The effects of intro-oral parathyroid hormone on the healing of tooth extraction socket: an experimental study on hyperglycemic rats

Abstract Objective To investigate the effects of intro-oral injection of parathyroid hormone (PTH) on tooth extraction wound healing in hyperglycemic rats. Methodology 60 male Sprague-Dawley rats were randomly divided into the normal group (n=30) and DM group (n=30). Type 1 diabetes mellitus (DM) was induced by streptozotocin. After extracting the left first molar of all rats, each group was further divided into 3 subgroups (n=10 per subgroup), receiving the administration of intermittent PTH, continuous PTH and saline (control), respectively. The intermittent-PTH group received intra-oral injection of PTH three times per week for two weeks. A thermosensitive controlled-release hydrogel was synthesized for continuous-PTH administration. The serum chemistry was determined to evaluate the systemic condition. All animals were sacrificed after 14 days. Micro-computed tomography (Micro-CT) and histological analyses were used to evaluate the healing of extraction sockets. Results The level of serum glucose in the DM groups was significantly higher than that in the non-DM groups (p<0.05); the level of serum calcium was similar in all groups (p>0.05). Micro-CT analysis showed that the DM group had a significantly lower alveolar bone trabecular number (Tb.N) and higher trabecular separation (Tb.Sp) than the normal group (p<0.05). The histological analyses showed that no significant difference in the amount of new bone (hard tissue) formation was found between the PTH and non-PTH groups (p>0.05). Conclusions Bone formation in the extraction socket of the type 1 diabetic rats was reduced. PTH did not improve the healing of hard and soft tissues. The different PTH administration regimes (continuous vs. intermittent) had similar effect on tissue healing. These results demonstrated that the metabolic characteristics of the hyperglycemic rats produced a condition that was unable to respond to PTH treatment.

摘要
目的：探讨经口内注射甲状旁腺激素（parathyroid hormone, PTH）对高血糖大鼠拔牙创愈合的影响。
方法：将60只雄性斯普拉格-道利（Sprague-Dawley）大鼠随机分为正常组（n=30）与糖尿病组（n=30），采用链脲佐菌素（streptozotocin）诱导1型糖尿病（Type 1 diabetes mellitus, DM）模型。所有大鼠拔除左侧第一磨牙后，每组再分为3个亚组（每组n=10），分别接受间歇性PTH、持续性PTH及生理盐水（对照）干预。间歇性PTH组每周经口内注射PTH 3次，持续2周；为实现持续性PTH给药，本研究合成了温敏控释水凝胶。通过血清生化检测评估大鼠全身代谢状态，于干预后14天处死所有动物，采用显微计算机断层扫描（Micro-computed tomography, Micro-CT）及组织学分析评估拔牙窝愈合情况。
结果：糖尿病组血糖水平显著高于非糖尿病组（p<0.05）；各组血清钙水平无显著差异（p>0.05）。显微计算机断层扫描分析显示，糖尿病组牙槽骨骨小梁数目（trabecular number, Tb.N）显著低于正常组，骨小梁分离度（trabecular separation, Tb.Sp）显著高于正常组（p<0.05）。组织学分析结果表明，PTH干预组与非干预组的新生骨（硬组织）生成量无显著差异（p>0.05）。
结论：1型糖尿病大鼠拔牙窝内骨生成能力受损；PTH未能改善其软硬组织愈合效果；两种PTH给药方案（持续性与间歇性）对组织愈合的影响无显著差异。本研究结果证实，高血糖大鼠的代谢特征使其无法对PTH治疗产生应答。