Experimental Spinal Fusion With Use of Recombinant Human Bone Morphogenetic Protein 2

Itoh, Hidehiro; Ebara, Sohei; Kamimura, Mikio; Tateiwa, Yutaka; Kinoshita, Tetsuya; Yuzawa, Yukio; Takaoka, Kunio

doi:10.1097/00007632-199907150-00003

Cited by 70 publications

(47 citation statements)

References 19 publications

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“…3,4,[11][12][13] Namikawa et al used b-tricalcium phosphate and PLA-DX-PEG polymer gel as a carrier and successfully reduced rhBMP-2 doses to 15-30 mg to achieve solid spine fusion in the rabbit model. 14 In this study, the results showed 2.5 mg of rhBMP-2 alone using alginate sheet could not induce intertransverse bone formation.…”

Section: Discussionmentioning

confidence: 99%

Enhancement of posterolateral lumbar spine fusion using low‐dose rhBMP‐2 and cultured marrow stromal cells

Chen

et al. 2009

Journal Orthopaedic Research

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We tested the hypothesis that the dose of recombinant human bone morphogenetic protein-2 (rhBMP-2) required to induce spine fusion can be reduced by combination with mesenchymal stem cells (MSCs). Twenty-four adult rabbits underwent posterolateral intertransverse fusion at the L4-L5 level. The animals were divided into four groups based on the implant material: autologous iliac graft, Alginate-MSCs composite, Alginate-BMP-2-MSCs composite, and Alginate-BMP-2 composite. After 16 weeks, the rabbits were euthanized for radiographic examination, manual palpation, biomechanical testing, and histology. Radiographic union of 12 intertransverse fusion areas for the autogenous iliac graft, Alginate-MSCs, Alginate-BMP-2-MSCs, and Alginate-BMP-2 groups was 11, 8, 11, and 0, respectively. Moreover, manual palpation of six fusion segments in each subgroup found solid union to be 6, 1, 5, and 0, respectively. The average torques at failure of the first three groups were 2278 AE 135, 1943 AE 140, and 2334 AE 187 N-mm, respectively. The failure torque did not differ significantly between the autograft and Alginate-BMP-2-MSCs groups; both groups were significantly higher than the Alginate-MSCs group. The results indicate that MSCs delivered with in vitro cellular doses of rhBMP-2 are more osteoinductive than MSCs without rhBMP-2. In combination with MSCs, a low dose (2.5 mg) of rh-BMP-2 could enhance bone formation and posterolateral spine fusion success in the rabbit model. 1-4 However, limitations exist in related clinical applications, including the inconsistent fusion rate and the high cost associated with the high dosage required for osteoinductive factors.During the recent decade, numerous investigators have described techniques for isolating human and animal mesenchymal stem cells (MSCs) from bone marrow.5-7 Culturing MSCs with dexamethasone, ascorbic acid, and b-glycerophosphate directs the cells into the osteogenic lineage.6,7 Additionally, recombinant human bone morphogenetic proteins (rhBMP) were reported to enhance the osteogenic potency of MSCs. 8,9 Theoretically, low-dose rhBMP-2 can improve the osteogenic potency of preconditioned MSCs and can then be used to improve the success of spinal fusion.We tested the hypothesis that rhBMP-2 can enhance the osteogenic potency of preconditioned MSCs and that the dosage of rhBMP-2 to induce intertransverse spine fusion could be lower than previously required.

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Section: Discussionmentioning

confidence: 99%

Enhancement of posterolateral lumbar spine fusion using low‐dose rhBMP‐2 and cultured marrow stromal cells

Chen

et al. 2009

Journal Orthopaedic Research

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“…The advances in material engineering have led to renewed interest in osteoconductive materials and yielded materials that may function not only as traditional bone graft expanders, but also as a scaffold for bone ingrowth. To solve these problems, a variety of bone substitutes and bone tissue engineering strategies are already being used 9,22,27) . In the present study, to increase the fusion rate we applied allograft (DMB Grafton flex) together with autograft in both study groups.…”

Section: Discussionmentioning

confidence: 99%

The Effect of Risedronate on Posterior Lateral Spinal Fusion in a Rat Model

Gezici

Ergün

Gürel

et al. 2009

J Korean Neurosurg Soc

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Objective : To evaluate the potential effects of risedronate (RIS) which shows a higher anti-resorptive effect among bisphosphonates, after a posterolateral lumbar intertransverse process spinal fusion using both autograft and allograft in a rat model. Methods : A totoal of 28 Sprague-Dawley rats were randomized into 2 study groups. A posterolateral lumbar intertransverse process spinal fusion was peformed using both autograft and allograft in a rat model. Group I (control) received 0.1 mL of steril saline (placebo) and Group II (treatment) received risedronate, equivalent to human dose (10 µg/kg/week) for 10-weeks period.Results : The fusion rates as determined by manual palpation were 69% in the group I and 46% in the group II (p = 0.251). According to radiographic score, the spinal segment was considered to be fused radiographically in 7 (53%) of the 13 controls and 9 (69%) of the 13 rats treated with RIS (p = 0.851). The mean histological scores were 5.69 ± 0.13 and 3.84 ± 0.43 for the control and treatment groups, respectively. There was a significant difference between the both groups (p = 0.001). The mean bone density of the fusion masses was 86.9 ± 2.34 in the control group and 106.0 ± 3.54 in the RIS treatment group. There was a statistical difference in mean bone densities of the fusion masses comparing the two groups (p = 0.001). Conclusion : In this study, risedronate appears to delay bone fusion in a rat model. This occurs as a result of uncoupling the balanced osteoclastic and osteoblastic activity inherent to bone healing. These findings suggest that a discontinuation of risedronate postoperatively during acute fusion period may be warranted.

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“…Many research groups are currently using this model [2,4,7,8,15]. Although the biomechanical properties of the fusion mass itself have been studied, the baseline and subsequent alterations in physiologic lumbar spine motion have not yet been established.…”

Section: Discussionmentioning

confidence: 99%

Biomechanical evaluation of the New Zealand white rabbit lumbar spine: a physiologic characterization

Grauer¹,

Erulkar²,

Patel³

et al. 2000

European Spine Journal

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IntroductionThere are many variables that affect the results of lumbar fusions. Particularly with the advent of novel methods of instrumentation and the purification of bone-stimulating growth factors, the orthopedic surgeon is faced with many surgical options. Objective comparison of these many variables is imperative. Not only must existing fusion modalities be critically evaluated, but novel modalities must also be compared to those already in use.Outcome studies are an ideal way to compare the efficacy of fusions. However, it is difficult to normalize study groups in this type of clinical trial. Furthermore, baseline Abstract Physiologic motions of the human, sheep, and calf lumbar spines have been well characterized. The size, cost, and ease of care all make the rabbit an attractive alternative choice for an animal lumbar spine model. However, comparisons of normal biomechanical characteristics of the rabbit lumbar spine have not been made to the spines of larger species. The purpose of this study was to establish baseline physiologic kinematic data for the rabbit lumbar spine. Ten skeletally mature New Zealand white rabbit osteoligamentous spines were obtained. L4-L7 spine segments were harvested and mounted. Multi-directional flexibility testing was performed by applying pure moments up to 0.27 Nm. Resulting rotations were measured using an Optotrak system. Data were analyzed for each intervertebral level in the three planes of rotation. The three levels tested had roughly similar range of motion (ROM). The mean (SD) angular ROMs in flexion for L4-L5, L5-L6, L6-L7 were 12.10°(2.59°), 12.38°(2.70°), and 15.17°(3.22°), respectively. The ROMs in extension were 5.86°(

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Experimental Spinal Fusion With Use of Recombinant Human Bone Morphogenetic Protein 2

Cited by 70 publications

References 19 publications

Enhancement of posterolateral lumbar spine fusion using low‐dose rhBMP‐2 and cultured marrow stromal cells

Enhancement of posterolateral lumbar spine fusion using low‐dose rhBMP‐2 and cultured marrow stromal cells

The Effect of Risedronate on Posterior Lateral Spinal Fusion in a Rat Model

Biomechanical evaluation of the New Zealand white rabbit lumbar spine: a physiologic characterization

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