ALENDRONATE INCREASES SKELETAL MASS OF GROWING RATS DURING UNLOADING BY INHIBITING RESORPTION OF CALCIFIED CARTILAGE

Loss of bone mass during periods of skeletal unloading remains an impo rtant clinical problem. To determine the extent to which resorption co ntributes to the relative loss of bone during skeletal unloading of th e growing rat and to explore potential means of preventing such bone l oss, 0.1 mg P/kg alendronate was administered to rats before unloading of the hindquarters. Skeletal unloading markedly reduced the normal i ncrease in tibial mass and calcium content during the 9 day period of observation, primarily by decreasing bone formation, although bone res orption was also modestly stimulated. Alendronate not only prevented t he relative loss of skeletal mass during unloading but led to a dramat ic increase in calcified tissue in the proximal tibia compared with th e vehicle-treated unloaded or normally loaded controls. Bone formation , however, assessed both by tetracycline labeling and by [H-3]proline and Ca-45 incorporation, was suppressed by alendronate treatment and f urther decreased by skeletal unloading. Total osteoclast number increa sed in alendronate-treated animals, but values were similar to those i n controls when corrected for the increased bone area. However, the os teoclasts had poorly developed brush borders and appeared not to engag e the bone surface when examined at the ultrastructural level. We conc lude that alendronate prevents the relative loss of mineralized tissue in growing rats subjected to skeletal unloading, but it does so prima rily by inhibiting the resorption of the primary and secondary spongio sa, leading to altered bone modeling in the metaphysis.