The present study was undertaken to investigate the effects of long term administration of valproate that is commonly used in clinics and co-administration of alfacalcidol or alendronate with valproate on bone metabolism in growing rats. Bone mineral densities and serum bone makers were determined. The samples obtained from tibial metaphysis were then prepared for histological observation. As the results, valproate decreased the bone mineral density in both metaphysis and diaphysis with dose

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... physis with dose dependent manner. The magnitude of the decrease was greater in the diaphysis than metaphysis. Decreased bone volume was observed in all of groups treated with valproate. Although the levels of serum calcium were not affected, valproate increased the activities of acid phosphatase and alkaline phosphatase in the serum. The above results showed that valproate could induce bone loss in growing rats. Possible reason of the decrease was due to bone loss. Combined administration of alfacalcidol or alendronete prevented the osteopnenia induced by valproate. Therefore, these drugs cloud have useful efficacy to prevent osteopenia induced by valproate.