Platelet-derived growth factor promotes periodontal regeneration in localized osseous defects: 36-month extension results from a randomized, controlled, double-masked clinical trial

Abstract

Background: Recombinant human platelet-derived growth factor (rhPDGF) is safe and effective for the treatment of periodontal defects in short-term studies up to 6 months in duration. We now provide results from a 36-month extension study of a multicenter, randomized, controlled clinical trial evaluating the effect and long-term stability of PDGF-BB treatment in patients with localized severe periodontal osseous defects.

Methods: A total of 135 participants were enrolled from six clinical centers for an extension trial. Eighty-three individuals completed the study at 36 months and were included in the analysis. The study investigated the local application of β-tricalcium phosphate scaffold matrix with or without two different dose levels of PDGF (0.3 or 1.0 mg/mL PDGF-BB) in patients possessing one localized periodontal osseous defect. Composite analysis for clinical and radiographic evidence of treatment success was defined as percentage of cases with clinical attachment level (CAL) ≥2.7 mm and linear bone growth (LBG) ≥1.1 mm.

Results: The participants exceeding this composite outcome benchmark in the 0.3 mg/mL rhPDGF-BB group went from 62.2% at 12 months, 75.9% at 24 months, to 87.0% at 36 months compared with 39.5%, 48.3%, and 53.8%, respectively, in the scaffold control group at these same time points (P <0.05). Although there were no significant increases in CAL and LBG at 36 months among all groups, there were continued increases in CAL gain, LBG, and percentage bone fill over time, suggesting overall stability of the regenerative response.

Conclusion: PDGF-BB in a synthetic scaffold matrix promotes long-term stable clinical and radiographic improvements as measured by composite outcomes for CAL gain and LBG for patients possessing localized periodontal defects ( ClinicalTrials.gov no. CT01530126).

Trial registration: ClinicalTrials.gov NCT01530126.

Figures

Figure 1

A) Study timeline of the extension investigation. Patients were randomized at baseline and followed up at 3, 6,12, 24, and 36months after surgery and device delivery. BD = bone depth; W= width; GR = gingival recession; Sx = surgery. B) Patient disposition Consolidated Standards of Reporting Trials (CONSORT) flow diagram of patients from initial entry and 6, 12, 24, and 36 months after therapy.

Figure 2

PDGF promotes periodontal bone repair. A patient with a localized bony defect as initially described in the original study cohort is shown. The baseline defect (A), the 1-year reentry (B), the baseline radiograph (C), the 3-year postoperative radiograph (D), and the 10-year postoperative radiograph (E) and clinical photograph (F), demonstrating periodontal repair and stability of the result.

Figure 3

PDGF promotes periodontal wound repair. A localized osseous defect (A) has PDGF-BB delivered to the defect in the scaffold matrix (B). Radiographs at baseline (C) and 3 years postoperative (D).

Figure 4

PDGF delivery promotes CAL gain, PDR, and bone gain. A) PDR over time among groups. B) CAL gain. C) %BF. D) LBG. n = 83 to 178 participants per group (for details, see Fig. 1B). Bars show mean ±SD. *P <0.001 for scaffold vs. 0.3 mg/mL rhPDGF-BB; †P = 0.019, ‡P <0.007, §P = 0.022, ||P = 0.021, ¶P = 0.008 for scaffold vs. 1.0 mg/mL rhPDGF-BB.

Figure 5

Composite outcome analysis of CAL and LBG shows 0.3mg/mL PDGF stimulates periodontal regeneration. A) The percentage of participants demonstrating CAL > 2.7 mm and LBG > 1.1 mm. B) Composite outcome of CAL and %BF. *P = 0.017 for scaffold vs. 0.3 mg/mL rhPDGF-BB; †P <0.03 for scaffold vs. 1.0 mg/mL PDGF-BB; ‡P = 0.015, §P = 0.006 for scaffold vs. 0.3 mg/mL PDGF-BB.

Figure 6

Effect of smoking (A and B) and defect type (C and D) on LBG (A and C) and %BF (B and D). Bars show mean±SD(for details, see Fig. 1B).*P <0.001 for scaffold vs. 0.3mg/mL rhPDGF-BB; †P <0.03for scaffold vs. 1.0 mg/mL PDGF-BB (data not shown).