Early-term and Mid-term Histologic Events During Single-level Posterolateral Intertransverse Process Fusion With rhBMP-2/Collagen Carrier and a Ceramic Bulking Agent In a Nonhuman Primate Model: Implications for Bone Graft Preparation

Document Type




Format of Original

8 p.

Publication Date



Lippincott Williams & Wilkins, Inc.

Source Publication

Journal of Spinal Disorders & Techniques

Source ISSN


Original Item ID

doi: 10.1097/BSD.0b013e3182767c67


Study Design: We used a non-human primate lumbar intertransverse process arthrodesis model to evaluate biological cascade of bone formation using different carrier preparation methods with a single dose of recombinant human bone morphogenetic protein-2 (rhBMP-2) at early time points.

Objective: To examine early/mid-term descriptive histological and computerized tomographic events in single-level uninstrumented posterolateral non-human primate spinal fusions using rhBMP-2/ACS combined with ceramic bulking agents in three different configurations.

Summary of Background Data: rhBMP-2 on an absorbable collagen sponge carrier (ACS) alone leads to consistent posterolateral lumbar spine fusions in lower-order animals; however, these results have been difficult to replicate in non-human primates.

Methods: Twelve skeletally mature, rhesus macaque monkeys underwent single-level posterolateral arthrodesis at L4-L5. A hydroxyapatite (HA)/tricalcium phosphate ([beta]-TCP) ceramic bulking agent in three formulations was used in the treatment groups (n=3). When used, rhBMP-2/ACS at 1.5[medium shade]mg/cc (3.0[medium shade]mg rhBMP-2) was combined with 2.5[medium shade]cc of ceramic bulking agent per side. Animals were killed at 4 weeks and 12 weeks postoperative. Computerized tomography scans were performed immediately post-op and every 4 weeks until sacrifice. Sagittal histologic sections were evaluated for bone histogenesis and location, cellular infiltration of the graft/substitute, and bone remodeling activity.

Results: Significant histological differences in the developing fusion appeared between the three rhBMP-2/ACS treatment groups at 4 and 12 weeks. At 4 weeks, bone formation appeared to originate at the transverse process and the intertransverse membrane. Cellular infiltration was greatest in granular ceramic groups compared with matrix ceramic group. Minimal to no residual ACS was identified at the early time point. At 12 weeks, marked ceramic remodeling was observed with continued bone formation noted in all carrier groups.

Conclusions: At the early time period, histology showed that bone formation appeared to originate at the transverse processes and the intertransverse membrane, indicating that the dorsal muscle bed may not be the only location for bone formation. Histology also showed that the collagen carrier for rhBMP-2 is mostly resorbed by 4 weeks. Our results as well as previous literature indicate that ceramic bulking agents are needed to provide resistance to compression caused by paraspinal muscles on the fusion bed in the posterolateral environment. Histology showed that ceramic bulking agents may offer long-term scaffolding as well as a structure to supporting bone formation of the developing fusion mass.


Journal of Spinal Disorders & Techniques, Vol. 27, No. 4 (June 2014): 212-219. DOI.