Department of Trauma and Reconstructive Surgery, Eberhard Karls University Tuebingen, BG Trauma Center Tuebingen, 72076, Tuebingen, Germany.
Institute for Clinical and Experimental Surgery, Saarland University, 66421, Homburg/Saar, Germany.
J Transl Med. 2023 Nov 23;21(1):844. doi: 10.1186/s12967-023-04661-y.
Non-union formation still represents a major burden in trauma and orthopedic surgery. Moreover, aged patients are at an increased risk for bone healing failure. Parathyroid hormone (PTH) has been shown to accelerate fracture healing in young adult animals. However, there is no information whether PTH also stimulates bone regeneration in atrophic non-unions in the aged. Therefore, the aim of the present study was to analyze the effect of PTH on bone regeneration in an atrophic non-union model in aged CD-1 mice.
After creation of a 1.8 mm segmental defect, mice femora were stabilized by pin-clip fixation. The animals were treated daily with either 200 mg/kg body weight PTH 1-34 (n = 17) or saline (control; n = 17) subcutaneously. Bone regeneration was analyzed by means of X-ray, biomechanics, micro-computed tomography (µCT) imaging as well as histological, immunohistochemical and Western blot analyses.
In PTH-treated animals bone formation was markedly improved when compared to controls. This was associated with an increased bending stiffness as well as a higher number of tartrate-resistant acid phosphatase (TRAP)-positive osteoclasts and CD31-positive microvessels within the callus tissue. Furthermore, PTH-treated aged animals showed a decreased inflammatory response, characterized by a lower number of MPO-positive granulocytes and CD68-positive macrophages within the bone defects when compared to controls. Additional Western blot analyses demonstrated a significantly higher expression of cyclooxygenase (COX)-2 and phosphoinositide 3-kinase (PI3K) in PTH-treated mice.
Taken together, these findings indicate that PTH is an effective pharmacological compound for the treatment of non-union formation in aged animals.
骨不连的形成仍然是创伤和骨科手术中的一个主要问题。此外，老年患者发生骨愈合失败的风险增加。甲状旁腺激素（PTH）已被证明可加速年轻成年动物的骨折愈合。然而，目前尚不清楚 PTH 是否也能刺激老年萎缩性骨不连中的骨再生。因此，本研究旨在分析 PTH 对 CD-1 老年小鼠萎缩性骨不连模型中骨再生的影响。
在创建 1.8mm 节段性缺损后，通过针夹固定稳定小鼠股骨。动物每天接受 200mg/kg 体重 PTH 1-34（n=17）或生理盐水（对照组；n=17）皮下治疗。通过 X 射线、生物力学、微计算机断层扫描（µCT）成像以及组织学、免疫组织化学和 Western blot 分析来分析骨再生。
与对照组相比，PTH 治疗的动物骨形成明显改善。这与骨痂组织中耐酒石酸酸性磷酸酶（TRAP）阳性破骨细胞和 CD31 阳性微血管数量增加有关。此外，与对照组相比，PTH 治疗的老年动物表现出炎症反应降低，特征为骨缺损内髓过氧化物酶（MPO）阳性粒细胞和 CD68 阳性巨噬细胞数量减少。此外，Western blot 分析表明 PTH 治疗的小鼠中环氧化酶（COX）-2 和磷酸肌醇 3-激酶（PI3K）的表达显著增加。
综上所述，这些发现表明 PTH 是治疗老年动物骨不连形成的有效药物化合物。
