The treatment of human periodontal diseases relies on mechanical and antimicrobial suppression of the etiologic bacteria. The ability to alter the progression of periodontitis by additionally blocking host pathways involved in the destructive process is an area of current research. Prostaglandins and other metabolites of arachidonic acid are believed to be important host mediators of the bone resorption of diseases such as periodontitis. We have previously examined the effect of inhibitors of prostaglandin production, non-steroidal anti-inflammatory drugs (NSAIDs), on inhibiting alveolar bone loss in beagles. The present study was designed to examine the effect of the NSAID, flurbiprofen, on slowing the radiographic loss of alveolar bone in the human. Fifty-six individuals with radiographic evidence of alveolar bone loss were recruited for study. Forty-four patients remained in the study for the data analysis of loss of alveolar bone. Following a 6 month baseline pretreatment period to measure the radiographic progression of bone loss, half of the patients were administered flurbiprofen, 50 mg. b.i.d., while half were administered a placebo. All patients received a subgingival scaling and pumice by a hygienist every 6 months. The rate of alveolar bone loss in a 2 year treatment period was compared to the baseline 6 month pretreatment period within and between patient groups. Throughout the study, teeth exhibiting obvious loss of bone were exited from study and treated with conventional mechanical therapy. At the end of the pretreatment period both patient groups had a similar mean rate of alveolar bone loss.(ABSTRACT TRUNCATED AT 250 WORDS)

The nonsteroidal anti-inflammatory drug, flurbiprofen, a potent cyclooxygenase inhibitor, significantly decreases the resorption of alveolar bone in naturally occurring chronic destructive periodontal disease in beagles. This observation indicates that arachidonic acid metabolites are important in the alveolar bone loss of periodontitis and suggests a use for flurbiprofen in the management of bone resorption disease.

Aspirin (ASA) and indomethacin are inhibitors of prostaglandin synthesis and reduce bone resorption in tissue culture stimulated by preparations obtained from human gingival tissue. In a retrospective study, we attempted to determine whether ASA or ASA plus indomethacin exert a bone resorption inhibiting effect on human alveolar bone. Dental radiographs of 75 patients with a history of arthritis and long-term ingestion (greater than 5 years) of ASA were compared with dental radiographs of 75 healthy male volunteers from the VA Dental Longitudinal Study (DLS). Proximal bone loss was measured using a Schei Ruler graded on a 10-point scale. The data indicated that the ASA population presented with significantly fewer sites of 10% or greater mesial and distal bone loss than the healthy control population (P less than 0.05). Mean percentage bone loss for the entire dentition was also lower in the ASA group, although the difference was not statistically significant. As there is no evidence to suggest that inhibition of alveolar bone loss is a natural concomitant of the arthritic process, we conclude that the inhibition of bone loss found in this study was due to the chronic ingestion of ASA or ASA and indomethacin.

Goldhaber has described a transplantable mouse fibrosarcoma which enhances the resorption of bone in tissue culture (2, 3). When fragments of the tumor (HSDM1) were placed in the same culture vessel with mouse calvaria, marked resorption of the bone was observed. Fragments of HSDM1 tumor could be cultured alone, and the medium from such explants also s t i m u l a t e d bone resorption when it was added to calvaria in organ culture. These findings suggested that the tumor was synthesizing and secreting a bone resorption-stimulating factor. Results of our previous experiments revealed that the factor could be extracted from the tumor tissue and recovered from the medium of HSDM1 cells grown in monolayer culture (1). Of particular interest was the finding that the HSDM1 factor could be extracted into organic solvents, and that it had several chemical and biological properties of a prostaglandin.We have recently reported that HSDM1 cells in culture synthesize and secrete large amounts of prostaglandin E2 (4). In the present report, we wish to present evidence that leads us to conclude that the bone resorption-stimulating factor produced b y the HSDM1 tumor is prostaglandin Ee. Materials and MethodsThe HSDM1 Tumor.--A fibrosarcoma was induced in a Swiss albino mouse by subcutaneous implantation of a Millipore filter (5, 6). The tumor has been passed serially in mice of the same strain for more than a decade. Excised tumor from a donor mouse is minced into