Abstract
In young adult mice the osteogenic response to artificial mechanical loading is unaffected by bisphosphonates suggesting that it primarily involves adaptive osteogenic modelling without accompanying resorption [1]. The aim of the present study was to use bisphosphonates to determine whether the mechanically adaptive response is similar in aged mice.
Female 19-month-old C57BL6/J mice were administered vehicle (saline) or the bisphosphonate Risedronate (15µg/kg) by daily subcutaneous injections from day zero. From day four, the right tibiae were subjected to loading every second day for two weeks, with the left limb as an internal non-loaded control. Mice were killed on day 21. Cortical and trabecular bone was analysed by µCT.
Loading resulted in greater trabecular thickness (Tb.Th) and increased cortical bone mass in the proximal tibia (37% site) by increasing cortical area (Ct.Ar), cortical thickness (Ct.Th), total tissue area (Tt.Ar) and polar moment of inertia (PMI) despite an increase in medullary area (Ma.Ar). As expected, loading had no significant effect on cortical bone in the distal tibia (75% site). Risedronate reduced trabecular structure model index (SMI), increased Ct.Th in both cortical sites and increased PMI in the 37% site. The combination of risedronate and loading did not alter the loading-related increase in Tb.Th but additively increased Ct.Ar, Ct.Th and PMI in the proximal tibia. Risedronate pre-treatment prevented the loading-related increase in Ma.Ar observed at the 37% cortical site. Loading did not alter the increase in Ct.Th due to risedronate treatment in the distal tibia.
In conclusion, the lack of any observed effect of risedronate on trabecular bone mass in these old mice differs from that reported in young mice [1], demonstrating that observations in the young cannot necessarily be extrapolated to the old. To the extent that the situation in old mice can be extrapolated to old humans, it appears that in cortical bone, risedronate treatment potentially confers the clinical benefit of increased bone mass. This benefit is increased when risedronate treatment is combined with loading since there is an additive positive increase in a number of cortical bone parameters, due to increased periosteal expansion unaccompanied by endosteal resorption.
1. Sugiyama et al (2011) Bone 49 133-139
Female 19-month-old C57BL6/J mice were administered vehicle (saline) or the bisphosphonate Risedronate (15µg/kg) by daily subcutaneous injections from day zero. From day four, the right tibiae were subjected to loading every second day for two weeks, with the left limb as an internal non-loaded control. Mice were killed on day 21. Cortical and trabecular bone was analysed by µCT.
Loading resulted in greater trabecular thickness (Tb.Th) and increased cortical bone mass in the proximal tibia (37% site) by increasing cortical area (Ct.Ar), cortical thickness (Ct.Th), total tissue area (Tt.Ar) and polar moment of inertia (PMI) despite an increase in medullary area (Ma.Ar). As expected, loading had no significant effect on cortical bone in the distal tibia (75% site). Risedronate reduced trabecular structure model index (SMI), increased Ct.Th in both cortical sites and increased PMI in the 37% site. The combination of risedronate and loading did not alter the loading-related increase in Tb.Th but additively increased Ct.Ar, Ct.Th and PMI in the proximal tibia. Risedronate pre-treatment prevented the loading-related increase in Ma.Ar observed at the 37% cortical site. Loading did not alter the increase in Ct.Th due to risedronate treatment in the distal tibia.
In conclusion, the lack of any observed effect of risedronate on trabecular bone mass in these old mice differs from that reported in young mice [1], demonstrating that observations in the young cannot necessarily be extrapolated to the old. To the extent that the situation in old mice can be extrapolated to old humans, it appears that in cortical bone, risedronate treatment potentially confers the clinical benefit of increased bone mass. This benefit is increased when risedronate treatment is combined with loading since there is an additive positive increase in a number of cortical bone parameters, due to increased periosteal expansion unaccompanied by endosteal resorption.
1. Sugiyama et al (2011) Bone 49 133-139
| Original language | English |
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| Publication status | Published - 8 Oct 2015 |