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Effects of weekly administrations of alendronate+clodronate on young mouse tibia: localized action at the proximal growth plate.

Abstract
Alendronate (A), a typical aminobisphosphonate (aminoBP), has a strong bone-resorption-inhibitory activity (BRIA). However, like other aminoBPs it has inflammatory side effects. In contrast, the BRIA of clodronate (C), a non-aminoBP, is much weaker, and in animal experiments it suppresses aminoBP-induced inflammatory reactions. In the present study, we examined the effects of weekly administrations of A (1.6 micro mol/kg) + C (160 micro mol/kg) on the tibias in young mice and compared them to those induced by A or C alone. Radiophotography showed that A increased bone density at a selective site in the tibia. Indeed, one week after the final injection of A (given alone), clear sclerotic lines (tentatively called BP-lines) were visible at sites corresponding to the location of the growth plate at the time of the each injection. C also produced BP-lines, although they were weaker than those produced by A. Combined administration of A and C produced similar BP-lines as seen in mice given A alone. These results together with other physicochemical effects of A on the tibia suggest that (1) each injection of A and C inhibits bone resorption selectively and transiently at the tibial growth plate in young mice, although minor effects on other sites cannot be excluded, and (2) the combination of A and C keeps still a strong BRIA. Our findings may suggest a strategy for the prevention or reduction of some inflammatory side effects of A or other aminoBPs.
AuthorsY Monma, H Funayama, H Mayanagi, Y Endo
JournalCalcified tissue international (Calcif Tissue Int) Vol. 74 Issue 1 Pg. 115-21 (Jan 2004) ISSN: 0171-967X [Print] United States
PMID14564433 (Publication Type: Journal Article)
Chemical References
  • Anti-Inflammatory Agents
  • Clodronic Acid
  • Calcium
  • Alendronate
Topics
  • Alendronate (administration & dosage, chemical synthesis, pharmacology)
  • Animals
  • Anti-Inflammatory Agents (administration & dosage, chemical synthesis, pharmacology)
  • Calcium (analysis)
  • Clodronic Acid (administration & dosage, chemical synthesis, pharmacology)
  • Drug Administration Schedule
  • Drug Therapy, Combination
  • Growth Plate (drug effects)
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Radiography
  • Tibia (chemistry, diagnostic imaging, drug effects)

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