title: Local Administration of Bisphosphonate-soaked Hydroxyapatite for the Treatment of Osteonecrosis of the Femoral Head in Rabbit.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  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.
authors: Department of Bone and Joint Surgery, Peking University China Japan Friendship School of Clinical Medicine, Beijing 100029, China.
authors: Jin-Hui
authors: JH
authors: Ma
authors: 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.
authors: Wan-Shou
authors: WS
authors: Guo
authors: 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.
authors: Zi-Rong
authors: ZR
authors: Li
authors: 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.
authors: Bai-Liang
authors: BL
authors: Wang
mesh_terms: D000818:Animals; D004164:Diphosphonates / Q000008:administration & dosage / Q000627:therapeutic use*; D017886:Durapatite / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D005271:Femur Head Necrosis / Q000188:drug therapy* / Q000378:metabolism; D007093:Imidazoles / Q000008:administration & dosage / Q000627:therapeutic use; D007150:Immunohistochemistry; D008297:Male; D000077211:Zoledronic Acid
chemical_list: D004164:Diphosphonates; D007093:Imidazoles; D000077211:Zoledronic Acid; D017886:Durapatite