Department of Periodontics and Oral Medicine, University of Michigan School of Dentistry, Ann Arbor, MI, 48109, USA.
Biointerfaces Institute, University of Michigan, Ann Arbor, MI, 48109-2800, USA.
Sci Rep. 2020 Oct 1;10(1):16217. doi: 10.1038/s41598-020-73026-y.
Destruction of the alveolar bone in the jaws can occur due to periodontitis, trauma or following tumor resection. Common reconstructive therapy can include the use of bone grafts with limited predictability and efficacy. Romosozumab, approved by the FDA in 2019, is a humanized sclerostin-neutralizing antibody (Scl-Ab) indicated in postmenopausal women with osteoporosis at high risk for fracture. Preclinical models show that Scl-Ab administration preserves bone volume during periodontal disease, repairs bone defects surrounding dental implants, and reverses alveolar bone loss following extraction socket remodeling. To date, there are no studies evaluating Scl-Ab to repair osseous defects around teeth or to identify the efficacy of locally-delivered Scl-Ab for targeted drug delivery. In this investigation, the use of systemically-delivered versus low dose locally-delivered Scl-Ab via poly(lactic-co-glycolic) acid (PLGA) microspheres (MSs) was compared at experimentally-created alveolar bone defects in rats. Systemic Scl-Ab administration improved bone regeneration and tended to increase cementogenesis measured by histology and microcomputed tomography, while Scl-Ab delivered by MSs did not result in enhancements in bone or cemental repair compared to MSs alone or control. In conclusion, systemic administration of Scl-Ab promotes bone and cemental regeneration while local, low dose delivery did not heal periodontal osseous defects in this study.
由于牙周炎、创伤或肿瘤切除后，颌骨的牙槽骨会遭到破坏。常见的重建疗法可能包括使用具有有限预测性和疗效的骨移植物。2019 年，FDA 批准了罗莫索单抗，这是一种人源化的硬骨素中和抗体（Scl-Ab），用于治疗有骨折高风险的绝经后骨质疏松症妇女。临床前模型表明，Scl-Ab 给药可在牙周病期间保留骨量，修复牙种植体周围的骨缺损，并在拔牙窝重塑后逆转牙槽骨丢失。迄今为止，尚无研究评估 Scl-Ab 修复牙齿周围的骨缺损，或确定局部给予 Scl-Ab 用于靶向药物输送的疗效。在这项研究中，通过聚（乳酸-共-乙醇酸）（PLGA）微球（MS）比较了全身给予 Scl-Ab 与低剂量局部给予 Scl-Ab 的效果，在大鼠实验性牙槽骨缺损中。全身给予 Scl-Ab 可改善骨再生，并倾向于通过组织学和微计算机断层扫描来增加牙骨质形成，而与单独给予 MS 或对照相比，MS 给予 Scl-Ab 并未导致骨或牙骨质修复增强。总之，本研究中，全身给予 Scl-Ab 可促进骨和牙骨质再生，而局部给予低剂量 Scl-Ab 则不能治愈牙周骨缺损。
