This study examined effects of bone bonding and nonbonding implants on parameters associated with matrix vesicle-mediated primary bone formation, matrix vesicle alkaline phosphatase and phospholipase A2 specific activities, and phosphatidylserine content. Tibia marrow ablation followed by implantation of KG-Cera, Mina 13 (bonding), KGy-213, or M 8/1 (nonbonding) was used as the experimental model. Postsurgery, matrix vesicle-enriched microsomes (MVEM) were isolated from implanted and contralateral limbs. MVEM alkaline phosphatase and phospholipase A2 were stimulated adjacent to bonding implants with similar, though reduced, effects contralaterally. Alkaline phosphatase exhibited slight stimulation in nonbonding tissue; phospholipase A2 was inhibited or unchanged in treated and contralateral limbs. Phosphatidylserine content of MVEM was differentially affected by the implant materials. Thus, MVEM are modulated by implant materials locally and systemically. The data demonstrate that the model is a biologically relevant diagnostic for assessing the tissue/implant interface, primary calcification is affected by implant materials, and implant-specific effects are detected in the contralateral unimplanted limb.