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.