title: Strontium ranelate causes osteophytes overgrowth in a model of early phase osteoarthritis.
abstract: Osteoarthritis (OA) involves cartilage changes as well as modifications of subchondral bone and synovial tissues. Strontium ranelate (SR), an anti-osteoporosis compound, which is currently in phase III clinical trial for treatment of OA. Evidences suggest that SR preferably deposited in osteophyte, other than in subchondral bone in early phase of OA. This phenomenon raises concern about its utility for OA treatment as a disease-modifying drug. To evaluate the effect of SR on cartilage, subchondral bone mass and subchondral trabecular bone structure in medial meniscectomized (MNX) guinea pigs.
  
  
  
  Thirty-six 3-month-old male Dunkin Hartley albino guinea pigs received either sham or medial meniscectomy operations. One week after the procedure, meniscectomized animals began 12 weeks of SR (625 mg/kg, daily) treatment by oral gavage for MNX + SR group, or normal saline for MNX + V group. All animals were euthanized 12 weeks later, cartilage degeneration and subchondral bone micro-architecture was analyzed.
  
  
  
  Both OARSI scores (P = 0.523 for marcoscopic scores, P = 0.297 for histological scores) and Cartilage thickness (P = 0.335) in MNX + SR group were comparable to MNX + V group. However, osteophyte sizes were larger in MNX + SR group (P = 0.014), and collapsed osteophytes in MNX + SR group (7 by 12) were significantly more than in MNX + V group (1 by 12) (P = 0.027), while immunohistochemistry indicates catabolic changes in osteophyte/plateau junction. Micro-CT analysis showed bone mineral density (BMD) (P = 0.001), bone volume fraction (BV/TV) (P = 0.008), trabecular spacing (Tb.Sp) (P = 0.020), trabecular thickness (Tb.Th) (P = 0.012) and structure model index (SMI) (P = 0.005) levels to be significantly higher in the MNX + SR group than in the MNX + V group.
  
  
  
  SR (625 mg/kg/day) did not protect cartilage from degeneration in MNX guinea pigs but subchondral bone was significantly enhanced. In early phase OA, SR administration causes osteophyte overgrowth, which may be related to incorporation into mineralizing osteophytes. This adverse effect is important for future studies of SR in OA.
authors.affiliation: Department of Orthopedic Surgery, Hebei Medical University, Shijiazhuang, China.
authors.forename: Jian-Guo
authors.initials: JG
authors.lastname: Chu
authors.affiliation: Department of Orthopedic Surgery, Hebei Medical University, Shijiazhuang, China.
authors.forename: Mu-Wei
authors.initials: MW
authors.lastname: Dai
authors.affiliation: Department of Orthopedic Surgery, The Affiliated Hospital of North China University of Science and Technology, Tangshan, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Medical Research Center, North China University of Science and Technology, Tangshan, China.
authors.forename: Fa-Ming
authors.initials: FM
authors.lastname: Tian
authors.affiliation: Department of Orthopedic Surgery, The Affiliated Hospital of North China University of Science and Technology, Tangshan, China.
authors.forename: Hui-Ping
authors.initials: HP
authors.lastname: Song
authors.affiliation: Department of Orthopedic Surgery, The Affiliated Hospital of North China University of Science and Technology, Tangshan, China.
authors.forename: Ya-Ping
authors.initials: YP
authors.lastname: Xiao
authors.affiliation: Department of Orthopedic Surgery, The Affiliated Hospital of North China University of Science and Technology, Tangshan, China.
authors.forename: Li-Tao
authors.initials: LT
authors.lastname: Shao
authors.affiliation: Department of Orthopedic Surgery, Hebei Medical University, Shijiazhuang, China.
authors.forename: Ying-Ze
authors.initials: YZ
authors.lastname: Zhang
authors.affiliation: Department of Orthopedic Surgery, Hebei Medical University, Shijiazhuang, China. zhliu130@sohu.com.|Department of Orthopedic Surgery, The Affiliated Hospital of North China University of Science and Technology, Tangshan, China. zhliu130@sohu.com.
authors.forename: Liu
authors.identifier: 0000-0001-5239-3561
authors.initials: L
authors.lastname: Zhang
mesh_terms: D000818:Animals; D050071:Bone Density Conservation Agents / Q000627:therapeutic use / Q000633:toxicity*; D004195:Disease Models, Animal; D006168:Guinea Pigs; D008297:Male; D010003:Osteoarthritis / Q000188:drug therapy / Q000473:pathology*; D054850:Osteophyte / Q000139:chemically induced* / Q000473:pathology*; D013876:Thiophenes / Q000627:therapeutic use / Q000633:toxicity*
chemical_list: D050071:Bone Density Conservation Agents; D013876:Thiophenes; C081587:strontium ranelate
keywords: Cartilage; Micro-CT; Osteoarthritis; Osteophytes; Strontium ranelate; Subchondral bone