Effects of clodronate and alendronate on local and systemic changes in bone metabolism in rats with adjuvant arthritis.
We compared the effects of nonaminobisphosphonate (nonamino-BP; clodronate) and amino-BP (alendronate) on the changes in local and systemic bone metabolism associated with chronic inflammation in adjuvant-arthritis rats. A given rat received one of the BPs orally each day for 28 days from the day of adjuvant inoculation. Hindpaw swelling was observed from day 10 after adjuvant inoculation up to day 28 (peak, day 21). Clodronate slightly decreased the hindpaw swelling at doses of 12.5 and 25 mg/kg, p.o./day; however, alendronate (0.125-0.5 mg/kg) did not. Radiological examination of the distal limb joints revealed that only clodronate decreased bone deformation. Urinary deoxypyridinoline increased as arthritis developed, and it was decreased by clodronate. On day 29, pQCT analysis of the 5th lumbar vertebra revealed trabecular bone loss and cortical bone thinning in the arthritis control group, leading to compressive strength being reduced. Both BPs prevented this bone loss and strength reduction. These data suggest that only clodronate decreases inflammation and local bone deformation, while both BPs inhibit the arthritis-related decreases in systemic bone mass and bone strength. Clodronate would be useful in the treatment of inflammation-induced bone deformation and osteopenia.
Itoh
Fumiaki
F
Department of Pharmacology, School of Pharmacy, Tokyo University of Pharmacy and Life Science, Tokyo, Japan. fumiaki_ito@pharm.kissei.co.jp
Aoyagi
Shigemi
S
Kusama
Hiroshi
H
Kojima
Masami
M
Kogo
Hiroshi
H
D019386:Alendronate / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D001169:Arthritis, Experimental / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D001842:Bone and Bones / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D004002:Clodronic Acid / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D010012:Osteogenesis / Q000187:drug effects; D051381:Rats; D011917:Rats, Inbred Lew
D004002:Clodronic Acid; D019386:Alendronate