title: Systemic application of teriparatide for steroid induced osteonecrosis in a rat model.
abstract: BACKGROUND
  Steroid associated osteonecrosis is difficult to treat. Teriparatide, as the only one bone anabolic drug, has achieved very promising effect in osteoporosis and other bone skeletal diseases. We carried out this animal study to evaluate the effect of subcutaneous injection of teriparatide for the steroid induced femoral head necrosis in a rat model.
  
  
  METHODS
  24 Sprague-Dawley male adult rats were included in the study. All the rats were randomized into 4 groups: 18 rats from LPS/MPS group, LPS/MPS + PTH group and LPS/MPS + NS group were given lipopolysaccharide (20 μg/kg) and methylprednisolone (40 mg/kg) to establish the steroid induced osteonecrosis model. 6 rats from NS group only received normal saline. 4 weeks later, All the rats in LPS/MPS group and NS group were sacrificed and the femoral heads were harvested. After that, the 6 rats in the LPS/MPS + PTH group received subcutaneous injection of 20 μg/kg teriparatide and LPS/MPS + NS group only received equal amount of normal saline. After 4 weeks, the serum bone marker was tested and the femoral head were harvested. Micro-CT and histological examination were performed to compare the incidence of osteonecrosis and trabeculae parameters for the femoral head.
  
  
  RESULTS
  At 4 weeks, rats in LPS/MPS group showed significant osteonecrosis by histological examination (83.3 %) which suggested successful steroid induced osteronecrosis animal models were established. After the treatment of 4 weeks, the LPS/MPS + PTH group showed significant lower incidence rate of osteonecrosis compared with the LPS/MPS + NS group (16.7 % vs.75 %, P < 0.05). The micro CT examination showed higher bone volume/total volume, trabecula thickness and bone mineral density in the LPS/MPS + PTH group compared with the LPS/MPS + NS group. The serum osteocalcin was a little higher in the LPS/MPS + PTH group (4.54 ± 1.61vs.3.58 ± 1.81, P = 0.358), but it didn't reach a statistical significance.
  
  
  CONCLUSIONS
  Systemic application of teriparatide for steroid induced osteonecrosis in rats showed a beneficial effect. This may be one promising therapy for early stage osteonecrosis.
authors.affiliation: Deparment of Orthopaedic Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, 100730, Beijing, China. yuleidong@126.com.
authors.forename: Yulei
authors.initials: Y
authors.lastname: Dong
authors.affiliation: Deparment of Orthopaedic Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, 100730, Beijing, China. 15010599823@126.com.
authors.forename: Yulong
authors.initials: Y
authors.lastname: Li
authors.affiliation: Deparment of Orthopaedic Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, 100730, Beijing, China. 823939234@qq.com.
authors.forename: Cheng
authors.initials: C
authors.lastname: Huang
authors.affiliation: Institute of laboratory animal sciences, Chinese Academy of Medical Science and Peking Union Medical College, 100021, Beijing, China. 390289952@qq.com.
authors.forename: Kai
authors.initials: K
authors.lastname: Gao
authors.affiliation: Deparment of Orthopaedic Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, 100730, Beijing, China. xshweng@medmail.com.cn.
authors.forename: Xisheng
authors.initials: X
authors.lastname: Weng
mesh_terms: D000818:Animals; D001706:Biopsy; D050071:Bone Density Conservation Agents / Q000008:administration & dosage*; D004195:Disease Models, Animal; D005270:Femur Head / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000473:pathology; D005271:Femur Head Necrosis / Q000139:chemically induced / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology; D007279:Injections, Subcutaneous; D008070:Lipopolysaccharides; D008297:Male; D008775:Methylprednisolone; D017207:Rats, Sprague-Dawley; D019379:Teriparatide / Q000008:administration & dosage*; D013997:Time Factors; D055114:X-Ray Microtomography
chemical_list: D050071:Bone Density Conservation Agents; D008070:Lipopolysaccharides; C482199:lipopolysaccharide, E coli O55-B5; D019379:Teriparatide; D008775:Methylprednisolone