Fujian Key Laboratory of Oral Diseases, School and Hospital of Stomatology, Fujian Medical University, Fujian, China.
Research Center of Dental and Craniofacial Implants, School and Hospital of Stomatology, Fujian Medical University, Fujian, China.
BMC Oral Health. 2024 Sep 27;24(1):1146. doi: 10.1186/s12903-024-04906-2.
Bisphosphonates (BPs) are widely used to inhibit excessive osteoclast activity. However, the potential to compromise bone defect healing has limited their broader application. To better understand the influence of BPs on bone regeneration, we established a bone grafting model with Zoledronate administration, aiming to deepen the understanding of bone remodeling and mineralization processes.
A bone grafting model was established in the distal femurs of male Sprague-Dawley rats. The experimental group received systemic administration of Zoledronate (ZOL, 0.2 mg/kg, administered twice). Histological analysis and immunohistochemistry (IHC) were employed to assess osteoblastic and macrophage activity, tartrate-resistant acid phosphatase (TRAP) staining was used to evaluate osteoclastogenesis. Mineralization was assessed through Micro-CT analysis, Raman spectroscopy, and back-scatter scanning electron microscopy (BSE-SEM). Additionally, the in vitro effects of ZOL on osteoblast and osteoclast activity were investigated to further elucidate its impact on bone regeneration.
In vivo, the ZOL group showed increased bone mass, as observed in histological and radiological assessments. However, Micro-CT, Raman spectroscopy, and BSE-SEM detection revealed lower mineralization levels in ZOL group's regenerated bone. Acid-etched SEM analysis showed abnormal osteocyte characteristics in ZOL-group's regenerated bone. Simultaneously, elevated osteopontin (OPN), F4/80 expression along with reduced TRAP expressing was found in the grafting region of ZOL group. In vitro, ZOL did not negatively impact osteogenetic activity (ALP, BMP4, OCN expression) at the tested concentrations (0.02-0.5 g/ml) but significantly impaired mineralization and inhibited osteoclast formation, even at the lowest concentration.
This study highlights a less recognized negative effect of ZOL on bone mineralization during bone regeneration. More research is needed to elucidate the underlying mechanism.
双膦酸盐（BPs）被广泛用于抑制破骨细胞的过度活动。然而，由于其可能影响骨缺损的愈合，限制了其更广泛的应用。为了更好地理解 BPs 对骨再生的影响，我们建立了一个用唑来膦酸给药的骨移植模型，旨在加深对骨重塑和矿化过程的理解。
在雄性 Sprague-Dawley 大鼠的股骨远端建立了一个骨移植模型。实验组接受唑来膦酸（ZOL，0.2mg/kg，两次给药）的全身给药。采用组织学分析和免疫组织化学（IHC）评估成骨细胞和巨噬细胞的活性，用抗酒石酸酸性磷酸酶（TRAP）染色评估破骨细胞的形成。通过 Micro-CT 分析、拉曼光谱和背散射扫描电子显微镜（BSE-SEM）评估矿化。此外，还研究了 ZOL 对成骨细胞和破骨细胞活性的体外影响，以进一步阐明其对骨再生的影响。
在体内，ZOL 组在组织学和影像学评估中显示出骨量增加。然而，Micro-CT、拉曼光谱和 BSE-SEM 检测显示 ZOL 组再生骨的矿化水平较低。酸蚀 SEM 分析显示 ZOL 组再生骨中的骨细胞特征异常。同时，在 ZOL 组的移植区域发现骨桥蛋白（OPN）、F4/80 表达增加，TRAP 表达减少。体外，在测试浓度（0.02-0.5g/ml）下，ZOL 对成骨活性（ALP、BMP4、OCN 表达）没有负面影响，但显著抑制矿化，并抑制破骨细胞的形成，即使在最低浓度下也是如此。
本研究强调了 ZOL 在骨再生过程中对骨矿化的一个较少被认识到的负面影响。需要进一步的研究来阐明潜在的机制。
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