OBJECTIVETo observe the release kinetics of methotrexate-loaded calcium phosphate cement (MTX-CPC) implanted in vivo and histologically investigate its resorption and osteogenesis.

METHODSMTX-CPC consisting of 1% methotrexate (MTX) (weight/weight) was pre-set and implanted into femoral muscles of 24 New Zealand rabbits. The in vivo MTX release kinetics was determined on the 1st, 2nd, 5th, 10th, 15th, 20th, 25th, and 30th post-implantation day. The local concentrations and the residual percentage of MTX were determined. Then the pre-set MTX-CPC was implanted into femoral condyle. Calcium phosphate cement (CPC) without MTX was used as a control. The femurs were harvested at the 1st day and the 1st, 3rd, and 6th month and examined by X ray. Then histomorphometric analyses including percentage of newly formed bone and amount of osteoblast and osteoclast were performed.

RESULTSThe MTX release kinetics in vivo confirmed that MTX-CPC was a monolithic matrix system, with a burst effect in the initial stage and a sudden drop thereafter. The local concentration of the released MTX was 0.372 μg/ml on the 30th post-implantation day; with a concentration higher than the effective concentration,the incorporated MTX was expected to be continuously released over the following 2-3 months. Both MTX-CPC and CPC showed good biodegradability and osteoconduction. Although the release of MTX had an inhibitory effect on osteogenesis, especially in the initial stage, the area of newly formed bone, the amount of osteoblasts, and the amount of osteoclasts were not significantly different between MTX-CPC group and CPC group on the 6th post-implantation month.

CONCLUSIONSMPX-CPC system is an effective drug delivery system. Both MTX-CPC and CPC has good biodegradability and osteoconduction. Therefore,MTX-CPC system can be an ideal material for filling defects and controlling local recurrence.