS hacmi 1. ayda grup 2 de grup 1’e göre fazla iken, 3. ayda PIS hacmi grup 1 de grup 2’ye göre fazlaydı (p<0.05). PIS hacmi ile sRANKL arasında pozitif (p<0.05) ve BMP-2 ile BMP-7 arasında güçlü pozitif korelasyon (p<0.01) mevcuttu. 

Sonuçlar:Bu pilot çalışmanın sonuçları, dental implantların anatomik lokasyonları açısından BMP-2, BMP-7, sRANKL, ve OPG PIS seviyelerinde anlamlı bir fark gösterememiştir. Kemik ile ilişkili biyobelirteçler ve dental implantların anatomic lokasyonu arasındaki ilişkinin değerlendirilmesi için iyi dizayn edilmiş çalışmalar yapılmalıdır.

Keywords

• Kemik morfogenetik proteinleri
• dental implant
• osteoprotegrin
• reseptör aktivatör nükleer kappa B ligand

References

1. 1. Mavrogenis AF, Dimitriou R, Parvizi J, Babis GC. Biology of implant osseointegration. J Musculoskelet Neuronal Interact 2009;9:61-71.
2. 2. Fini M, Giavaresi G, Torricelli P, et al. Osteoporosis and biomaterial osteointegration. Biomed Pharmacother 2004;58:487-493.
3. 3. Davies JE. Mechanisms of endosseous integration. Int J Prosthodont 1998;11:391-401.
4. 4. Kalfas IH. Principles of bone healing. Neurosurg Focus 2001;10:E1.
5. 5. Kugimiya F, Kawaguchi H, Kamekura S, et al. Involvement of endogenous bone morphogenetic protein (BMP) 2 and BMP6 in bone formation. J Biol Chem 2005;280:35704-35712.
6. 6. Garrison KR, Shemilt I, Donell S, et al. Bone morphogenetic protein (BMP) for fracture healing in adults. Cochrane Database Syst Rev 2010:CD006950.
7. 7. Yilgor P, Tuzlakoglu K, Reis RL, Hasirci N, Hasirci V. Incorporation of a sequential BMP-2/BMP-7 delivery system into chitosan-based scaffolds for bone tissue engineering. Biomaterials 2009;30:3551-3559.
8. 8. Bessa PC, Casal M, Reis RL. Bone morphogenetic proteins in tissue engineering: the road from laboratory to clinic, part II (BMP delivery). J Tissue Eng Regen Med 2008;2:81-96.

9. 9. Chen D, Zhao M, Mundy GR. Bone morphogenetic proteins. Growth Factors 2004;22:233-241.
10. 10. Belibasakis GN, Bostanci N. The RANKL-OPG system in clinical periodontology. J Clin Periodontol 2012;39:239-248.
11. 11. Yasuda H, Shima N, Nakagawa N, et al. Osteoclast differentiation factor is a ligand for osteoprotegerin/osteoclastogenesis-inhibitory factor and is identical to TRANCE/RANKL. Proc Natl Acad Sci U S A 1998;95:3597-3602.
12. 12. Suda T, Takahashi N, Udagawa N, Jimi E, Gillespie MT, Martin TJ. Modulation of osteoclast differentiation and function by the new members of the tumor necrosis factor receptor and ligand families. Endocr Rev 1999;20:345-357.
13. 13. Hughes FJ, Turner W, Belibasakis G, Martuscelli G. Effects of growth factors and cytokines on osteoblast differentiation. Periodontol 2000 2006;41:48-72.14. Lekholm O, Zarb, G.A. Patient selection and preparation. In: In:Branemark PI et al Editors: Tissue integrated prostheses - Osseointegration in clinical dentistry. Chicago: Quintessence, 1985:199-209.
14. 15. Elias CN. Factors Affecting the Success of Dental Implants. In: Turkyilmaz I, ed. Implant Dentistry - A Rapidly Evolving Practice: InTech, 2011:342.
15. 16. Gulsahi A. Bone Quality Assessment for Dental Implants. In: Turkyilmaz I, ed. Implant Dentistry - The Most Promising Discipline of Dentistry: InTech, 2011:444-445.
16. 17. Dolanmaz D, Saglam M, Inan O, Dundar N, Alniacık G, Gursoy Trak B, Kocak E, Hakki SS. Monitoring bone morphogenetic protein-2 and -7, soluble receptor activator of nuclear factor-kB ligand and osteoprotegerin levels in the peri-implant sulcular fluid during the osseointegration of hydrophilic-modified sandblasted acid-etched and sandblasted acid-etched surface dental implants. J Periodontal Res 2015; 50: 62–73
17. 18. Mombelli A, van Oosten MA, Schurch E, Jr., Land NP. The microbiota associated with successful or failing osseointegrated titanium implants. Oral Microbiol Immunol 1987;2:145-151.
18. 19. Loe H. The Gingival Index, the Plaque Index and the Retention Index Systems. J Periodontol 1967;38:Suppl:610-616.
19. 20. Griffiths GS. Formation, collection and significance of gingival crevice fluid. Periodontol 2000 2003;31:32-42.
20. 21. Tolstunov L. Implant zones of the jaws: implant location and related success rate. J Oral Implantol 2007;33:211-220.
21. 22. Davies JE. Understanding peri-implant endosseous healing. J Dent Educ 2003;67:932-949.
22. 23. Misch C. Bone density: A Key Determinant for Treatment Planning. In: Misch C, Abbas, H.A., ed. Contemporary Implant Dentistry. vol. Third edition. Canada Elsevier:135-140.
23. 24. Lamster IB, Oshrain RL, Gordon JM. Enzyme activity in human gingival crevicular fluid: considerations in data reporting based on analysis of individual crevicular sites. J Clin Periodontol 1986;13:799-804.
24. 25. Nakashima K, Roehrich N, Cimasoni G. Osteocalcin, prostaglandin E2 and alkaline phosphatase in gingival crevicular fluid: their relations to periodontal status. J Clin Periodontol 1994;21:327-333.
25. 26. Bi W, Gu Z, Zheng Y, Zhang X, Guo J, Wu G. Heterodimeric BMP-2/7 antagonizes the inhibition of all-trans retinoic acid and promotes the osteoblastogenesis. PLoS One 2013;8:e78198.
26. 27. Vlacic-Zischke J, Hamlet SM, Friis T, Tonetti MS, Ivanovski S. The influence of surface microroughness and hydrophilicity of titanium on the up-regulation of TGFbeta/BMP signalling in osteoblasts. Biomaterials 2011;32:665-671.
27. 28. Mamalis AA, Markopoulou C, Vrotsos I, Koutsilirieris M. Chemical modification of an implant surface increases osteogenesis and simultaneously reduces osteoclastogenesis: an in vitro study. Clin Oral Implants Res 2011;22:619-626.
28. 29. Eriksson C, Nygren H, Ohlson K. Implantation of hydrophilic and hydrophobic titanium discs in rat tibia: cellular reactions on the surfaces during the first 3 weeks in bone. Biomaterials 2004;25:4759-4766.
29. 30. Takebe J, Ito S, Champagne CM, Cooper LF, Ishibashi K. Anodic oxidation and hydrothermal treatment of commercially pure titanium surfaces increases expression of bone morphogenetic protein-2 in the adherent macrophage cell line J774A.1. J Biomed Mater Res A 2007;80:711-718.
30. 31. Boyce BF, Xing L. Biology of RANK, RANKL, and osteoprotegerin. Arthritis Res Ther 2007;9 Suppl 1:S1.
31. 32. Nagasawa T, Kiji M, Yashiro R, et al. Roles of receptor activator of nuclear factor-kappaB ligand (RANKL) and osteoprotegerin in periodontal health and disease. Periodontol 2000 2007;43:65-84.
32. 33. Boyce BF, Xing L. Functions of RANKL/RANK/OPG in bone modeling and remodeling. Arch Biochem Biophys 2008;473:139-146.
33. 34. Bartold PM, Cantley MD, Haynes DR. Mechanisms and control of pathologic bone loss in periodontitis. Periodontol 2000 2010;53:55-69.
34. 35. Monov G, Strbac GD, Baron M, Kandler B, Watzek G, Gruber R. Soluble RANKL in crevicular fluid of dental implants: a pilot study. Clin Implant Dent Relat Res 2006;8:135-141.
35. 36. Arikan F, Buduneli N, Kutukculer N. Osteoprotegerin levels in peri-implant crevicular fluid. Clin Oral Implants Res 2008;19:283-288.
36. 37. Sarlati F, Sattari M, Gazar AG, Rafsenjani AN. Receptor activator of nuclear factor kappa B ligand (RANKL) levels in peri-implant crevicular fluid. Iran J Immunol 2010;7:226-233.
37. 38. Bostanci N, Ilgenli T, Emingil G, et al. Gingival crevicular fluid levels of RANKL and OPG in periodontal diseases: implications of their relative ratio. J Clin Periodontol 2007;34:370-376.
38. 39. Guncu GN, Akman AC, Gunday S, Yamalik N, Berker E. Effect of inflammation on cytokine levels and bone remodelling markers in peri-implant sulcus fluid: a preliminary report. Cytokine 2012;59:313-316.
39. 40. Rausch-fan X, Qu Z, Wieland M, Matejka M, Schedle A. Differentiation and cytokine synthesis of human alveolar osteoblasts compared to osteoblast-like cells (MG63) in response to titanium surfaces. Dent Mater 2008;24:102-110.
40. 41. Hall J, Britse AO, Jemt T, Friberg B. A controlled clinical exploratory study on genetic markers for peri-implantitis. Eur J Oral Implantol 2011;4:371-382.42. Pontoriero R, Tonelli MP, Carnevale G, Mombelli A, Nyman SR, Lang NP. Experimentally induced peri-implant mucositis. A clinical study in humans. Clin Oral Implants Res 1994;5:254-259.
41. 43. Lekholm U, Ericsson I, Adell R, Slots J. The condition of the soft tissues at tooth and fixture abutments supporting fixed bridges. A microbiological and histological study. J Clin Periodontol 1986;13:558-562.
42. 44. Quirynen M, van Steenberghe D, Jacobs R, Schotte A, Darius P. The reliability of pocket probing around screw-type implants. Clin Oral Implants Res 1991;2:186-192.
43. 45. Bengazi F, Wennstrom JL, Lekholm U. Recession of the soft tissue margin at oral implants. A 2-year longitudinal prospective study. Clin Oral Implants Res 1996;7:303-310.
44. 46. Weber HP, Crohin CC, Fiorellini JP. A 5-year prospective clinical and radiographic study of non-submerged dental implants. Clin Oral Implants Res 2000;11:144-153.
45. 47. Behneke A, Behneke N, d'Hoedt B, Wagner W. Hard and soft tissue reactions to ITI screw implants: 3-year longitudinal results of a prospective study. Int J Oral Maxillofac Implants 1997;12:749-757.
46. 48. Salvi GE, Lang NP. Diagnostic parameters for monitoring peri-implant conditions. Int J Oral Maxillofac Implants 2004;19 Suppl:116-127.
47. 49. Schenk RK, Buser D. Osseointegration: a reality. Periodontol 2000 1998;17:22-35.
48. 50. Ioannidou E, Doufexi A. Does loading time affect implant survival? A meta-analysis of 1,266 implants. J Periodontol 2005;76:1252-1258.