Strontium ranelate causes osteophytes overgrowth in a model of early phase osteoarthritis

BMC Musculoskeletal Disorders

Research Article

Mu-Wei Dai¹  Jian-Guo Chu¹  Ying-Ze Zhang¹  Liu Zhang²  Li-Tao Shao³  Ya-Ping Xiao³  Hui-Ping Song³  Yu Wang³  Fa-Ming Tian⁴ 

[1] Department of Orthopedic Surgery, Hebei Medical University, Shijiazhuang, China;Department of Orthopedic Surgery, Hebei Medical University, Shijiazhuang, China;Department of Orthopedic Surgery, The Affiliated Hospital of North China University of Science and Technology, Tangshan, China;Department of Orthopedic Surgery, The Affiliated Hospital of North China University of Science and Technology, Tangshan, China;Medical Research Center, North China University of Science and Technology, Tangshan, China;

关键词: Osteoarthritis;    Strontium ranelate;    Cartilage;    Osteophytes;    Subchondral bone;    Micro-CT;   

DOI  :  10.1186/s12891-017-1399-2

 received in 2016-07-12, accepted in 2017-01-11,  发布年份 2017

来源: Springer

【 摘 要 】

BackgroundOsteoarthritis (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.MethodThirty-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.ResultsBoth 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.ConclusionsSR (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.

【 授权许可】

CC BY   
© The Author(s). 2017