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 also 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 mu g; 60 mu g; 240 mu g) and untreated) surrounded by a 0.75mm empty gap, were inserted into the distal femurs of each of twelve canines. Zoledronate IV (0.1mg/kg) was administered 10 days into the observation period of 4 weeks. Bone-implant specimens were evaluated by mechanical push-out test and histomorphometry. The 15 mu g implants had the best fixation on all mechanical parameters and largest surface area covered with new bone compared to the untreated, 60 and 240 mu g implants, as well as the highest volume of new bone in the implant gap compared to 60 and 240 mu g implants. The 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. (c) 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:1406-1414, 2018.