Short-term osteoclastic activity induced by locally high concentrations of recombinant human bone morphogenetic protein-2 in a cancellous bone environment

• Published in: Spine (Philadelphia, Pa. 1976) Vol. 34; no. 6; p. 539
• Main Authors: Toth, Jeffrey M, Boden, Scott D, Burkus, J Kenneth, Badura, Jeffrey M, Peckham, Steven M, McKay, William F
• Format: Journal Article
• Language: English
• Published: United States 15.03.2009
• Subjects: Absorbable Implants; Animals; Bone Morphogenetic Protein 2 - pharmacology; Bone Resorption - diagnostic imaging; Bone Resorption - drug therapy; Bone Resorption - pathology; Disease Models, Animal; Dose-Response Relationship, Drug; Female; Femur - cytology; Femur - diagnostic imaging; Femur - surgery; Fracture Healing - drug effects; Humans; Osteoclasts - drug effects; Osteoclasts - physiology; Recombinant Proteins - pharmacology; Sheep; Tomography, X-Ray Computed
• DOI: 10.1097/brs.0b013e3181952695

An experimental study investigating osteoclastic activity induced by rhBMP-2 in sheep. To examine the effects of increasing local rhBMP-2 concentration on osteoclastic response and peri-implant bone resorption. 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). 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 (x) (1x = normal concentration or 3.5x = hyperconcentrated) resulted in local rhBMP-2 concentrations of 0x, 1x, 2x, 3.5x, and 7x 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. At 1 week, the normal fill-normal concentration implants (1x) produced the least transient osteoclastic activity resulting in limited peri-implant resorption. Overfilled-hyperconcentrated implants (2x, 3.5x) demonstrated moderate resorption zones. Overfilled-hyperconcentrated implants (7x) 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. Increasing the local rhBMP-2 concentration by overfilling the defect with rhBMP-2/ACS or hyperconcentrating 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.