Recombinant Human Bone Morphogenetic Protein 7 Exerts Osteo-Catabolic Effects on Bone Grafts That Outweigh Its Osteo-Anabolic Capacity

This study aimed to investigate the effects of recombinant human bone morphogenetic protein (rhBMP-7) on human cancellous bone grafts (BGs) while differentiating between anabolic and catabolic events. Human BGs alone or supplemented with rhBMP-7 were harvested 14  weeks after subcutaneous implantation into NOD/Scid mice, and studied via micro-CT, histomorphometry, immunohistochemistry and flow cytometry. Immunohistochemical staining for human-specific proteins made it possible to differentiate between grafted human bone and newly formed murine bone. Only BG s implanted with rhBMP-7 formed an ossicle containing a functional hematopoietic compartment. The total ossicle volume in the BMP+ group was higher than in the BMP− group (835  mm3 vs. 365  mm3, respectively,p <  0.001). The BMP+ group showed larger BM spaces (0.47  mm vs. 0.28 mm,p = 0.002) and lower bone volume-to-total volume ratio (31% vs. 47%,p = 0.002). Immunohistochemical staining for human-specific proteins confirmed a higher ratio of newly formed bone area (murine) to total area (0.12 vs. 0.001,p <  0.001) in the BMP+ group, while the ratio of grafted bone (human) area to total area was smaller (0.14 vs. 0.34,p = 0.004). The results demonstrate that rhBMP-7 induces BG resorption at a higher rate than new bone formation while creating a haematopoietic niche. Clinicians therefore need to consider the net catabolic effect when rhBMP-7 is used with BGs. Overall, this model indicates ...
Source: Calcified Tissue International - Category: Orthopaedics Source Type: research