Short-term Osteoclastic Activity Induced by Locally High Concentrations of Recombinant Human Bone Morphogenetic Protein–2 in a Cancellous Bone Environment
Study Design. An experimental study investigating osteoclastic activity induced by rhBMP-2 in sheep.
Objective. To examine the effects of increasing local rhBMP-2 concentration on osteoclastic response and peri-implant bone resorption.
Summary of Background Data. Level I clinical studies have established the safe and effective volume and concentration of rhBMP-2 delivered on an absorbable collagen sponge. However, peri-implant bone resorption appearing as decreased mineral density has been observed radiographically in rare instances after implantation of rhBMP-2 on an absorbable collagen sponge (rhBMP-2/ACS).
Methods. Bilateral corticocancellous defects were created in the distal femora of 30 adult sheep. Combinations of rhBMP-2/ACS implant volume (V) (1V = normal fill or 2V = overfilled) and rhBMP-2 solution concentration (⤫) (1 ⤫ normal concentration or 3.5 ⤫ = hyperconcentrated) resulted in local rhBMP-2 concentrations of 0⤫, 1⤫, 2⤫, 3.5⤫, and 7⤫ the estimated effective concentration for this model. Faxitron radiography, quantitative CT, histology, and quantitative
histomorphometry were conducted in a blinded fashion to analyze the effect of the treatments.
Results. At 1 week, the normal fill-normal concentration implants (1⤫) produced the least transient osteoclastic activity resulting in limited peri-implant resorption. Overfilledhyperconcentrated implants (2⤫, 3.5⤫) demonstrated moderate resorption zones. Overfilled-hyperconcentrated implants (7⤫) demonstrated extensive osteoclastic activity and marked resorption. Results at 4 and 8 weeks revealed dense osteoid and bone in the voids with progressive bony healing. Control defects showed no osteoclastic activity with little to no bony healing.
Conclusion. Increasing the local rhBMP-2 concentration by overfilling the defect with rhBMP-2/ACS or hyper-concentrating the rhBMP-2 solution on the absorbable collagen sponge led to a concentration-dependent osteoclastic resorption of peri-implant bone. The osteoclastic effect was transient, and progressive healing took place over the 8-week survival period.