|Abstract / Summary
Total joint arthroplasties are a good and efficient treatment to alleviate symptoms of end stage arthritis. But athroplasties can fail and is primarily due to aseptic loosening caused by osteolysis or poor implant osseointegration. Lost bone can be replaced with allograft to provide initial stability to implants. Combined anabolic and anti-catabolic treatment can potentially improve allograft incorporation and implant osseointegration.
Bone morphogenetic protein 2 (BMP-2) stimulates osteoblast formation and activity, but also invokes an indirect catabolic response by stimulating osteoclast activity. Nitrogen-containing bisphosphonates are potent inhibitors of osteoclast activity.
The aim of the present thesis was to investigate, whether the initial implant fixation and osseointegration of experimental orthopedic implants could be improved by combining a bone anabolic agent (BMP-2) with an anti-catabolic agent (zoledronate). All studies with BMP-2 were conducted on an anti-catabolic background.
All three studies in this dissertation were conducted in a canine animal model and covered an observation period of 4-12 weeks. Mechanical and histomorphometric evaluation were used to measure the effect of the treatment.
Study I investigated unloaded BMP-2 coated (15 µg, 60 µg and 240 µg) and untreated implants surrounded by a 2.5-mm gap impacted with allograft. All animals received zoledronate (0.1 mg/kg) IV 10 days postoperatively. The untreated control implants had the best mechanical fixation, best osseointegration, and largest volume of retained allograft in the peri-implant gap. Mechanical fixation, osseointegration, and volume of allograft decreased as the BMP-2 dose increased.
Study II investigated unloaded BMP-2 (15 µg, 60 µg and 240 µg) coated and untreated implants surrounded by an empty 0.75 mm gap. All animals received zoledronate (0.1 mg/kg) IV 10 days postoperatively. Implants coated with 15 µg of BMP-2 had the best mechanical fixation. This was corroborated by histomorphometric findings of best osseointegration and highest volume of new bone in the peri-implant gap.
Study III investigated loaded intraarticular revision implants surrounded by a 1.1-mm gap with allograft. Each animal received 2 implants. One implant was implanted into each medial femur condyle in each knee. Each animal received one implant coated with rhBMP-2 (5 µg) and an untreated control implant was implanted in the contralateral knee. Half of the animals received allograft soaked in zoledronate at the revision surgery and the other half received zoledronate (0.1 mg/kg) IV 10 and 20 days after the revision surgery. BMP-2 did not improve implant osseointegration or fixation. Local zoledronate showed the best results for retaining allograft, whereas systemic zoledronate accrued new bone.
The studies demonstrate that BMP-2 within a relative narrow dose range exhibits significant and different catabolic and anabolic effects depending on the implant bone interface conditions. BMP-2 showed no positive effect to augment implants with allograft (Study I and III). In contrast, BMP-2 improved implant fixation and osseointegration of implants without direct bone contact (Study II). Study III confirmed that local zoledronate decreased allograft resorption, and that systemic zoledronate accrued a larger volume of new bone compared to local zoledronate.