Retrograde ejaculation after anterior lumbar interbody fusion with and without bone morphogenetic protein-2 augmentation: a 10-year cohort controlled study

Background context

Retrograde ejaculation (RE) is a complication of anterior lumbar interbody fusion (ALIF) techniques. Most commonly, this results from mechanical or inflammatory injury to the superior hypogastric plexus near the aortic bifurcation. Bone morphogenetic protein-2 (BMP-2) has been used in spinal fusions and has been associated with inflammatory and neuroinflammatory adverse reactions, which may contribute to RE development after anterior lumbar surgery.

Purpose

While controlling for anterior approach technique, we compared the incidence of RE with and without rhBMP-2 exposure, in large, matched cohorts of patients after ALIF.

Study design

Retrospective analysis of 10 years of prospectively gathered outcomes data on consecutive-patient cohorts having the same anterior exposure technique for ALIF with and without rhBMP-2 use.

Patient sample

All male patients without baseline sexual incapacity and having ALIF for lumbar spondylosis or spondylolisthesis of the lowest one or two lumbar levels with and without rhBMP-2, from 2002 through 2011.

Outcome measures

Diagnosis of RE as a new finding after ALIF compared against BMP-2 exposure, comorbid conditions, and other urological complications after ALIF surgery.

Methods

From the comprehensive surgical database at a high volume, university practice, male subjects having ALIF at one (L5/S1) or two levels (L4/5, L5/S1) from 2002 to 2011 were identified. Baseline comorbid factors, postoperative urinary catheter/retention events, and RE events were recorded and comparative incidence compared.

Results

There were four consecutive-patient cohorts identified: one before rhBMP-2 use was adopted (n=174), two cohorts in which BMP-2 use was routine (n=88 and n=151), and one final cohort after BMP-2 use was discontinued from routine use (n=59). The cohorts with and without BMP-2 exposure were closely comparable for age, approach, levels of surgery, comorbid factors affecting RE. Of 239 patients with ALIF and exposure to BMP-2, RE was diagnosed in 15 subjects (6.3%), compared with an RE diagnosis rate of two of 233 control patients without BMP-2 exposure (0.9%; p=.0012). Urinary retention after bladder catheter removal was also more frequently observed in patients exposed to BMP-2 (9.7%) compared with control patients (4.6%; p=.043). Of the baseline comorbid factors, medical or surgical treatment for prostatic hypertrophy disease was associated with an increased risk of RE in the BMP-2 patients (p=.034).

Conclusions

This study confirms previous reports of a higher rate of RE in ALIF procedures using rhBMP-2 and an open anterior approach to the spine. This effect may be associated with an increased risk of postoperative urinary retention after BMP-2 exposure. The magnitude of the RE effect may be increased with concomitant prostatic disease treatments.     

Nerve injury after lateral lumbar interbody fusion: a review of 919 treated levels with identification of risk factors

Background contextLateral lumbar interbody fusion (LLIF) has become an increasingly common minimally invasive procedure for selective degenerative deformity correction, reduction of low-grade spondylolisthesis, and indirect foraminal decompression. Concerns remain about the safety of the transpsoas approach to the spine due to proximity of the lumbosacral plexus.PurposeTo address risk factors for iatrogenic nerve injury in a large cohort of patients undergoing LLIF.Study designRetrospective analysis of 919 LLIF procedures to identify risk factors for lumbosacral plexus injuries.MethodsThe medical charts of patients who underwent transpsoas interbody fusion with or without supplemental posterior fusion for degenerative spinal conditions over a 6-year period were retrospectively reviewed. Patients with prior lumbar spine surgery or follow-up of less than 6 months were excluded. Factors that may affect the neurologic outcome were investigated in a subset of patients who underwent stand-alone LLIF.ResultsFour hundred fifty-one patients (males/females: 179/272) met the inclusion criteria and were followed for a mean of 15 months (range, 6–53 months). Average age at the time of surgery was 63 years (range, 24–90 years). Average body mass index was 29 kg/m² (range, 17–65 kg/m²). A total of 919 levels were treated (mean, 2 levels per patient). Immediately after surgery, 38.5% of the patients reported anterior thigh/groin pain, whereas sensory and motor deficits were recorded in 38% and 23.9% of the patients, respectively. At the last follow-up, 4.8% of the patients reported anterior thigh/groin pain, whereas sensory and motor deficits were recorded in 24.1% and 17.3% of the patients, respectively. When patients with neural deficits present before surgery were excluded, persistent surgery-related sensory and motor deficits were identified in 9.3% and 3.2% of the patients, respectively. Among 87 patients with minimum follow-up of 18 months, persistent surgery-related sensory and motor deficits were recorded in 9.6% and 2.3% of the patients, respectively. Among patients with stand-alone LLIF, the level treated was identified as a risk factor for postoperative lumbosacral plexus injury. The use of recombinant human bone morphogenetic protein 2 was associated with persistent motor deficits.ConclusionsAlthough LLIF is associated with an increased prevalence of anterior thigh/groin pain as well as motor and sensory deficits immediately after surgery, our results support that pain and neurologic deficits decrease over time. The level treated appears to be a risk factor for lumbosacral plexus injury.     

Multiple myeloma exacerbation following utilization of bone morphogenetic protein-2 in lateral lumbar interbody fusion: a case report and review of the literature

Background contextRecent studies generated antithetic results regarding the safety of bone morphogenetic protein-2 (BMP-2) use in spine surgery, and the effect of this biologic adjunct on myeloma cells remains to be fully elucidated.PurposeThe purpose of this study was to present a case of multiple myeloma (MM) exacerbation after BMP-2 implantation in the setting of lateral lumbar interbody fusion (LLIF).Study designCase report and literature review.MethodsThe medical records, laboratory findings, and radiographic imaging studies of an 86-year-old female patient with exacerbation of previously undiagnosed MM were reviewed.ResultsThe patient presented with a 10-year history of debilitating lower back pain and bilateral lower extremity claudication. Radiographic studies depicted lumbar scoliosis and lateral spondylolisthesis. Preoperative serum immunofixation electrophoresis showed a serum immunoglobulin A kappa paraprotein-peak; however, the patient had never been diagnosed with MM or reported any unexplained fever, night sweats, or weight loss indicative of MM. The patient underwent LLIF from L1–L5 supplemented by BMP-2. On postoperative day 1, the patient was evaluated by the hematology department for paraproteinemia. Serum electrophoresis showed decreased albumin, hypogammaglobulinemia, and suspicious broadening of the complement component in the beta region. Postoperative imaging studies (19 weeks) depicted progression of a previously visible intraosseous lesion, and anterior cortical breakthrough (L5), in addition to a soft tissue mass at the T10 level. Histological examination of iliac crest and T10 vertebral biopsies showed fatty marrow infiltration by plasma cells and plasma cell dyscrasia, proving the diagnosis of MM. The patient died 10 months after surgery due to complications related to a methicillin-resistant Staphylococcus aureus infection.ConclusionsBased on the present case, perhaps one should consider that in patients with abnormal electrophoresis results, even in the absence of a prior diagnosis of MM as well as in the absence of symptoms indicative of MM, BMPs should be administered only after preoperative exclusion of neoplastic disease.     

Retrospective analysis of L5–S1 axial lumbar interbody fusion (AxiaLIF): a comparison with and without the use of recombinant human bone morphogenetic protein-2

Background context

Since approval by the Food and Drug Administration in 2002, use of recombinant human bone morphogenetic protein-2 (rhBMP-2) to promote spinal fusion is increasing.

Purpose

In this comparative analysis, the authors assess fusion rates and clinical outcomes of patients who underwent a presacral axial lumbar interbody fusion (AxiaLIF) (TranS1 Inc., Wilmington, NC, USA) at L5–S1 with posterior instrumentation, with or without rhBMP-2.

Study design

Retrospective case-matched chart review.

Patient sample

A matched cohort of 99 patients underwent fusion performed by two surgeons at two institutions (2005–2007): Specifically, 45 patients at The Christ Hospital received rhBMP-2 and 54 patients at the University of Pittsburgh had no rhBMP-2.

Outcome measures

Pre- and postoperative visual analog scale (VAS) scores were recorded, as was physiologic data on fusion rates, blood loss, and length of stay. Preoperative and postoperative Oswestry Disability Index (ODI) scores were obtained for patients treated with rhBMP-2. Odom’s outcome criteria were obtained at 2-year follow-up for patients without rhBMP-2.

Methods

Data were collected prospectively. Demographic data, including sex and age, were matched.

Results

During the 2-year follow-up period, patients noted reduction in back pain and improved functional outcome measures. The most rapid reduction in VAS pain scores and improvement in ODI occurred within the first 3 months after surgery. Mean pre- and postoperative VAS scores improved 59% from 72.9 to 30.1 with rhBMP-2 and 72% from 81.3 to 22.6 without rhBMP-2. In rhBMP-2-treated patients, mean ODI scores were 54.4% preoperatively and 23.7% postoperatively, a 56.4% improvement at 2 years. In the non–rhBMP-2 patients, 80% reported excellent to good results using Odom criteria. Fusion rates were 96% with rhBMP-2 and 93% without rhBMP-2. Operative blood loss averaged 82 cm³ with and less than 50 cm³ without rhBMP-2. No differences in hospital length of stay were noted between the two groups or in the fusion rates with pedicle screws or facet screws. No major complications occurred with or without rhBMP-2.

Conclusions

In our case-matched series, clinical outcomes were similar for patients who underwent an AxiaLIF L5–S1 interbody fusion with or without rhBMP-2. The data strongly suggest that there is a high confidence for no effect on fusion rate by using rhBMP-2.     

Contralateral psoas seroma after transpsoas lumbar interbody fusion with bone morphogenetic protein-2 implantation

Background contextThe lateral transpsoas approach to interbody fusion of the lumbar spine (lateral lumbar interbody fusion [LLIF]) with recombinant human bone morphogenetic protein-2 (BMP-2) augmentation has been increasingly performed in recent years. Potential side effects and adverse sequelae of BMP-2 in the acute setting remain to be fully elucidated.PurposeTo review the literature for reports of complications related to BMP-2 implantation in lumbar spinal surgery and present a case of a contralateral psoas muscle seroma after LLIF with BMP-2 implantation.Study designCase report and literature review.MethodsThe PubMed database was searched for articles related to adverse events to BMP-2 in lumbar spinal surgery. We report the case of a 57-year-old woman who underwent routine right-sided transpsoas approach for LLIF with the use of BMP-2 at our institution and developed a left-sided psoas muscle fluid accumulation 2 weeks postoperatively.ResultsNo reports of complications contralateral to an LLIF approach attributable to an inflammatory response to BMP-2 were identified in the English literature. In the presented patient, a large (4.2×6.5×2.7 cm) left-sided sterile intramuscular psoas fluid collection was seen on a magnetic resonance imaging study obtained on postoperative day 14. At a 6-month follow-up, left-sided L5 radiculopathy resulting in 4/5 foot drop was confirmed by electromyography. The patient reported here represents the only case of a contralateral psoas seroma with suspected association to BMP-2 utilization in LLIF encountered at our institution.ConclusionsA serous psoas muscle fluid accumulation after BMP-2 implantation may rarely occur contralateral to the surgical approach for LLIF. Further characterization of complications related to BMP-2 implantation after lumbar spinal surgery will help guide preoperative informed decision making and the management of this unusual postoperative adverse event.     

Clinical sequelae after rhBMP-2 use in a minimally invasive transforaminal lumbar interbody fusion

Background contextRecent reports of postoperative radiculitis, bone osteolysis, and symptomatic ectopic bone formation after recombinant human bone morphogenetic protein-2 (rhBMP-2) use in transforaminal lumbar interbody fusions (TLIFs) are a cause for concern.PurposeTo determine the clinical and radiographic complications associated with BMP utilization in a minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) environment.Study design/settingRetrospective clinical case series at a single institution.Patient sampleFive hundred seventy-three consecutive patients undergoing an MIS-TLIF.Outcome measuresReoperation rates and total costs associated with complications of rhBMP-2 use and pseudarthrosis.MethodsA retrospective review of 610 consecutive patients undergoing an MIS-TLIF (2007–2010) by a single surgeon at our institution was performed (mean age 48.7 years, range 26–82 years). All patients underwent an MIS laminectomy with bilateral facetectomy, single TLIF cage, unilateral pedicle screw fixation, and 12 mg (large kit) or 4.2 mg (small kit) of rhBMP-2. The BMP-2 collagen-soaked sponge was placed anteriorly in the disc space, followed by local bone graft, and then the cage was filled only with local bone and no BMP-2. Patients were evaluated at 6 months and 1 year with computed tomography (CT) scan. Those demonstrating neuroforaminal bone growth, osteolysis/cage migration, or pseudarthrosis were reviewed, and cost data including direct cost/procedure for both index and revision surgeries were collected.ResultsOf the 573 patients, 10 (1.7%) underwent 15 additional procedures based on recalcitrant radiculopathy and CT evidence of neuroforaminal bone growth, vertebral body osteolysis, and/or cage migration. Thirty-nine patients (6.8%) underwent reoperation for clinically symptomatic pseudarthrosis. Bone overgrowth was associated with nerve impingement and radiculopathy in all 10 patients (small kit, n=9; large kit, n=1). Osteolysis and cage migration occurred in 2 (20%) of these same 10 patients. Average total costs were calculated per procedure ($19,224), and the costs for reoperation equaled $14,785 per encounter for neuroforaminal bone growth and $20,267 for pseudarthrosis.ConclusionsSymptomatic ectopic bone formation, vertebral osteolysis, and pseudarthrosis are recognized complications with the use of rhBMP-2 in MIS-TLIFs. Potential causes include improper dosage and a closed space that prevents the egress of the postoperative BMP-2 fluid collection. Management of these complications has a substantial cost for the patient and the surgeon and needs to be considered with the off-label use of rhBMP-2.     

重组人骨形态发生蛋白-2对鼠雪旺细胞增殖及生长相关蛋白GAP-43表达的影响

目的 观察重组入骨形态发生蛋白-2( rhBMP-2)对体外培养的乳鼠雪旺细胞增殖及生长相关蛋白( GAP-43)表达的影响。方法 将纯化的雪旺细胞分两组,一组设为对照,另一种加含终质量浓度为5 μg/L rhBMP-2的DMEM/F12培养液培养,在培养后0、12、24、36、48、72 h分别用噻唑蓝(MTT)比色法检测不同时间点的A值并绘制生长曲线;用BrdU法测定雪旺细胞增殖率;用Western blot法检测GAP-43蛋白的表达水平。结果 经含5μg/L rhBMP-2培养液培养的雪旺细胞,在24、36、48 h细胞增殖率明显高于对照组,差异有统计学意义(P＜0.05);实验组中GAP-43在24、36、48 h的表达也显著高于对照组(P＜0.05)。结论 rhBMP-2有促进雪旺细胞分裂增殖和GAP-43蛋白表达的作用,可能是其促进周围神经再生的重要机制之一。     

Nitric oxide modulates recombinant human bone morphogenetic protein-2-induced corticocancellous autograft incorporation: a study in rat intertransverse fusion

A novel rat model was used to investigate the effect of nitric oxide synthase inhibition in posterior spinal fusion augmented with recombinant human bone morphogenetic protein-2. Nitric oxide (NO) has important physiological functions including the modulation of fracture healing. Recombinant human BMP-2 (rhBMP-2) enhances spinal fusion. It is not known whether nitric oxide has a role in rhBMP-2 enhanced spinal fusion and remodeling. A novel rat intertransverse fusion model was created using a defined volume of bone graft along with a collagen sponge carrier, which was compacted and delivered using a custom jig. The control groups consisted of a sham group (S, n = 20), an autograft + carrier group (A, n = 28) and a group consisting of 43 μg of rhBMP-2 mixed with autograft + carrier (AB, n = 28). Two experimental groups received a nitric oxide synthase (NOS) inhibitor, N ^G-nitro l-arginine methyl ester, in a dose of 1 mg/ml ad lib in the drinking water (AL, n = 28) and one of these experimental groups had rhBMP-2 added to the graft mixture at the time of surgery (ALB, n = 28). Rats were killed at 22 and 44 days, spinal columns subjected to radiology, biomechanics and histology. On a radiographic score (0–4) indicating progressive maturation of bone fusion mass, no difference was found between the A and AL groups, however, there was a significant enhancement of fusion when rhBMP-2 was added when compared to the A group (P < 0.001). However, on day 44, the ALB group showed significantly less fusion progression when compared to the AB group (P < 0.01). There was a 25% (P < 0.05) more fusion-mass-area in day 44 of ALB group when compared to day 44 of the AB group indicating that NOS inhibition delayed the remodeling of the fusion mass. Biomechanically, the rhBMP-2 groups were stiffer at all time points compared to the NOS inhibited groups. Decalcified histology demonstrated that there was a delay in graft incorporation whenever NOS was inhibited (AL and ALB groups) as assessed by a 5 point histological maturation score. In a novel model of rat intertransverse process fusion, nitric oxide synthase modulates rhBMP-2 induced corticocancellous autograft incorporation.     

Relationship of the lumbar plexus branches to the lumbar spine: anatomical study with application to lateral approaches

Background Context

Injuries to the lumbar plexus during lateral approaches to the spine are not uncommon and may result in permanent deficits. However, the literature contains few studies that provide landmarks for avoiding the branches of the lumbar plexus.

Neuroforaminal chondrocyte metaplasia and clustering associated with recombinant bone morphogenetic protein-2 usage in transforaminal lumbar interbody fusion

Background contextRecombinant human bone morphogenetic protein-2 (rhBMP-2) is commonly used to augment posterior and interbody spinal fusion techniques and has many reported side effects. Neuroforaminal heterotopic ossification (HO) is a known cause of postoperative leg pain, but the pathohistologic composition of this material is not well understood.PurposeThe purpose of this article was to report the histologic composition of a case of HO and lumbar radiculopathy after transforaminal lumbar interbody fusion with rhBMP-2.Study design/settingThis is a case report.Patient sampleThis is a single patient case report.Outcome measuresThe outcomes considered were physician-recorded clinical, physiological, and functional measures.MethodsA retrospective review of a single patient was performed. Clinical, radiographic, and pathologic specimens were reviewed and are reported.ResultsA 69-year-old woman presented with low back pain and right leg radicular pain associated with L4–L5 stenosis and a recurrent facet cyst. After attempted nonsurgical care, she underwent an L4–L5 revision decompression with interbody and posterolateral fusions including off-label rhBMP-2. Postoperatively, her symptoms resolved for approximately 7 months but then returned in association with right L4–L5 foraminal HO. The ectopic tissue was notably larger than suggested by preoperative computed tomographic scan. It was decompressed, which then improved her symptoms. Histologic examination of the specimen revealed three discrete tissue types: a nonspecific fibrovascular stroma; immature osteoid and woven bone; and chondrocyte metaplasia with chondrocyte clustering.ConclusionsNeuroforaminal HO formation is a reported side effect associated with the off-label use of rhBMP-2 for posterior lumbar interbody fusion. The mechanism of formation and the composition of this material are not well understood but may involve a chondrocyte differentiation pathway.     

Effect of bone morphogenetic protein-7 transfected bone marrow mesenchymal stem cells on renal injury in rats with chronic renal failure

Objective To observe the bone marrow mesenchymal stem cells (BMSCs) modified by bone morphogenetic protein-7 (BMP-7) gene on the expression of renal BMP-7, transforming growth factor-β1 (TGF-β1) and vascular endothelial growth factor (VEGF), further to explore its protective mechanism on renal injury in rats with chronic renal failure (CRF). Methods BMSCs with high expression of BMP-7 gene (BMSCs-BMP-7) and empty vector-BMSCs (BMSCs-EV) were obtained by lentiviral-mediated gene transfection. Thirty male Sprague-Dawley (SD) rats were randomly divided into 5 groups, 6 in each group: normal control (CON) group; PBS intervention (CRF with PBS infusion, CRF+PBS) group; BMSCs intervention (CRF with BMSCs infusion, CRF+BMSCs) group; BMSCs-EV intervention (CRF with BMSCs-empty vector infusion, CRF+BMSCs-EV) group and BMSCs-BMP-7 intervention (CRF with BMSCs-BMP-7 infusion, CRF+BMSCs-BMP-7) group. The CRF model was established by 5/6 nephrectomy. The CON group was a sham operation group. The corresponding 12-weeks interventions of each experimental group were performed after 2 weeks of modeling, the rats in the CON group and the CRF+PBS group were injected with 1 ml of PBS through the tail vein, and the other three groups were injected with 1 ml of the corresponding cell suspension once a week. At the time of sacrifice, blood and renal tissue samples were reserved. Serum creatinine (Scr) and blood urea nitrogen (BUN) were measured by routine biochemical methods, and the expression of BMP-7, VEGF, TGF-β1 in kidney was assayed by Western blotting. Results At the time of sacrifice, the levels of Scr and BUN in the CRF+PBS group were significantly higher than those in the CON group (all P＜0.01); Compared with the CRF+PBS group, the Scr and BUN of the CRF+BMSCs group, CRF+BMSCs-EV group and CRF+BMSCs-BMP-7 group were decreased to different extents, the differences were statistically significant (all P＜0.01); the Scr and BUN of the CRF+BMSCs-BMP-7 group were significantly lower than CRF+BMSCs group and CRF+BMSCs-EV group (all P＜0.05). The expression of BMP-7 and VEGF were the lowest in the CRF+PBS group. Compared with the CRF+PBS group, the expression of BMP-7 and VEGF in the CRF+BMSCs group, CRF+BMSCs-EV group and CRF+BMSCs-BMP-7 group were significantly increased respectively (all P＜0.05). The expression of the BMP-7 and VEGF in the CRF+BMSCs-BMP-7 group were higher than those in the CRF+BMSCs group and CRF+BMSCs-EV group (P＜0.01). Compared with the CON group, the expression of TGF-β1 in the CRF+PBS group was significantly increased (P＜0.01); compared with the CRF+PBS group, the expression of TGF-β1 in the CRF+BMSCs group, CRF+BMSCs-EV and CRF+BMSCs-BMP-7 group was significantly decreased (all P＜0.01); the expression of TGF-β1 in the CRF+BMSCs-BMP-7 group was lower than the CRF+BMSCs and CRF+BMSCs-EV group (both P＜0.01). Conclusions BMSCs modified by BMP-7 has a protective effect on CRF rats; its protective mechanism may be related to antagonizing TGF-β1 and up-regulation of renal VEGF expression.     

Fusion and subsidence rate of stand alone anterior lumbar interbody fusion using PEEK cage with recombinant human bone morphogenetic protein-2

Introduction

Anterior lumbar interbody fusion (ALIF) is an established treatment for structural instability associated with symptomatic disk degeneration (SDD). Stand-alone ALIF offers many advantages, however, it may increase the risk of non-union. Recombinant human bone morphogenetic protein-2 (BMP-2) may enhance fusion rate but is associated with postoperative complication. The optimal dose of BMP-2 remains unclear. This study assessed the fusion and subsidence rates of stand-alone ALIF using the SynFix-LR interbody cage with 6 ml/level of BMP-2.

Methods

Thirty-two ALIF procedures were performed by a single surgeon in 25 patients. Twenty-five procedures were performed for SDD without spondylolisthesis (SDD group) and seven procedures were performed for SDD with grade-I olisthesis (SDD-olisthesis group). Patients were followed-up for a mean of 17 ± 6 months.

Results

Solid fusion was achieved in 29 cases (90.6 %) within 6 months postoperatively. Five cases of implant subsidence were observed (16 %). Four of these occurred in the SDD-olisthesis group and one occurred in the SDD group (57 % vs. 4 % respectively; p = 0.004). Three cases of subsidence failed to fuse and required revision. The body mass index of patients with olisthesis who developed subsidence was higher than those who did not develop subsidence (29 ± 2.6 vs. 22 ± 6.5 respectively; p = 0.04). No BMP-2 related complications occurred.

Conclusion

The overall fusion rate of stand-alone ALIF using the SynFix-LR system with BMP-2 was 90.6 %, comparable with other published series. No BMP-2 related complication occurred at a dose of 6 mg/level. Degenerative spondylolisthesis and obesity seemed to increase the rate of implant subsidence, and thus we believe that adding posterior fusion for these cases should be considered.     

人重组骨形态发生蛋白-2修复全层关节软骨缺损的实验研究

目的 :研究人重组骨形态发生蛋白 2 (rhBMP 2 )对全层关节软骨缺损的修复 ,观察修复效果。方法 :家犬 8只 (16膝 ) ,每个膝内外髁均做全层软骨缺损 ,内外髁共 3 2个缺损。随机分为 4组 ,每组 2只。每只犬一侧关节行胶原海绵吸附rh BMP填充内外髁缺损 ,另一侧以单纯胶原海绵填充作对照 ,不处理组为空白对照。术后 2、4、 8、 12周取材作大体、光镜、透射电镜观察。结果 :rh BMP组为类软骨细胞修复 ,而单纯胶原海绵组和空白组均为纤维性修复。结论 :rhBMP 2有效地促进关节软骨缺损的修复 ,可以作为临床上治疗关节软骨缺损的方法     

Efficacy of Escherichia coli-derived recombinant human bone morphogenetic protein-2 in posterolateral lumbar fusion: an open,active-controlled,randomized, multicenter trial

Background Context

The efficacy and safety of recombinant human bone morphogenetic protein-2 (rhBMP-2) as a bone graft substitute in spinal fusion has been widely researched. However, no study of the efficacy and safety of Escherichia coli-derived rhBMP-2 (E.BMP-2) with a hydroxyapatite (HA) carrier has been proposed.

丝素蛋白增强型磷酸钙复合rhBMP-2用于绵羊腰椎椎体间融合的实验研究

目的 评价可注射丝素蛋白增强型磷酸钙(silk fibroin/calcium phosphate cement,SF/CPC)复合人重组骨形态发生蛋白-2(recombinant human bone morphogenetic protein-2,rhBMP-2)应用于绵羊腰椎椎体间融合的效果.方法 24只绵羊均建立L1.2、L3.4和L5.6前路椎体间融合模型.每只绵羊的3个腰椎间隙随机植入SF/CPC、CPC/rhBMP-2、SF/CPC/rhBMP-2和自体髂骨中的3种.分别于术后6个月和12个月各处死12只绵羊.每个时段均获得36个腰椎手术节段,每种材料9个节段.通过大体观察、手触检测、CT扫描、非破坏性生物力学测试和组织学观察分析脊柱融合状况.结果 术后6个月时,手触检测SF/CPC、CPC/rhBMP-2、SF/CPC/rhBMP-2以及髂骨的融合率分别为0、33.33%(3/9)、55.56%(5/9)和77.78%(7/9);12个月时为11.11%(1/9)、44.44%(4/9)、77.78%(7/9)和77.78%(7/9).生物力学显示6个月时,前屈、后伸、左屈和右屈的融合刚度:髂骨＞SF/CPC/rhBMP-2＞CPC/rhBMP-2＞SF/CPC;12个月时SF/CPC/rhBMP-2刚度与髂骨相近,SF/CPC最小.组织学定量表明:6个月时,髂骨新生骨量＞SF/CPC/rhBMP-2＞CPC/rhBMP-2＞SF/CPC;而钙磷残留量依次增多;12个月时,SF/CPC/rhBMP-2新生骨量与髂骨相近;SF/CPC最少;钙磷残留量依次增多.结论 SF/CPC/rhBMP-2人工骨具有骨传导和骨诱导性,降解与成骨能力匹配,是一种理想的脊柱融合材料.     

丝素蛋白增强型磷酸钙复合rhBMP-2用于绵羊腰椎椎体间融合的实验研究

目的 评价可注射丝素蛋白增强型磷酸钙(silk fibroin/calcium phosphate cement,SF/CPC)复合人重组骨形态发生蛋白-2(recombinant human bone morphogenetic protein-2,rhBMP-2)应用于绵羊腰椎椎体间融合的效果.方法 24只绵羊均建立L1.2、L3.4和L5.6前路椎体间融合模型.每只绵羊的3个腰椎间隙随机植入SF/CPC、CPC/rhBMP-2、SF/CPC/rhBMP-2和自体髂骨中的3种.分别于术后6个月和12个月各处死12只绵羊.每个时段均获得36个腰椎手术节段,每种材料9个节段.通过大体观察、手触检测、CT扫描、非破坏性生物力学测试和组织学观察分析脊柱融合状况.结果 术后6个月时,手触检测SF/CPC、CPC/rhBMP-2、SF/CPC/rhBMP-2以及髂骨的融合率分别为0、33.33%(3/9)、55.56%(5/9)和77.78%(7/9);12个月时为11.11%(1/9)、44.44%(4/9)、77.78%(7/9)和77.78%(7/9).生物力学显示6个月时,前屈、后伸、左屈和右屈的融合刚度:髂骨＞SF/CPC/rhBMP-2＞CPC/rhBMP-2＞SF/CPC;12个月时SF/CPC/rhBMP-2刚度与髂骨相近,SF/CPC最小.组织学定量表明:6个月时,髂骨新生骨量＞SF/CPC/rhBMP-2＞CPC/rhBMP-2＞SF/CPC;而钙磷残留量依次增多;12个月时,SF/CPC/rhBMP-2新生骨量与髂骨相近;SF/CPC最少;钙磷残留量依次增多.结论 SF/CPC/rhBMP-2人工骨具有骨传导和骨诱导性,降解与成骨能力匹配,是一种理想的脊柱融合材料.     

丝素蛋白增强型磷酸钙复合rhBMP-2用于绵羊腰椎椎体间融合的实验研究

目的 评价可注射丝素蛋白增强型磷酸钙(silk fibroin/calcium phosphate cement,SF/CPC)复合人重组骨形态发生蛋白-2(recombinant human bone morphogenetic protein-2,rhBMP-2)应用于绵羊腰椎椎体间融合的效果.方法 24只绵羊均建立L1.2、L3.4和L5.6前路椎体间融合模型.每只绵羊的3个腰椎间隙随机植入SF/CPC、CPC/rhBMP-2、SF/CPC/rhBMP-2和自体髂骨中的3种.分别于术后6个月和12个月各处死12只绵羊.每个时段均获得36个腰椎手术节段,每种材料9个节段.通过大体观察、手触检测、CT扫描、非破坏性生物力学测试和组织学观察分析脊柱融合状况.结果 术后6个月时,手触检测SF/CPC、CPC/rhBMP-2、SF/CPC/rhBMP-2以及髂骨的融合率分别为0、33.33%(3/9)、55.56%(5/9)和77.78%(7/9);12个月时为11.11%(1/9)、44.44%(4/9)、77.78%(7/9)和77.78%(7/9).生物力学显示6个月时,前屈、后伸、左屈和右屈的融合刚度:髂骨＞SF/CPC/rhBMP-2＞CPC/rhBMP-2＞SF/CPC;12个月时SF/CPC/rhBMP-2刚度与髂骨相近,SF/CPC最小.组织学定量表明:6个月时,髂骨新生骨量＞SF/CPC/rhBMP-2＞CPC/rhBMP-2＞SF/CPC;而钙磷残留量依次增多;12个月时,SF/CPC/rhBMP-2新生骨量与髂骨相近;SF/CPC最少;钙磷残留量依次增多.结论 SF/CPC/rhBMP-2人工骨具有骨传导和骨诱导性,降解与成骨能力匹配,是一种理想的脊柱融合材料.     

Vertebral osteolysis after posterior interbody lumbar fusion with recombinant human bone morphogenetic protein 2: a report of five cases.

BACKGROUND: Recombinant human bone morphogenetic protein 2 (rh-BMP-2) is frequently used in an off-label fashion. Its application for posterior interbody fusion appears intuitive because its use obviates the need for iliac crest bone graft and shows higher fusion rates than with the use of local autologous bone graft. To date, there is no report of adverse outcomes with such use of rh-BMP-2. PURPOSE: To draw attention to this unusual complication of posterior interbody lumbar fusion and to review the relevant literature. STUDY DESIGN: Clinical report of five cases of vertebral osteolysis that developed postoperatively from lumbar transforaminal interbody fusion of the L5/S1 motion segment using cages and rh-BMP-2. METHODS: Sixty-eight patients underwent transforaminal lumbar interbody fusion for spondylolisthesis or degenerative disc disease with discogenic back pain. Five of these 68 patients developed vertebral osteolysis within 4 months from their surgery. Their clinical presentation and radiographic findings are presented in this case series. RESULTS: Each one of these five patients had uneventful surgery and postoperative recovery. Their back and leg pain improved in the immediate postoperative period. However, each patient reported worsening back pain with variable radicular pain as early as 4 weeks and as late as 3 months after the index procedure. Diagnostic workup revealed evidence of vertebral osteolysis typically involving the L5 vertebral body. In all five patients, osteolytic defects filled in spontaneously, and symptoms typically resolved within an additional 3 months of nonoperative care. CONCLUSIONS: Vertebral osteolysis can occur with the use of rh-BMP-2 in posterior lumbar interbody fusions. Violation of the end plate during decortication may be a contributing factor. Symptoms often resolve spontaneously.