Abstract
The present study aimed at investigating the effects of systemic administration of 1hydroxyethylidene-1,1-bisphosphonic acid (HEBP,1.0 mg P/day/kg b. w. ) on the recruitment and activation of osteoclastic lineage cells at discrete alveolar bone sites, namely sockets after extraction of the upper first molar and periodontal spaces surrounding the second molar roots. Five week-old male SD rats were used. Systemic-infusion of the agent was performed using an Alzet osmotic pump, which was implanted subcutaneously on the dorsal area and polyethylene tubing was inserted into the external jugular vein. The animals were sacrificed at 7 and 14 days after molar extraction and pump implantation. Maxillary specimens were dissected and then used for μCT observation and histomorphometric analysis. Osteoclastic lineage cells were identified using enzyme histochemistry for detection of activities of tartrate-resistant acid phosphatase (TRAP). In the control animals without administration of HEBP, the number of TRAP-positive mono- and multinuclear cells increased markedly at day 7 in the tooth sockets. Histomorphometric analysis regarding alveolar bone resorption activity and population of TRAP-positive cells showed that systemic HEBP delivery did not noticeably affect the recruitment of TRAP-positive cells in the tooth sockets and periodontium but caused inhibitory effects on osteoclastic maturation, i. e., multinucleation and development of ruffled processes and resorption lacunae. The appearance of apoptotic bodies under the HEBP regimen was distinguishable for mononuclear cells but not for multinucleated osteoclasts. Most remarkably, the above-mentioned multifaceted effects of HEBP on osteoclast lineage were site-specific, that is, prominent within the extraction sockets but only marginal in the root-surrounding periodontal space. This local variation in HEBP-dependent osteoclastic cell behavior may be explained by the accumulation and secondary release of HEBP in and from osteoid deposited during its systemic delivery period.
