title: Bone microstructure and regional distribution of osteoblast and osteoclast activity in the osteonecrotic femoral head.
abstract: OBJECTIVE
  To detect and compare the bone microstructure and osteoblast and osteoclast activity in different regions of human osteonecrotic femoral heads.
  
  
  METHODS
  Osteonecrotic femoral heads were obtained from 10 patients (6 males, 4 females; Ficat IV) undergoing total hip arthroplasty between 2011 and 2013. The samples were divided into subchondral bone, necrotic, sclerotic, and healthy regions based on micro-computed tomography (CT) images. The bone microstructure, micromechanics, and osteoblast and osteoclast activity were assessed using micro-CT, pathology, immunohistochemistry, nanoindentation, reverse transcription polymerase chain reaction (RT-PCR), tartrate-resistant acid phosphatase staining and Western blotting.
  
  
  RESULTS
  (1) The spatial structure of the bone trabeculae differed markedly in the various regions of the osteonecrotic femoral heads. (2) The elastic modulus and hardness of the bone trabeculae in the healthy and necrotic regions did not differ significantly (P >0.05). (3) The subchondral bone and necrotic region were positive on TRAP staining, while the other regions were negative. (4) On immunohistochemical staining, RANK and RANKL staining intensities were increased significantly in the subchondral bone and necrotic region compared with the healthy region, while RUNX2 and BMP2 staining intensities were increased significantly in the sclerotic region compared with the necrotic region. (5) OPG, RANK, RANKL, RUNX2, BMP2, and BMP7 protein levels were greater in the necrotic and sclerotic region than in subchondral bone and the healthy region.
  
  
  CONCLUSIONS
  The micromechanical properties of bone trabeculae in the necrotic region did not differ significantly from the healthy region. During the progress of osteonecrosis, the bone structure changed markedly. Osteoclast activity increased in subchondral bone and the necrotic region while osteoblast activity increased in the sclerotic region. We speculate that the altered osteoblast and osteoclast activity leads to a reduction in macroscopic mechanical strength.
authors.affiliation: Institute of Orthopedics, Chinese PLA General Hospital, Haidian District, Beijing, P.R. China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Wang
authors.affiliation: Institute of Orthopedics, Chinese PLA General Hospital, Haidian District, Beijing, P.R. China.
authors.forename: Xin
authors.initials: X
authors.lastname: Wang
authors.affiliation: Institute of Orthopedics, Chinese PLA General Hospital, Haidian District, Beijing, P.R. China.
authors.forename: Xiao-long
authors.initials: XL
authors.lastname: Xu
authors.affiliation: Institute of Orthopedics, Chinese PLA General Hospital, Haidian District, Beijing, P.R. China.
authors.forename: Xue-ling
authors.initials: XL
authors.lastname: Yuan
authors.affiliation: Institute of Orthopedics, Chinese PLA General Hospital, Haidian District, Beijing, P.R. China.
authors.forename: Wen-long
authors.initials: WL
authors.lastname: Gou
authors.affiliation: Institute of Orthopedics, Chinese PLA General Hospital, Haidian District, Beijing, P.R. China.
authors.forename: Ai-yuan
authors.initials: AY
authors.lastname: Wang
authors.affiliation: Institute of Orthopedics, Chinese PLA General Hospital, Haidian District, Beijing, P.R. China.
authors.forename: Quan-yi
authors.initials: QY
authors.lastname: Guo
authors.affiliation: Institute of Orthopedics, Chinese PLA General Hospital, Haidian District, Beijing, P.R. China.
authors.forename: Jiang
authors.initials: J
authors.lastname: Peng
authors.affiliation: Institute of Orthopedics, Chinese PLA General Hospital, Haidian District, Beijing, P.R. China.
authors.forename: Shi-bi
authors.initials: SB
authors.lastname: Lu
mesh_terms: D019644:Arthroplasty, Replacement, Hip / Q000379:methods; D001842:Bone and Bones / Q000378:metabolism / Q000473:pathology* / Q000601:surgery; D055119:Elastic Modulus / Q000502:physiology; D005260:Female; D005270:Femur Head / Q000378:metabolism / Q000473:pathology* / Q000601:surgery; D005271:Femur Head Necrosis / Q000378:metabolism / Q000473:pathology* / Q000601:surgery; D006801:Humans; D008297:Male; D010006:Osteoblasts / Q000378:metabolism / Q000473:pathology*; D010010:Osteoclasts / Q000378:metabolism / Q000473:pathology*; D053245:RANK Ligand / Q000378:metabolism; D053246:Receptor Activator of Nuclear Factor-kappa B / Q000378:metabolism
chemical_list: D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; C505686:TNFRSF11A protein, human