High doses of bone morphogenetic protein 2 induce structurally abnormal bone and inflammation in vivo.

The major Food and Drug Association-approved osteoinductive factors in wide clinical use are bone morphogenetic proteins (BMPs). Although BMPs can promote robust bone formation, they also induce adverse clinical effects, including cyst-like bone formation and significant soft tissue swelling. In this study, we evaluated multiple BMP2 doses in a rat femoral segmental defect model and in a minimally traumatic rat femoral onlay model to determine its dose-dependent effects. Results of our femoral segmental defect model established a low BMP2 concentration range (5 and 10 µg/mL, total dose 0.375 and 0.75 µg in 75 µg total volume) unable to induce defect fusion, a mid-range BMP2 concentration range able to fuse the defect without adverse effects (30 µg/mL, total dose 2.25 µg in 75 µg total volume), and a high BMP2 concentration range (150, 300, and 600 µg/mL, total dose 11.25, 22.5, and 45 µg in 75 µg total volume) able to fuse the defect, but with formation of cyst-like bony shells filled with histologically confirmed adipose tissue. In addition, compared to control, 4 mg/mL BMP2 also induced significant tissue inflammatory infiltrates and exudates in the femoral onlay model that was accompanied by increased numbers of osteoclast-like cells at 3, 7, and 14 days. Overall, we consistently reproduced BMP2 side effects of cyst-like bone and soft tissue swelling using high BMP2 concentration approaching the typical human 1500 µg/mL.

Myospherulosis of the mastoid antrum: a case report.

Myospherulosis is a recently discovered iatrogenic disease caused by the implantation during surgery of mineral oil- or petrolatum-based products into various tissues. The condition results from the action of lipid substances on extravasated erythrocytes. The case report presented is the first detailed description of this uncommon, unique inflammatory lesion occurring in the mastoid and is the second otitic case reported in the literature. The lesion mimicked recurrent cholesteatoma 6 years following an intact canal wall mastoidectomy. As in myospherulosis of the paranasal sinuses, the symptoms and findings of otitic myospherulosis are those of the preceding disease.