Effect of monosodium olpadronate on osteoclasts and megakaryocytes: an in vivo study

Bisphosphonates (BPs) are widely used to treat several bone pathologies. Their action on bone cells depends on cell lineage, promoting or preventing apoptosis in osteoclastic and osteoblastic lineage respectively. Bone cells and bone marrow (BM) are closely related. Bone marrow megakaryocytes regulate bone turn-over. The objective of this in vivo experimental work was to evaluate the effect of olpadronate (OPD) on osteoclasts (Ocs) and megakaryocytes (Mks) using histomorphometric, histochemical, and immunohistochemical methods. Healthy female Wistar rats were used: experimental and Sham animals received OPD or vehicle during five weeks. After sacrifice, kidneys, liver, spleen, femurs and tibiae were dissected and fixed for histological processing. H and E, histochemical detection of TRAP and immunohistochemical detection of TUNEL and RANKL were performed. Results showed increased bone volume and number of Ocs, larger Ocs with more nuclei, increase in Oc apoptosis, and loss of polarity in OPD-treated animals. Statistically significant association was found between apoptotic morphology and RANKL expression in Ocs. BM and spleen showed a significant increase in Mk number. The number of RANKL+Ocs and MKs per unit area increased. The increase in Oc apoptosis did not counteract the increase in Oc recruitment thus resulting in an increase in Oc number. Ocs recruitment could be associated with RANKL expression in Mks and apoptotic Ocs. The effect of OPD and other BPs on Mks should be investigated further to elucidate the mechanism by which BPs act on the bone-bone marrow functional unit, and understand the therapeutic implications of BPs.