Ma Jin-Hui, Guo Wan-Shou, Li Zi-Rong, Wang Bai-Liang
Department of Bone and Joint Surgery, Peking University China Japan Friendship School of Clinical Medicine, Beijing 100029, China.
Department of Bone and Joint Surgery, Peking University China Japan Friendship School of Clinical Medicine, Beijing 100029; Department of Bone and Joint Surgery, Center for Osteonecrosis and Joint Preserving and Reconstruction, China Japan Friendship Hospital, Beijing 100029, China.
Chin Med J (Engl). 2016 Nov 5;129(21):2559-2566. doi: 10.4103/0366-6999.192768.
Systemic administration of bisphosphonates has shown promising results in the treatment of osteonecrosis of the femoral head (ONFH). However, few studies have evaluated the efficacy of local zoledronate (ZOL) administration in the treatment of ONFH. The purpose of this study was to investigate whether local administration of bisphosphonate-soaked hydroxyapatite (HA) could improve bone healing in an experimental rabbit model of ONFH.
This experimental study was conducted between October 2014 and June 2015. Forty-five rabbits underwent simulated ONFH surgery. Immediately following surgery, they were divided into three groups: model (untreated, n = 15), HA (treated with HA alone, n = 15), and HA + ZOL (treated with HA soaked in a low-dose ZOL solution, n = 15). Histological, immunohistochemical, and quantitative analyses were performed to evaluate bone formation and resorption 2, 4, and 8 weeks after surgery.
Gross bone matrix and hematopoietic tissue formation were observed in the HA + ZOL group 4 weeks after surgery. The immunohistochemical staining intensities for 5-bromodeoxyuridine, runt-related transcription factor 2, osteocalcin, osteopontin, and osteoprotegerin were significantly higher in the HA + ZOL group than that in the model (P < 0.001, P< 0.001, P< 0.001, P< 0.001, and P = 0.018, respectively) and HA groups (P = 0.003, P = 0.049, P< 0.001, P = 0.020, and P = 0.019, respectively), whereas receptor activator of the nuclear factor-κB ligand staining intensity was significantly lower in the HA + ZOL group than that in the model and HA groups (P = 0.029 and P = 0.015, respectively) 4 weeks after surgery. No significant differences in bone formation or bone resorption marker expression were found between the three groups 2 or 8 weeks after surgery (P > 0.05).
Local administration of HA soaked in a low-dose ZOL solution increased new bone formation while inhibiting bone resorption in an animal model of ONFH, which might provide new evidence for joint-preserving surgery in the treatment of ONFH.
双膦酸盐的全身给药在股骨头坏死（ONFH）治疗中已显示出有前景的结果。然而，很少有研究评估局部使用唑来膦酸（ZOL）治疗ONFH的疗效。本研究的目的是调查局部给予双膦酸盐浸泡的羟基磷灰石（HA）是否能改善ONFH实验兔模型中的骨愈合。
本实验研究于2014年10月至2015年6月进行。45只兔子接受了模拟ONFH手术。手术后立即将它们分为三组：模型组（未治疗，n = 15）、HA组（仅用HA治疗，n = 15）和HA + ZOL组（用低剂量ZOL溶液浸泡的HA治疗，n = 15）。在术后2、4和8周进行组织学、免疫组织化学和定量分析，以评估骨形成和骨吸收情况。
术后4周在HA + ZOL组观察到粗大的骨基质和造血组织形成。HA + ZOL组中5-溴脱氧尿苷、 runt相关转录因子2、骨钙素、骨桥蛋白和骨保护素的免疫组织化学染色强度显著高于模型组（分别为P < 0.001、P < 0.001、P < 0.001、P < 0.001和P = 0.018）和HA组（分别为P = 0.003、P = 0.049、P < 0.001、P = 0.020和P = 0.019），而术后4周HA + ZOL组中核因子κB受体激活剂配体染色强度显著低于模型组和HA组（分别为P = 0.029和P = 0.015）。术后2周或8周，三组之间在骨形成或骨吸收标志物表达方面未发现显著差异（P > 0.05）。
局部给予低剂量ZOL溶液浸泡的HA在ONFH动物模型中增加了新骨形成，同时抑制了骨吸收，这可能为ONFH的保关节手术提供新的证据。
