ABSTRACT
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.
Subject(s)
Bone Density Conservation Agents/pharmacology , Diphosphonates/pharmacology , Megakaryocytes/drug effects , Osteoclasts/drug effects , Acid Phosphatase/drug effects , Acid Phosphatase/metabolism , Animals , Apoptosis/drug effects , Apoptosis/physiology , Female , Immunohistochemistry , In Situ Nick-End Labeling , Isoenzymes/drug effects , Isoenzymes/metabolism , Megakaryocytes/metabolism , Osteoclasts/metabolism , RANK Ligand/drug effects , RANK Ligand/metabolism , Rats , Rats, Wistar , Tartrate-Resistant Acid PhosphataseABSTRACT
AIMS: To review a series of 23 consecutive patients with squamous cell carcinomas arising from oropharynx who underwent infra hyoid musculo-cutaneous flap reconstruction including soft palate in alternative to free radial forearm flap or maxillofacial prosthesis. Post operative radiotherapy was performed for all patients. RESULTS: Every reconstruction healed quickly without major wound complications. The functional results evaluated by speech and swallowing capacities, were good for 17 patients, fair for 4 patients and bad for 2. CONCLUSIONS: The infra hyoid musculo-cutaneous flap is a versatile, reliable and convenient flap suitable for repairing small and medium sized defects; it can be used in combination with other flaps, and in selected cases obviates the need for a microvascular free radial forearm flap or maxillofacial prosthesis.
