Faculty Collaboration Database

Short-term osteoclastic activity induced by locally high concentrations of recombinant human bone morphogenetic protein-2 in a cancellous bone environment. Spine (Phila Pa 1976) 2009 Mar 15;34(6):539-50

Date

02/26/2009

Pubmed ID

19240666

DOI

10.1097/BRS.0b013e3181952695

Scopus ID

2-s2.0-65549116404 (requires institutional sign-in at Scopus site)   92 Citations

Abstract

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 (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.

RESULTS: 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.

CONCLUSION: 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.

Author List

Toth JM, Boden SD, Burkus JK, Badura JM, Peckham SM, McKay WF

Author

Jeffrey M. Toth PhD Associate Dean for Research in the School of Dentistry department at Marquette University

MESH terms used to index this publication - Major topics in bold

Absorbable Implants
Animals
Bone Morphogenetic Protein 2
Bone Resorption
Disease Models, Animal
Dose-Response Relationship, Drug
Female
Femur
Fracture Healing
Humans
Osteoclasts
Recombinant Proteins
Sheep
Tomography, X-Ray Computed