The effects of direct factor Xa inhibitor (Rivaroxaban) on the human osteoblastic cell line SaOS2.
Thromboprophylaxis reduces the risk of surgery-related deep vein thrombosis, but anticoagulants were associated with systemic osteoporosis, a known risk factor for poor fracture healing. Rivaroxaban (XARELTO(®)) is a novel anticoagulant with specific ability to inhibit factor Xa, a serine endopeptidase, which plays a key role in coagulation. This study investigated the direct effects of rivaroxaban on bone biology using an in vitro cell culture model from the human female osteoblastic cell line SaOS2. Cells at subconfluence were treated for 24 hr with different concentrations of rivaroxaban and analyzed for DNA synthesis and creatine kinase- and alkaline phosphatase-specific activities, and were treated 21 days for analyzing mineralization. Rivaroxaban (0.01-50 μg/ml) dose-dependently inhibited up to 60% DNA synthesis of the cells. Creatine kinase-specific activity was also inhibited dose-dependently to a similar extent by the same concentrations. Alkaline phosphatase-specific activity was dose-dependently inhibited but only up to 30%. Cell mineralization was unaffected by 10 μg/ml rivaroxaban. This model demonstrated a significant rivaroxaban-induced reduction in osteoblastic cell growth and energy metabolism, and slight inhibition of the osteoblastic marker, alkaline phosphatase, while osteoblastic mineralization was unaffected. These findings might indicate that rivaroxaban inhibits the first stage of bone formation but does not affect later stages (i.e., bone mineralization).
Division of Orthopedic Surgery, Tel Aviv Sourasky Medical Center, Tel-Aviv, Israel. roygigimd@gmail.com
Roy
R
Gigi
Moshe
M
Salai
Oleg
O
Dolkart
Ofir
O
Chechik
Sarah
S
Katzburg
Naftali
N
Stern
Dalia
D
Somjen
D000469:Alkaline Phosphatase / Q000378:metabolism; D000925:Anticoagulants / Q000494:pharmacology*; D002113:Calcification, Physiologic / Q000187:drug effects*; D002460:Cell Line; D003402:Creatine Kinase / Q000378:metabolism; D004247:DNA / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D015951:Factor Xa / Q000378:metabolism; D065427:Factor Xa Inhibitors; D005260:Female; D006801:Humans; D009025:Morpholines / Q000494:pharmacology*; D010006:Osteoblasts / Q000166:cytology / Q000378:metabolism*; D000069552:Rivaroxaban; D013876:Thiophenes / Q000494:pharmacology*
D000925:Anticoagulants; D065427:Factor Xa Inhibitors; D009025:Morpholines; D013876:Thiophenes; D004247:DNA; D000069552:Rivaroxaban; D003402:Creatine Kinase; D000469:Alkaline Phosphatase; D015951:Factor Xa