Hong Christine, Quach Alison, Lin Lawrence, Olson Jeffrey, Kwon Taewoo, Bezouglaia Olga, Tran Jaime, Hoang Michael, Bui Kimberly, Kim Reuben H, Tetradis Sotirios
Section of Orthodontics, Division of Growth and Development, UCLA School of Dentistry, Los Angeles, California, United States of America.
UCLA School of Dentistry, Los Angeles, California, United States of America.
PLoS One. 2018 Jan 5;13(1):e0190901. doi: 10.1371/journal.pone.0190901. eCollection 2018.
A majority of patients with orofacial cleft deformity requires cleft repair through a bone graft. However, elevated amount of bone resorption and subsequent bone graft failure remains a significant clinical challenge. Bisphosphonates (BPs), a class of anti-resorptive drugs, may offer great promise in enhancing the clinical success of bone grafting. In this study, we compared the effects of systemic and local delivery of BPs in an intraoral bone graft model in rats. We randomly divided 34 female 20-week-old Fischer F344 Inbred rats into four groups to repair an intraoral critical-sized defect (CSD): (1) Control: CSD without graft (n = 4); (2) Graft/Saline: bone graft with systemic administration of saline 1 week post-operatively (n = 10); (3) Graft/Systemic: bone graft with systemic administration of zoledronic acid 1 week post-operatively (n = 10); and (4) Graft/Local: bone graft pre-treated with zoledronic acid (n = 10). At 6-weeks post-operatively, microCT volumetric analysis showed a significant increase in bone fraction volume (BV/TV) in the Graft/Systemic (62.99 ±14.31%) and Graft/Local (69.35 ±13.18%) groups compared to the Graft/Saline (39.18±10.18%). Similarly, histological analysis demonstrated a significant increase in bone volume in the Graft/Systemic (78.76 ±18.00%) and Graft/Local (89.95 ±4.93%) groups compared to the Graft/Saline (19.74±18.89%). The local delivery approach resulted in the clinical success of bone grafts, with reduced graft resorption and enhanced osteogenesis and bony integration with defect margins while avoiding the effects of BPs on peripheral osteoclastic function. In addition, local delivery of BPs may be superior to systemic delivery with its ease of procedure as it involves simple soaking of bone graft materials in BP solution prior to graft placement into the defect. This new approach may provide convenient and promising clinical applications towards effectively managing cleft patients.
大多数患有口面部裂畸形的患者需要通过骨移植进行腭裂修复。然而，骨吸收量升高以及随后的骨移植失败仍然是一个重大的临床挑战。双膦酸盐（BPs）是一类抗吸收药物，在提高骨移植的临床成功率方面可能具有很大的前景。在本研究中，我们比较了在大鼠口腔内骨移植模型中全身和局部递送BPs的效果。我们将34只20周龄的雌性Fischer F344近交系大鼠随机分为四组，以修复口腔内临界大小缺损（CSD）：（1）对照组：无移植的CSD（n = 4）；（2）移植/生理盐水组：术后1周全身给予生理盐水的骨移植（n = 10）；（3）移植/全身组：术后1周全身给予唑来膦酸的骨移植（n = 10）；（4）移植/局部组：用唑来膦酸预处理的骨移植（n = 10）。术后6周，显微CT体积分析显示，与移植/生理盐水组（39.18±10.18%）相比，移植/全身组（62.99±14.31%）和移植/局部组（69.35±13.18%）的骨体积分数（BV/TV）显著增加。同样，组织学分析表明，与移植/生理盐水组（19.74±18.89%）相比，移植/全身组（78.76±18.00%）和移植/局部组（89.95±4.93%）的骨体积显著增加。局部递送方法导致了骨移植的临床成功，减少了移植吸收，增强了成骨作用以及与缺损边缘的骨整合，同时避免了BPs对外周破骨细胞功能的影响。此外，BPs的局部递送可能优于全身递送，因为其操作简便，只需在将骨移植材料植入缺损之前将其简单浸泡在BP溶液中即可。这种新方法可能为有效治疗腭裂患者提供方便且有前景的临床应用。
