No abstract

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 µg; 60 µg; 240 µg) and untreated) 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 10 days into the observation period of 4 weeks. Bone-implant specimens were evaluated by mechanical push-out test and histomorphometry. The 15 µg implants had the best fixation on all mechanical parameters and largest surface area covered with new bone compared to the untreated, 60 and 240 µg implants, as well as the highest volume of new bone in the implant gap compared to 60 and 240 µg 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. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:1406-1414, 2018.

Aims We wanted to evaluate the effects of a bone anabolic agent (bone morphogenetic protein 2 (BMP-2)) on an anti-catabolic background (systemic or local zoledronate) on fixation of allografted revision implants. Methods An established allografted revision protocol was implemented bilaterally into the stifle joints of 24 canines. At revision surgery, each animal received one BMP-2 (5 µg) functionalized implant, and one raw implant. One group (12 animals) received bone graft impregnated with zoledronate (0.005 mg/ml) before impaction. The other group (12 animals) received untreated bone graft and systemic zoledronate (0.1 mg/kg) ten and 20 days after revision surgery. Animals were observed for an additional four weeks before euthanasia. Results No difference was detected on mechanical implant fixation (load to failure, stiffness, energy) between local or systemic zoledronate. Addition of BMP-2 had no effect on implant fixation. In the histomorphometric evaluation, implants with local zoledronate had more area of new bone on the implant surface (53%, p = 0.025) and higher volume of allograft (65%, p = 0.007), whereas implants in animals with systemic zoledronate had the highest volume of new bone (34%, p = 0.003). Systemic zoledronate with BMP-2 decreased volume of allograft by 47% (p = 0.017). Conclusion Local and systemic zoledronate treatment protects bone at different stages of maturity; local zoledronate protects the allograft from resorption and systemic zoledronate protects newly formed bone from resorption. BMP-2 in the dose evaluated with experimental revision implants was not beneficial, since it significantly increased allograft resorption without a significant compensating anabolic effect. Cite this article: Bone Joint Res 2021;10(8):488–497.