title: A prospective, randomized pilot study on the safety and efficacy of recombinant human growth and differentiation factor-5 coated onto β-tricalcium phosphate for sinus lift augmentation.
abstract: OBJECTIVE
  The aim of this prospective, randomized clinical trial was to investigate the potential of recombinant human growth and differentiation factor-5 (rhGDF-5) coated onto β-tricalcium phosphate (β-TCP) (rhGDF-5/β-TCP) to support bone formation after sinus lift augmentation.
  
  
  METHODS
  In total, 31 patients participated in this multicenter clinical trial. They required a two-stage unilateral maxillary sinus floor augmentation (residual bone height <5 mm). According to a parallel-group design, the patients were randomized to three treatment groups: (a) augmentation with rhGDF-5/β-TCP and a 3-month healing period, (b) augmentation with rhGDF-5/β-TCP and a 4-month healing period and (c) medical device β-TCP mixed with autologous bone and a 4-month healing period. The primary study objective was the area of newly formed bone within the augmented area as assessed by histomorphometric evaluation of trephine bur biopsies.
  
  
  RESULTS
  The osseous regeneration was similar in each treatment group; the amount of newly formed bone ranged between 28% (± 15.5%) and 31.8% (± 17.9%). Detailed analysis of histological data will be published elsewhere. As secondary efficacy variables, the augmentation height at the surgery site was measured by radiography. The largest augmentation was radiologically achieved in the rhGDF-5/β-TCP - 3-month and the rhGDF-5/β-TCP - 4-month treatment groups. As safety parameters, adverse events were recorded and anti-drug antibody levels were evaluated. Most of the adverse events were judged as unrelated to the study medication. Four out of 47 (8.5%) implants failed in patients treated with rhGDF-5/β-TCP, a result that is in agreement with the general implant failure rate of 5-15%. Transiently very low amounts of anti-rhGDF-5 antibodies were detected in some patients who received rhGDF-5, which was not related to the bone formation outcome.
  
  
  CONCLUSIONS
  rhGDF-5/β-TCP was found to be effective and safe as the control treatment with autologous bone mixed β-TCP in sinus floor augmentation. Thus, further investigation regarding efficacy and safety will be carried out in larger patient populations.
authors.affiliation: Department of Oral and Maxillofacial Surgery, University Medical Centre of the Johannes Gutenberg University Mainz, Mainz, Germany. koch@mkg.klinik.uni-mainz.de
authors.forename: Felix P
authors.initials: FP
authors.lastname: Koch
authors.forename: Jürgen
authors.initials: J
authors.lastname: Becker
authors.forename: Hendrik
authors.initials: H
authors.lastname: Terheyden
authors.forename: Björn
authors.initials: B
authors.lastname: Capsius
authors.forename: Wilfried
authors.initials: W
authors.lastname: Wagner
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000540:Alveolar Ridge Augmentation / Q000379:methods*; D015519:Bone Density / Q000187:drug effects; D001861:Bone Regeneration / Q000187:drug effects; D016025:Bone Transplantation / Q000379:methods*; D002130:Calcium Phosphates / Q000494:pharmacology*; D020099:Coated Materials, Biocompatible / Q000737:chemistry; D005260:Female; D055428:Growth Differentiation Factor 5 / Q000494:pharmacology*; D006801:Humans; D008297:Male; D008443:Maxillary Sinus / Q000601:surgery*; D008875:Middle Aged; D010865:Pilot Projects; D011446:Prospective Studies; D023822:Tissue Engineering; D014182:Transplantation, Autologous; D016896:Treatment Outcome
chemical_list: D002130:Calcium Phosphates; D020099:Coated Materials, Biocompatible; C525893:GDF5 protein, human; D055428:Growth Differentiation Factor 5; C485817:beta-tricalcium phosphate