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§

Collapse Box


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.

Follow Us!



Article Level Metrics

Search for Similar Articles
You may search for similar articles that contain these same keywords or you may modify the keyword list to augment your search.