Skip Navigation LinksHome > March 15, 2009 - Volume 34 - Issue 6 > Short-term Osteoclastic Activity Induced by Locally High Con...
doi: 10.1097/BRS.0b013e3181952695
Basic Science

Short-term Osteoclastic Activity Induced by Locally High Concentrations of Recombinant Human Bone Morphogenetic Protein–2 in a Cancellous Bone Environment

Toth, Jeffrey M. PhD*; Boden, Scott D. MD†; Burkus, J Kenneth MD‡; Badura, Jeffrey M. MS§; Peckham, Steven M. PhD§; McKay, William F. ME§

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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. Overfilled-hyperconcentrated 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 hyperconcen-trating 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.

© 2009 Lippincott Williams & Wilkins, Inc.

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