Histomorphologic Changes in the Mandibular Condyle of Acromegaly-like Rats

Objectives: To clarify the detailed mechanisms of the elongation of the ascending ramus in acromegalic patients, we investigated the morphological changes in the mandible and histopathological changes in the mandibular condyle of acromegaly-like rat model recently developed by exogenous insulin-like growth factor I (IGF-I). Methods: Human recombinant IGF-I (SOMAZON; Astellas Pharm Inc.) (640mg/day) was continuously subcutaneously infused into 10-week-old male rats for 4 weeks (n=12). The control sham-operated animals were injected with saline alone (n=12). Twelve rats (6 from each group) were sacrificed immediately on ending administration at 14 weeks of age. Another 12 rats (6 from each group) were housed for an additional 4 weeks after administration ended. Morphological analysis on the mandible and measurement of bone mineral density on the mandibular condyle were performed on lateral cephalometric image using soft X-ray equipment (SOFTEX Type CMB, SOFTEX Corp.). Cartilaginous layer width, bone matrix volume and the number of osteoblasts and osteoclasts were measured on the mandibular condylar coronal sections.Results: During and after IGF-I administration, mandibular condylar length significantly increased in the IGF-I group (p < 0.01). During IGF-I administration, bone mineral density, cartilaginous layer width, bone matrix volume and the number of osteoblasts in the mandibular condyle significantly increased in the IGF-I group (p < 0.05), unlike the number of osteoclasts. Such changes in the condyle disappeared after discontinuation of IGF-I administration.Conclusions: These findings suggest that mandibular protrusion in patients with acromegaly might be evoked by superfluous elongation of mandibular condyle presumably induced by endochondral ossification caused by high serum levels of IGF-I. This study was supported in part by a grant-in-aid for scientific research (No. 18791608, 19791631) from the Japanese Ministry of Education, Culture, Sports, Science and Technology.