Effectiveness and Feasibility of Injectable Escherichia coli-Derived Recombinant Human Bone Morphogenetic Protein-2 for Anterior Lumbar Interbody Fusion at the Lumbosacral Junction in Adult Spinal Deformity Surgery: A Clinical Pilot Study

Abstract

Objective: To explore the effectiveness and feasibility of injectable Escherichia coli-derived recombinant human bone morphogenetic protein-2 (injectable E-rhBMP-2, a combination of E. coli-derived recombinant human bone morphogenic protein-2 and a hydrogel type beta-tricalcium phosphate carrier) as a bone substitute for anterior lumbar interbody fusion (ALIF) of the lumbosacral junction in adult spinal deformity (ASD) patients.

Methods: A prospective single-institution therapeutic exploratory trial was conducted. Twenty patients (average age: 69.1 years; 19 female and one male; average fusion level: 7.95) diagnosed with ASD with sagittal imbalance who underwent surgical treatment including ALIF at the lumbosacral junction from December 2017 to January 2019 were evaluated. Injectable E-rhBMP-2 was prepared by dissolving 3 mg of E. coli-derived recombinant human bone morphogenetic protein-2 in 1.5 ml H₂ O and mixing in situ with 9 g hydrogel type beta-tricalcium phosphate. This bone graft substitute was loaded onto a metal ALIF cage and L₅ -S₁ ALIF was performed in routine manner. Then posterior column osteotomy with multilevel oblique lumbar interbody fusion or pedicle subtraction osteotomy with accessory rod technique was performed to restore sagittal balance. Patients were followed up for 12 months. CT-based fusion rates were examined at 6 and 12 months after surgery. Also, clinical outcomes (Oswestry Disability Index [ODI], Visual Analog Scale [VAS] score of the back and leg) were evaluated at 6 and 12 months after surgery. All postoperative adverse events were evaluated for the association with injectable E.BMP-2.

Results: Of the 20 patients, loss to follow-up occurred with one patient at 6 months after surgery and one patient at 12 months after surgery, resulting in a total of 18 patients who were available for follow-up. Six months after surgery, 68.4% patients achieved solid fusion. Twelve months after surgery, 100% fusion rate was achieved. Compared to baseline values, ODI scores improved to 45.8% and 63.7%, VAS (back) improved to 69.2% and 72.8%, and VAS (leg) improved to 49.2% and 64.8%, respectively, at 6 and 12 months after surgery (p < 0.001 for all). Ten cases of adverse events occurred. But no adverse events were associated with injectable E-rhBMP-2.

Conclusion: Injectable E-rhBMP-2 will be an effective bone graft substitute when achieving solid interbody fusion in the lumbosacral junction.

Keywords: adult spinal deformity; anterior lumbar interbody fusion; beta-tricalcium phosphate; bone morphogenetic protein; lumbosacral junction.

Fig. 1

Injectable Escherichia coli‐derived recombinant human bone morphogenic protein‐2 (E.BMP‐2)‐loaded beta‐tricalcium phosphate (β‐TCP) hydrogel. (A) 3 mg E.BMP‐2 was dissolved in 1.5 ml H₂O. (B) 9 g hydrogel type β‐TCP was used. (C) A and B were mixed in situ. (D) The final bone graft substitute (NOVOSIS Inject) was loaded onto an anterior lumbar interbody fusion (ALIF) cage

Fig. 2

(A) A 67‐year‐old women presented to us with degenerative lumbar kyphosis with sagittal imbalance (SVA 166mm, TK 6°, LL −7°, PT 29°, SS 21° and PI 50°). There was bony ankylosis was at L₄₋₅. (B) We performed ALIF on L₅–S₁ with NOVOSIS Inject, OLIF on L₂₋₄, and posterior column osteotomy from T₁₀ to S₁ with sacropelvic fixation. Optimal sagittal alignment was maintained until 12 months after surgery (SVA 3 mm, TK 26°, LL −62°, PT 9°, SS 41°). (C) Immediate postoperative state of lumbosacral junction with NOVISIS Inject loaded onto an ALIF cage. (D) Six months after surgery, bridging between the endplates was on progression. (E,F) Twelve months after surgery, grade 4 solid fusion was achieved. Abbreviations: ALIF, anterior lumbar interbody fusion; LL, lumbar lordosis; OLIF, oblique lumbar interbody fusion; PI, pelvic incidence; PT, pelvic tilt; SS, sacral slope; SVA, sagittal vertical axis; TK, thoracic kyphosis