Inhibitory effect of bone resorption and inflammation with etidronate therapy in patients with rheumatoid arthritis for 3 years and in vitro assay in arthritis models.
This study was conducted to identify bone resorption and anti-inflammatory effects with intermittent cyclical etidronate therapy (ICET) in patients with rheumatoid arthritis, and anti-inflammatory effect of etidronate in vitro. We compared bone mineral density (BMD), urinary deoxypyridinoline (DPD) level, bone alkaline phosphatase (BAP) level and Larsen damage scores between the ICET and the non-ICET groups for 3 years. The levels of interleukin-6 (IL-6), prostaglandin E2 (PGE2), substance P and vascular endothelial growth factor (VEGF) in synovial cells from arthritis models were measured following the addition of etidronate. In the ICET group, BMD and BAP levels increased. Urinary DPD level and the Larsen damage score were significantly lower than that in the non-ICET group. In the in vitro study, the production of IL-6, PGE2, substance P and VEGF were inhibited in a dose-dependent manner. Bone resorption and destruction inhibition effect of etidronate remained for 3 years. In vitro study showed that the production of inflammatory cytokines and an angiogenesis factor were inhibited.
Yamamoto
Kaname
K
Department of Joint Disease and Rheumatism, Nippon Medical School, 1-1-5 Sendagi, Tokyo 113-8603, Japan.
Yoshino
Shinichi
S
Shue
Goukei
G
Nagashima
Masakazu
M
D000368:Aged; D000469:Alkaline Phosphatase / Q000032:analysis; D000596:Amino Acids / Q000652:urine; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000378:metabolism; D015519:Bone Density / Q000187:drug effects; D050071:Bone Density Conservation Agents / Q000627:therapeutic use*; D001862:Bone Resorption / Q000517:prevention & control*; D012968:Etidronic Acid / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D008875:Middle Aged
D000596:Amino Acids; D000893:Anti-Inflammatory Agents; D050071:Bone Density Conservation Agents; D015850:Interleukin-6; C036020:deoxypyridinoline; D000469:Alkaline Phosphatase; D012968:Etidronic Acid