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A phase IIa randomized controlled pilot study evaluating the safety and clinical outcomes following the use of rhGDF-5/β-TCP in regenerative periodontal therapy

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Abstract

To present the safety profile, the early healing phase and the clinical outcomes at 24 weeks following treatment of human intrabony defects with open flap debridement (OFD) alone or with OFD and rhGDF-5 adsorbed onto a particulate β-tricalcium phosphate (β-TCP) carrier. Twenty chronic periodontitis patients, each with at least one tooth exhibiting a probing depth ≥6 mm and an associated intrabony defect ≥4 mm entered the study. Ten subjects (one defect/patient) were randomized to receive OFD alone (control) and ten subjects OFD combined with rhGDF-5/β-TCP. Blood samples were collected at screening, and at weeks 2 and 24 to evaluate routine hematology and clinical chemistry, rhGDF-5 plasma levels, and antirhGDF-5 antibody formation. Plaque and gingival indices, bleeding on probing, probing depth, clinical attachment level, and radiographs were recorded pre- and 24 weeks postsurgery. Comparable safety profiles were found in the two treatment groups. Neither antirhGDF-5 antibody formation nor relevant rhGDF-5 plasma levels were detected in any patient. At 6 months, treatment with OFD + rhGDF-5/β-TCP resulted in higher but statistically not significant PD reduction (3.7 ± 1.2 vs. 3.1 ± 1.8 mm; p = 0.26) and CAL gain (3.2 ± 1.7 vs. 1.7 ± 2.2 mm; p = 0.14) compared to OFD alone. In the tested concentration, the use of rhGDF-5/β-TCP appeared to be safe and the material possesses a sound biological rationale. Thus, further adequately powered, randomized controlled clinical trials are warranted to confirm the clinical relevance of this new approach in regenerative periodontal therapy. rhGDF-5/β-TCP may represent a promising new techology in regenerative periodontal therapy.

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References

  1. Caton JG (2000) Greenstein GG (1993) Factors related to periodontal regeneration. Periodontol 1:9–15

    Article  Google Scholar 

  2. Wikesjö UME (2000) Selvig KA (1999) Periodontal wound healing and regeneration. Periodontol 19:21–39

    Article  Google Scholar 

  3. Polimeni G, Xiropaidis AV (2000) Wikesjö UME (2006) Biology and principles of periodontal wound healing/regeneration. Periodontol 41:30–47

    Article  Google Scholar 

  4. World Workshop in Periodontology (1996) The American Academy of Periodontology. Ann Periodontol 1:618–670

    Article  Google Scholar 

  5. Morotome Y, Goseki-Sone M, Ishikawa I, Oida S (1998) Gene expression of growth and differentiation factors-5, -6, and -7 in developing bovine tooth at the root forming stage. Biochem Biophys Res Commun 244:85–90

    Article  PubMed  Google Scholar 

  6. Sena K, Morotome Y, Baba O, Terashima T, Takano Y, Ishikawa I (2003) Gene expression of growth differentiation factors in the developing periodontium of rat molars. J Dent Res 82:166–171

    Article  PubMed  Google Scholar 

  7. Spiro RC, Liu L, Heidaran MA, Thompson AY, Ng CK, Pohl J, Poser JW (2000) Inductive activity of recombinant human growth and differentiation factor-5. Biochem Soc Trans 28:362–368

    Article  PubMed  Google Scholar 

  8. Nakamura T, Yamamoto M, Tamura M, Izumi Y (2003) Effects of growth/differentiation factor-5 on human periodontal ligament cells. J Periodont Res 38:597–605

    Article  PubMed  Google Scholar 

  9. Wikesjö UME, Sorensen RG, Kinoshita A, Li XJ, Wozney JM (2004) Periodontal repair in dogs: effect of recombinant human bone morphogenetic protein-12 (rhBMP-12) on regeneration of alveolar bone and periodontal attachment. A pilot study. J Clin Periodontol 31:622–670

    Article  Google Scholar 

  10. Kim TG, Wikesjö UME, Cho KS, Chai JK, Pippig SD, Siedler M, Kim CK (2009) Periodontal wound healing/regeneration following application of recombinant human growth/differentiation factor-5 (rhGDF-5) in an absorbable collagen sponge carrier into one-wall intrabony defects in dogs. A dose range study. J Clin Periodontol 36:589–597

    Article  PubMed  Google Scholar 

  11. Lee JS, Wikesjö UME, Jung UW, Choi SH, Pippig S, Siedler M, Kim CK (2010) Periodontal wound healing/regeneration following implantation of recombinant human growth/differentiation factor-5 in a beta-tricalcium phosphate carrier into one-wall intrabony defects in dogs. J Clin Periodontol 37:382–389

    Article  PubMed  Google Scholar 

  12. Galois L, Mainard D, DeLagoutte JP (2002) Beta-tricalcium phosphate ceramic as a bone substitute in orthopaedic surgery. Int Orthop 26:109–115

    Article  PubMed  Google Scholar 

  13. Pöhling S, Pippig SD, Hellerbrand K, Siedler M, Schütz A, Dony C (2006) Superior effect of MD05, beta-tricalcium phosphate coated with recombinant human growth/differentiation factor-5, compared to conventional bone substitutes in the rat calvarial defect model. J Periodontol 77:1582–1590

    Article  Google Scholar 

  14. Moore Y, Dickinson DP, Wikesjö UME (2010) Growth/differentiation factor-5 (GDF-5): a candidate therapeutic agent for periodontal regeneration? Review of preclinical data. J Clin Periodontol 37:288–298

    Article  PubMed  Google Scholar 

  15. Stavropoulos A, Windisch P, Gera I, Sculean A, Capsius B, Wikesjö UME (2011) A phase IIa randomized controlled clinical and histological pilot study evaluating rhGDF-5/β-TCP for periodontal regeneration. J Clin Periodontol (accepted for publication)

  16. O’Leary TJ, Drake RB, Naylor JE (1972) The plaque control record. J Clin Periodontol 43:38

    Article  Google Scholar 

  17. Ainamo J, Bay I (1975) Problems and proposals for recording gingivitis and plaque. Int Dent J 25:229–235

    PubMed  Google Scholar 

  18. Pöhling S, Jochims K, Happersberger P, Hellerbrand K, Bolz W, Kohnert U (2002) Enhancement of bone growth by coating of osteoinductive beta-tricalcium phosphate (beta- TCP) with recombinant human growth factor-5 (rhGDF-5). 2nd European Conference on Bone Morphogenetic Proteins, May 2002, Zagreb.

  19. Kwon DH, Bennett W, Herberg S, Bastone P, Pippig S, Rodriguez NA, Susin C, Wikesjö UME (2010) Evaluation of an injectable rhGDF-5/PLGA composite for minimally invasive periodontal regenerative procedures: a histological study in the dog. J Clin Periodontol 37:390–397

    Article  PubMed  Google Scholar 

  20. Nevins M, Giannobile WV, McGuire MK, Kao RT, Mellonig JT, Hinrinchs JE, McAllister BS, Murphy KS, McClain PK, Nevins ML, Paquette DW, Han TJ, Reddy MS, Lavin PT, Genco RJ, Lynch SE (2005) Platelet-derived growth factor stimulates bone fill and rate of attachment level gain: results of a large multicenter randomized controlled trial. J Periodontol 76:2205–2215

    Article  PubMed  Google Scholar 

  21. Pontoriero R, Wennström J, Lindhe J (1999) The use of barrier membranes and enamel matrix proteins in the treatment of angular bone defects. A prospective controlled clinical study. J Clin Periodontol 26:833–840

    Article  PubMed  Google Scholar 

  22. Sculean A, Windisch P, Chiantella GC, Donos N, Brecx M, Reich E (2001) Treatment of intrabony defects with enamel matrix proteins and guided tissue regeneration. A prospective controlled clinical study. J Clin Periodontol 28:397–403

    Article  PubMed  Google Scholar 

  23. Tonetti MS, Lang NP, Cortellini P, Suvan JE, Adriaens P, Dubravec D, Fonzar A, Fourmousis I, Mayfield L, Rossi R, Silvestri M, Tiedemann C, Topoll H, Vangsted T, Wallkamm B (2002) Enamel matrix proteins in the regenerative therapy of deep intrabony defects. A multicentre randomized controlled clinical trial. J Clin Periodontol 29:317–325

    Article  PubMed  Google Scholar 

  24. Kuru B, Yilmaz S, Argin K, Noyan U (2006) Enamel matrix derivative alone or in combination with a bioactive glass in wide intrabony defects. Clin Oral Invest 10:227–234

    Article  Google Scholar 

  25. Yilmaz S, Cakar G, Yildirim B, Sculean A (2010) Healing of two and three wall intrabony periodontal defects following treatment with an enamel matrix derivative combined with autoneous bone. J Clin Periodontol 37:544–550

    Article  PubMed  Google Scholar 

  26. Sculean A, Berakdar M, Chiantella GC, Donos N, Arweiler NB, Brecx M (2003) Healing of intrabony defects following treatment with a bovine derived xenograft and collagen membrane. A controlled clinical study. J Clin Periodontol 30:73–80

    Article  PubMed  Google Scholar 

  27. Tonetti MS, Cortellini P, Lang NP, Suvan JE, Adriaens P, Dubravec D, Fonzar A, Fourmousis I, Rasperini G, Rossi R, Silvestri M, Topoll H, Wallkamm B, Zybutz M (2004) Clinical outcomes following treatment of human intrabony defects with GTR/bone replacement material or access flap alone. A multicenter randomized controlled clinical trial. J Clin Periodontol 31:770–776

    Article  PubMed  Google Scholar 

  28. Rosling B, Nyman S, Lindhe J (1976) The effect oy systemic plaque control on bone regeneration in infrabony pockets. J Clin Periodontol 3:38–53

    Article  PubMed  Google Scholar 

  29. Stavropoulos A, Windisch P, Szendröi-Kiss D, Rosta P, Gera I, Sculean A (2010) Clinical and histological evaluation of granular beta tricalcium phosphate for the treatment of human intrabony periodontal defects: a report on five cases. J Periodontol 81:325–334

    Article  PubMed  Google Scholar 

  30. LeGeros RZ (1993) Biodegradation and bioresorption of calcium phosphate ceramics. Clin Mater 14:65–88

    Article  PubMed  Google Scholar 

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Sources of funding

This study was supported by a grant from Scil Technology GmbH, Martinsried, Germany.

Conflict of interest statement

Dr. Capsius is an employee of Scil Technology GmbH, Martinsried, Germany. Dr. Wikesjö is a consultant to Scil Technology GmbH. Drs. Sculean and Stavropulos received a grant from Scil Technology GmbH to conduct this study. Drs. Windisch, Molnár, Szendröi-Kiss, Szilágyi, Rosta, and Horváth report no finacial or other conflicting relationship to any products involved in this study.

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Authors and Affiliations

  1. Department of Periodontology, Semmelweis University, Budapest, Hungary

    Péter Windisch, Bálint Molnár, Dóra Szendröi-Kiss, Emese Szilágyi, Péter Rosta & Attila Horváth

  2. Department of Periodontology, School of Dentistry, University of Aarhus, Aarhus, Denmark

    Andreas Stavropoulos

  3. Center for Experimental and Preclinical Research (CEPBR), Athens, Greece

    Andreas Stavropoulos

  4. Scil Technology GmbH, Martinsried, Germany

    Björn Capsius

  5. Laboratory for Applied Periodontal & Craniofacial Regeneration (LAPCR), Departments of Periodontics and Oral Biology, Medical College of Georgia School of Dentistry and School of Graduate Studies, Augusta, GA, USA

    Ulf M. E. Wikesjö

  6. Department of Periodontology, University of Bern, Freiburgstrasse 7, 3010, Bern, Switzerland

    Anton Sculean

Authors
  1. Péter Windisch
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  2. Andreas Stavropoulos
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  3. Bálint Molnár
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  4. Dóra Szendröi-Kiss
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  5. Emese Szilágyi
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  6. Péter Rosta
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  7. Attila Horváth
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  8. Björn Capsius
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  9. Ulf M. E. Wikesjö
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  10. Anton Sculean
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Correspondence to Anton Sculean.

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Windisch, P., Stavropoulos, A., Molnár, B. et al. A phase IIa randomized controlled pilot study evaluating the safety and clinical outcomes following the use of rhGDF-5/β-TCP in regenerative periodontal therapy. Clin Oral Invest 16, 1181–1189 (2012). https://doi.org/10.1007/s00784-011-0610-3

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  • DOI: https://doi.org/10.1007/s00784-011-0610-3

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