The in vivo biological effects of intradiscal recombinant human bone morphogenetic protein-2 on the injured intervertebral disc: an animal experiment.
METHODS
Prospective analysis.


OBJECTIVE
To investigate biologic influences of recombinant human bone morphogenetic protein (rhBMP)-2 on intervertebral discs after anular tears.


BACKGROUND
Treatments for intervertebral disc injury or degeneration are unsatisfactory. rhBMP-2, a high-potency osteoinductive and chondroinductive substance, is approved for use in anterior lumbar interbody fusions. rhBMP-2 stimulates the proliferation of rat disc cells and the secretion of extracellular matrix in vitro. In vivo responses in the intervertebral disc after anular tears are rarely studied.


METHODS
Twenty New Zealand white rabbits received full-thickness anular tears and intradiscal injections of saline (control) and rhBMP-2 0.1 mg with and without coral grafts at L2-L3, L3-L4, and L4-L5, respectively. Three died or had infection. Therefore, 17 underwent radiography and sacrifice at 12 weeks. Spinal sections were stained with hematoxylin and eosin to examine responses to rhBMP-2.


RESULTS
Radiographs revealed degenerative changes, such as disc space narrowing and irregularity, subchondral sclerosis, osteophyte formation, and hypertrophy of vertebral endplates in all groups. Degeneration was more frequent and severe with rhBMP-2 with (P < 0.01) and without (P < 0.05) coral than with saline. Two rabbits receiving rhBMP-2 and coral achieved solid interbody bony fusion. New bone formation was noted in 2 controls, in 3 animals treated with rhBMP-2, and in 4 treated with rhBMP-2 and coral. Vascularity and fibroblast proliferation increased with rhBMP-2 (n = 14) and rhBMP-2 with coral (n = 9) compared with control (n = 3; P < 0.01 and P = 0.03, respectively). Inflammatory infiltrates increased with rhBMP-2 (n = 8) compared with control (n = 2; P = 0.03).


CONCLUSIONS
Degenerative changes were more frequent and severe in the groups treated with rhBMP-2 with or without coral in radiographic findings. In histopathologic findings, rhBMP-2 promoted hypervascularity and fibroblast proliferation of the intervertebral disc after an anular tear.
Huang
Kuo-Yuan
KY
Department of Orthopedics and Institute of Clinical Medicine, National Cheng Kung University Medical Center, Tainan, Taiwan.
Yan
Jing-Jou
JJ
Hsieh
Chin-Chiang
CC
Chang
Ming-Shi
MS
Lin
Ruey-Mo
RM
D000818:Animals; D037421:Anthozoa; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000008:administration & dosage / Q000494:pharmacology*; D018786:Bone Substitutes / Q000627:therapeutic use; D049109:Cell Proliferation / Q000187:drug effects; D004195:Disease Models, Animal; D005347:Fibroblasts / Q000187:drug effects / Q000473:pathology; D006801:Humans; D007278:Injections, Spinal; D007403:Intervertebral Disc / Q000098:blood supply / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology / Q000601:surgery; D008159:Lumbar Vertebrae; D008297:Male; D018919:Neovascularization, Physiologic / Q000187:drug effects; D016348:Osseointegration / Q000187:drug effects; D011817:Rabbits; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology*; D013122:Spinal Diseases / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000008:administration & dosage / Q000494:pharmacology*
D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D018786:Bone Substitutes; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; C499469:recombinant human bone morphogenetic protein-2