Healing in peri‐implant gap with BMP‐2 and systemic bisphosphonate is dependent on BMP‐2 dose—A canine study

The bone-implant interface of cementless orthopedic implants can be described as a series of uneven sized gaps with discontinuous areas of direct bone-implant contact. Bridging these voids and crevices by addition of an anabolic stimulus to increase new bone formation can potentially improve osseointegration of implants. Bone Morphogenetic Protein 2 (BMP-2) stimulates osteoblast formation to increase new bone formation but indirectly stimulates osteoclast activity. In this experiment we investigate the hypothesis that osseointegration, defined as mechanical push-out and histomorphometry, depends on the dose of BMP-2 when delivered as an anabolic agent with systemic administration of the anti-resorptive agent zoledronate to curb an increase in osteoclast activity. Four porous coated titanium implants (one with each of three doses of surface-applied BMP-2 (15 µg; 60 µg; 240 µg) and control) surrounded by a 0.75 mm empty gap, were inserted into the distal femurs of each of twelve canines. Zoledronate IV (0.1 mg/kg) was administered ten days into the observation period of four weeks. Bone-implant specimens were evaluated by mechanical push-out test and histomorphometry. 15 µg implants had the best fixation on all mechanical parameters and largest surface area covered with new bone compared to control, 60 µg and 240 µg implants, as well as the highest volume of new bone in the implant gap compared to 60 µg and 240 µg implants. Results in a canine implant model demonstrated that a narrow range of BMP-2 doses have opposite effects in bridging an empty peri-implant gap with bone, when combined with systemic zoledronate. This article is protected by copyright. All rights reserved