Development of a ceramic device for the continuous local delivery of steroids

Testosterone has been shown to stimulate bone healing. However, large doses of testosterone have been associated with liver damage and prostate enlargement. Sustained release of testosterone by a device placed next to a bone fracture could deliver effective amounts of the steroid necessary for bone healing without the adverse side effects associated with oral delivery or intramuscular injection. The release of 1 mg of testosterone into 1 ml of 50% ethanol from one-hour calcined hydroxyapatite (HA) ceramics (n = 6) and twelve-hour calcined HA ceramics (n = 6) was measured over four days. The twelve-hour calcined HA ceramics exhibited a consistently slower testosterone release. A 200mg HA/0.1% PLA/gentamicin (1mg) ceramic cylinder containing 0, 0.5, 1.0, or 1.5 mg testosterone was placed adjacent to a 4 x 1 x 1 mm femoral defect created in four equal groups of twenty-seven castrated male Sprague Dawley rats. After four weeks, none of the ceramics contained any residual testosterone. Histological examination showed that the traumatized bone of the animals implanted with testosterone-containing ceramics healed faster for the first four weeks than the controls. This data suggests that the twelve-hour calcined HA should be used to extend the release of testosterone to enhance healing of traumatized bone.