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The aim of the present study was to investigate the local effect of 10% doxycycline and 1% alendronate combined with poly(lactic-co-glycolic acid) (PLGA) on bone repair. Thirty rats were divided into three groups, as follows: control group (CG), drug group (DG), and vehicle-PLGA group (VG). Bone defect was created in the right femur and filled with the following: blood clot (CG); PLGA gel, 10% doxycycline and 1% alendronate (DG); or vehicle-PLGA (VG). The animals were euthanized 7 or 15 days after surgery. Bone density, bone matrix and number of osteoclasts were quantified. At 7 days, the findings showed increased density in DG (177.75 ± 76.5) compared with CG (80.37 ± 27.4), but no difference compared with VG (147.1 ± 41.5); no statistical difference in bone neoformation CG (25.6 ± 4.8), VG (27.8 ± 4), and DG (18.9 ± 7.8); and decrease osteoclasts in DG (4.6 ± 1.9) compared with CG (26.7 ± 7.4) and VG (17.3 ± 2.7). At 15 days, DG (405.1 ± 63.1) presented higher density than CG (213.2 ± 60.9) and VG (283.4 ± 85.8); there was a significant increase in percentage of bone neoformation in DG (31.5 ± 4.2) compared with CG (23 ± 4), but no difference compared with VG (25.1 ± 2.9). There was a decreased number of osteoclasts in DG (20.7 ± 4.7) and VG (29.5 ± 5.4) compared with CG (40 ± 9.4). The results suggest that the association of 10% doxycycline and 1% alendronate with PLGA-accelerated bone repair.