Improved handling characteristics of bone substitute materials may facilitate surgical handling. However, the respective modifications should not alter the biological activity. For comparison of a granular and a putty form of two silicaenhanced bone substitute materials, in 30 rabbits, bilateral bone defects were created in the femoral condyle and randomly filled with (1) sintered, silica-enhanced (0.8 wt%) hydroxyapatite (ACg, n ¼ 15); (2) ACg plus resorbable polymer (ACp, n ¼ 15); (3) non-sintered silica-enhanced hydroxyapatite (hydroxyapatite/SiO 2 ratio:61:39 wt%; NBg, n ¼ 15); and (4) NBg plus matrix of resorbable polymer (NBp, n ¼ 15). After 4, 8, and 12 weeks, respectively, newformed bone, remaining bone substitute materials, and amount of soft tissue were quantified histomorphometrically. After four weeks, new-formed bone was increased for NBg/NBp in which NBp showed significantly less remaining bone substitute materials when compared to ACg. After two months, the highest amount of new-formed bone and the least remaining bone substitute materials were seen for NBg and NBp. ACp had less remaining bone substitute material when compared to ACg. In addition, amount of soft tissue was significantly enhanced in NBp when compared to ACg and NBg. After 12 weeks, NBp had significantly lower remaining bone substitute material when compared to ACg. Amount of soft tissue was significantly increased in NBp when compared to ACg and NBg. In accordance, based on an early increase of new-formed bone, a lower amount of remaining bone substitute material, and as well as a distinct degradation, superiority of the non-sintered bone substitute material to the sintered bone substitute material was seen. The effect of the resorbable polymer to each bone substitute material can be supposed to be rather marginal.