Microvascular events in bone marrow related to development of and recovery from bone atrophy in thiotepa-treated rats

To clarify the relationship of microvascular events in the bone marrow to the development of and the recovery from bone atrophy, we examined quantitatively and qualitatively trabecular bone, sinusoids and haematopoietic tissue in the metaphysis of the tibia of rats given thiotepa, an antitumour drug derived from nitrogen mustards. The administration of thiotepa rapidly reduced the number of haematopoietic cells causing significant dilatation of the sinusoids and atrophy of the trabecular bone 1 day after the injection. However, these changes were transient; regeneration of haematopoietic cells and normalization of the dilated sinusoids started 3 days after the injection, and the atrophied trabecular bone gradually returned to normal starting 6 days after the injection. These results imply that an extreme decrease in velocity and margination of sinusoidal blood flow following marked dilatation due to a decrease in haematopoietic cells cause atrophy of the trabecular bone, and that normalization of the sinusoidal blood flow following regeneration of haematopoietic cells leads to recovery from atrophy of trabecular bone.