Platelet-derived growth factor stimulates bone fill and rate of attachment level gain: Results of a large multicenter randomized controlled trial
Platelet-derived growth factor stimulates bone fill and rate of attachment level gain: Results of a large multicenter randomized controlled trial
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DOI：
10.1902/jop.2005.76.12.2205
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发表时间：
2005-12-01
影响因子：
4.3
通讯作者：
Lynch, SE
中科院分区：
文献类型：
--
作者：
Nevins, M;Giannobile, WV;Lynch, SE
背景：生长因子被普遍认为是组织修复的重要介质，其作用机制包括刺激血管生成和细胞增殖、长入、分化和基质生物合成。本研究的目的是通过一项大规模、前瞻性、盲法和随机对照临床试验来评估纯化重组人血小板衍生生长因子（rhPDGF-BB）与合成β -磷酸三钙（β - tcp）基质混合治疗晚期牙周骨缺损愈合6个月的安全性和有效性。方法：11个临床中心纳入180名受试者，每位受试者均需要手术治疗4毫米或更大的骨内牙周缺损，并符合所有纳入和排除标准。受试者随机分为三个治疗组：1)β - tcp + 0.3 mg/ml rhPDGF-BB缓冲液；2) β - tcp + 1.0 mg/ml rhPDGF-BB缓冲液；3) beta-TCP +缓冲区（主动控制）。安全性数据通过不良事件的频率和严重程度进行评估。有效性测量包括临床附着水平（CAL）和牙龈退缩（GR），临床测量的线性骨生长（LBG）和骨填充百分比（% BF），由独立的集中放射学审查中心进行放射学评估。曲线下面积（AUC），一种对愈合速度的评估，也被计算用于CAL测量。外科医生、临床和放射学评估人员、患者和研究发起者都对治疗组进行了掩盖。结果：3个月时，与3组（β - tcp +缓冲液）相比，I组（rhPDGF 0.3 mg/ml）的CAL增益显著增加（3.8 vs 3.3 mm； P= 0.032），尽管到6个月时，这一发现无统计学意义（P= 0.11）。通过AUC评估，这种早期CAL增加的加速导致1组在基线和6个月之间的CAL增加率明显高于3组（68.4- vs 60.1 mm周；P= 0.033）。在6个月时，rhPDGF （0.3 mg/ml）处理的部位也比接受骨代用缓冲剂的部位具有更大的线性骨增益（分别为2.6和0.9 mm, P < 0.001）和百分比的缺损填充（分别为57%和18%，P < 0.001）。第1组3个月时的GR低于第3组（P= 0.04）；6个月时，组1的GR保持不变，而组3的牙龈高度略有增加，导致GR无可比拟。没有任何治疗导致的严重不良事件。结论：据我们所知，这项研究是迄今为止报道的最大的前瞻性、随机、三盲和对照关键临床试验，评估了假定的牙周再生和伤口愈合治疗。结果表明：rhPDGF-BB治疗牙周骨缺损安全有效。与β - tcp骨替代物相比，rhPDGF-BB治疗在术后3个月刺激了CAL增加率的显著增加，减少了牙龈萎缩，并在6个月改善了骨填充。
Background: Growth factors are generally accepted to be essential mediators of tissue repair via well-established mechanisms of action that include stimulatory effects on angiogenesis and cellullar proliferation, ingrowth, differentiation, and matrix biosynthesis. The aim of this study was to evaluate in a large-scale, prospective, blinded, and randomized controlled clinical trial the safety and effectiveness of purified recombinant human platelet-derived growth factor (rhPDGF-BB) mixed with a synthetic beta-tricalcium phosphate (beta-TCP) matrix for the treatment of advanced periodontal osseous defects at 6 months of healing.Methods: Eleven clinical centers enrolled 180 subjects, each requiring surgical treatment of a 4 mm or greater intrabony periodontal defect and meeting all inclusion and exclusion criteria. Subjects were randomized into one of three treatment groups: 1) beta-TCP + 0.3 mg/ml rhPDGF-BB in buffer; 2) beta-TCP + 1.0 mg/ml rhPDGF-BB in buffer; and 3) beta-TCP + buffer (active control). Safety data were assessed by the frequency and severity of adverse events. Effectiveness measurements included clinical attachment levels (CAL) and gingival recession (GR) measured clinically and linear bone growth (LBG) and percent bone fill (% BF) as assessed radiographically by an independent centralized radiology review center. The area under the curve (AUC), an assessment of the rate of healing, was also calculated for CAL measurements. The surgeons, clinical and radiographic evaluators, patients, and study sponsor were all masked with respect to treatment groups.Results: CAL gain was significantly greater at 3 months for group I (rhPDGF 0.3 mg/ml) compared to group 3 (beta-TCP+ buffer) (3.8 versus 3.3 mm; P= 0.032), although by 6 months, this finding was not statistically significant (P= 0.11). This early acceleration of CAL gain led to group 1 exhibiting a significantly greater rate of CAL gain between baseline and 6 months than group 3 as assessed by the AUC (68.4- versus 60.1-mm weeks; P= 0.033). rhPDGF (0.3 mg/ml)-treated sites also had significantly greater linearbone gain (2.6 versus 0.9 mm, respectively; P < 0.001) and percent defect fill (57%versus 18%, respectively; P < 0.001) than the sites receiving the bone substitute with buffer at 6 months. There was less GR at 3 months in group I compared to group 3 (P= 0.04); at 6 months, GR for group 1 remained unchanged, whereas there was a slight gain in gingival height for group 3 resulting incomparable GR. There were no serious adverse events attributable to any of the treatments.Conclusions: To our knowledge, this study is the largest prospective, randomized, triple-blinded, and controlled pivotal clinical trial reported to date assessing a putative periodontal regenerative and wound healing therapy. The study demonstrated that the use of rhPDGF-BB was safe and effective in the treatment of periodontal osseous defects. Treatment with rhPDGF-BB stimulated a significant increase in the rate of CAL gain, reduced gingival recession at 3 months post-surgery, and improved bone fill as compared to a beta-TCP bone substitute at 6 months.