The maintenance of alveolar bone is a major clinical objective in dentistry. This is particularly difficult following local inflammatory episodes such as those of periodontitis or following loss of the dentition (residual ridge resorption). We present evidence in beagle dogs that local infusion of prostaglandin E1 (PGE) produces a dramatic, localized formation of alveolar bone which exhibits a normal lamellar architecture and mineralization pattern when evaluated by fluorescence microscopy and microradiography. The present proposal examines dose and time parameters for an optimal osteogenic response and tests the skeletal integration of this newly formed bone by following bone turnover through two remodeling cycles in this mandible. In addition, we shall measure the local tissue concentration of PGE and its metabolites at mineralized and soft tissue sites near and distant to the newly formed alveolar bone. These studies will employ microsurgical methods to assure a precise localized delivery of PGE via cannulated osmotic minimum, morphological, histomorphometric, microradiographic and fluorescent microscopic methods to evaluate the tissue level response to PGE infusions at various doses and times and measurements of local levels of PGE and metabolites by RIA and HPLC to determine local concentrations before, during and following the localized induction of new alveolar bone. Future studies will be directed at analyses of cell metabolism and turnover, will examine the mechanisms by which this local osteogenic response is mediated and will explore the ability of this newly formed bone to reverse residual ridge resorption and repair osseous defects in the jaws. This work is expected to have widespread use in treatment of the generalized and localized osteopenias as well as in the management of skeletal repair following trauma or surgical resection.
|Cielinski, M J; Marks Jr, S C (1994) Understanding bone cell biology requires an integrated approach: reliable opportunities to study osteoclast biology in vivo. J Cell Biochem 56:315-22|
|Miller, S C; Marks Jr, S C (1994) Effects of prostaglandins on the skeleton. Clin Plast Surg 21:393-400|
|Marks Jr, S C; Miller, S C (1994) Local delivery of prostaglandin E1 induces periodontal regeneration in adult dogs. J Periodontal Res 29:103-8|
|Miller, S C; Marks Jr, S C (1993) Alveolar bone augmentation following the local administration of prostaglandin E1 by controlled-release pellets. Bone 14:587-93|
|Miller, S C; Marks Jr, S C (1993) Local stimulation of new bone formation by prostaglandin E1: quantitative histomorphometry and comparison of delivery by minipumps and controlled-release pellets. Bone 14:143-51|