Complications and cancer rates in spine fusion with recombinant human bone morphogenetic protein-2 (rhBMP-2)

Vavken, Julia; Mameghani, Alexander; Vavken, Patrick; Schaeren, Stefan

doi:10.1007/s00586-015-3870-9

Cited by 34 publications

(11 citation statements)

References 64 publications

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“…Although clinical findings appertaining to the use of BMP-2 in spinal fusion are fairly impressive, the success of the procedure is often overshadowed by the manifestation of severe undesired side effects, which can seriously impair the health and the musculoskeletal functions of the treated patient (Faundez et al, 2016;James et al, 2016). These include ectopic bone formation, paralysis and neurological disturbances (Hofstetter et al, 2016;Vavken et al, 2015) [but not malignant pathologies (Cahill et al, 2015;Malham et al, 2015)]. …”

Section: Introductionmentioning

confidence: 99%

Optimisation of BMP-2 dosage for the osseointegration of porous titanium implants in an ovine model

Hunziker

Jovanovic²,

Hörner³

et al. 2016

eCM

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In clinical orthopaedics, total joint replacements and spinal fusions are routine undertakings. Many of the implicated patients suffer from osteoporosis, severe arthrosis or osteopaenia. In individuals thus afflicted, the bony bed lacks the mechanical stability that is a requisite for a firm anchorage of the implant and its functional competence. To promote the bony bondage of an implant it is necessary to induce neo-ossification by the introduction of an osteogenic agent, such as bone morphogenetic protein 2 (BMP-2). Since this growth factor is generally applied in a free form and at high dosages to maximise its osteogenicity, untoward side effects frequently ensue.We hypothesise that the administration of BMP-2 using a suitable delivery vehicle, and its gradual, low dose release therefrom in a cell-mediated manner, would avert the triggering of undesired side effects and enhance its efficacy.To test this postulate, implants of porous titanium were coated with a layer of calcium phosphate into which BMP-2 was biomimetically incorporated at dosages ranging from 0.8 to 500 µg/g of coating material (delivery system) prior to their surgical placement in the tibiae of adult sheep. The volume and the surface area of newly-formed bone were evaluated histomorphometrically after 3 and 6 weeks. The highest values were achieved using BMP-2 dosages of 20 to 100 µg/g of coating: The deposition of bone was confined to the immediate vicinity of the implant and was observed deep within the interstices of its meshwork, to the walls of which it bonded well. The findings of the study attest to the validity of our hypothesis.

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Section: Introductionmentioning

confidence: 99%

Optimisation of BMP-2 dosage for the osseointegration of porous titanium implants in an ovine model

Hunziker

Jovanovic²,

Hörner³

et al. 2016

eCM

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“…The possibility that the fusion substrate could stimulate the growth of cancer cells is removed. 70–73 Finally, fusion materials are expensive. Cellular allograft and demineralized bone matrix are fusion substrate options in cancer patients; however; they carry a substantial financial cost.…”

Section: Discussionmentioning

confidence: 99%

Instrumented Spinal Stabilization without Fusion for Spinal Metastatic Disease

2018

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Objectives Spinal stabilization surgery is an integral part of the treatment of spinal metastatic disease. Bony fusion is the hallmark of spinal stabilization in non-oncology patients. Spinal oncology patients are unlikely to achieve bony fusion due to their overall prognosis and concurrent therapies. Stabilization surgery without fusion may be a reasonable approach for these patients. Literature evaluating the effectiveness of this approach is limited. The object of this study was to investigate the rate of instrumentation failure in patients undergoing posterior spinal instrumented stabilization without fusion for spinal metastatic disease. Methods Data from consecutive cases of spinal surgery at our institution during an 81-month period were reviewed. Demographics, clinical notes, and computed tomography (CT) findings were recorded and used to evaluate instrumentation failures. Patients who underwent separation surgery that included laminectomy and posterior spinal instrumentation without fusion for spinal metastatic disease and had follow-up CT scans >3 months postoperatively were selected for the study. Results Twenty-seven patients were included in the study. Mean age was 64.85±6.53 years. Nine patients were women. A mean of 1.61±0.96 laminectomy levels was performed. A mean of 8.26±1.48 screws was inserted. The mean postoperative discharge date was 5.07±1.47 days. Mean follow-up duration was 12.17±11.73 months. None of the patients had a change in instrumentation position, pedicle screw pullout, change in spinal alignment, or progressive deformity. No patient required reoperation or instrumentation revision or replacement. Conclusions Our experience suggests that instrumented spinal stabilization without fusion is an acceptable approach for patients with spinal metastatic disease.

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“…While a recent meta-analysis by Cahill et al 11 revealed that there was no conclusive evidence that BMP-2 was associated with the formation of cancer locally or at a distant site, there remains concern regarding its potential carcinogenicity. 58,62,63,66 Although the use of local bone grafts are relatively contraindicated following spinal column tumor resection, patients in 3 studies 19,41,54 received morselized local bone grafts. Of note, Coumans et al 19 reported the use of a vertebral autograft that contained tumor, after the diagnosis of benign intraosseous schwannoma was confirmed by intraoperative pathological diagnosis.…”

Section: Discussionmentioning

confidence: 99%

“…8,9,27,31,40 Additionally, although controversial, the application of bone morphogenetic protein-2 (BMP-2) to patients with tumors is generally contraindicated due to several prior studies that suggested an increased incidence of tumors in patients who received BMP-2. 58,62,63,66 Because of these issues, it is unclear what bone graft options should be selected in patients with spinal column tumors. The literature is also significantly limited, as a majority of prior reports were either retrospective with small numbers of patients, 1,36 or case reports, 5 focusing on survival outcomes or technical aspects of surgery rather than fusion outcomes.…”

mentioning

confidence: 99%

Bone graft options for spinal fusion following resection of spinal column tumors: systematic review and meta-analysis

Elder

Ishida

Goodwin

et al. 2017

FOC

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OBJECTIVE With the advent of new adjunctive therapy, the overall survival of patients harboring spinal column tumors has improved. However, there is limited knowledge regarding the optimal bone graft options following resection of spinal column tumors, due to their relative rarity and because fusion outcomes in this cohort are affected by various factors, such as radiation therapy (RT) and chemotherapy. Furthermore, bone graft options are often limited following tumor resection because the use of local bone grafts and bone morphogenetic proteins (BMPs) are usually avoided in light of microscopic infiltration of tumors into local bone and potential carcinogenicity of BMP. The objective of this study was to review and meta-analyze the relevant clinical literature to provide further clinical insight regarding bone graft options. METHODS A web-based MEDLINE search was conducted in accordance with preferred reporting items for systematic review and meta-analysis (PRISMA) guidelines, which yielded 27 articles with 383 patients. Information on baseline characteristics, tumor histology, adjunctive treatments, reconstruction methods, bone graft options, fusion rates, and time to fusion were collected. Pooled fusion rates (PFRs) and I2 values were calculated in meta-analysis. Meta-regression analyses were also performed if each variable appeared to affect fusion outcomes. Furthermore, data on 272 individual patients were available, which were additionally reviewed and statistically analyzed. RESULTS Overall, fusion rates varied widely from 36.0% to 100.0% due to both inter- and intrastudy heterogeneity, with a PFR of 85.7% (I2 = 36.4). The studies in which cages were filled with morselized iliac crest autogenic bone graft (ICABG) and/or other bone graft options were used for anterior fusion showed a significantly higher PFR of 92.8, compared with the other studies (83.3%, p = 0.04). In per-patient analysis, anterior plus posterior fusion resulted in a higher fusion rate than anterior fusion only (98.8% vs 86.4%, p < 0.001). Although unmodifiable, RT (90.3% vs 98.6%, p = 0.03) and lumbosacral tumors (74.6% vs 97.9%, p < 0.001) were associated with lower fusion rates in univariate analysis. The mean time to fusion was 5.4 ± 1.4 months (range 3–9 months), whereas 16 of 272 patients died before the confirmation of solid fusion with a mean survival of 3.1 ± 2.1 months (range 0.5–6 months). The average time to fusion of patients who received RT and chemotherapy were significantly longer than those who did not receive these adjunctive treatments (RT: 6.1 months vs 4.3 months, p < 0.001; chemotherapy: 6.0 months vs 4.3 months, p = 0.02). CONCLUSIONS Due to inter- and intrastudy heterogeneity in patient, disease, fusion criteria, and treatment characteristics, the optimal surgical techniques and factors predictive of fusion remain unclear. Clearly, future prospective, randomized studies will be necessary to better understand the issues surrounding bone graft selection following resection of spinal column tumors.

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Complications and cancer rates in spine fusion with recombinant human bone morphogenetic protein-2 (rhBMP-2)

Abstract: rhBMP-2 is associated with a higher rate of general complications as well as retrograde ejaculation, HO, and cervical tissue swelling in spine fusion. There is a slightly increased risk of new onset of tumors, however, without statistical significance.

Cited by 34 publications

References 64 publications

Optimisation of BMP-2 dosage for the osseointegration of porous titanium implants in an ovine model

Optimisation of BMP-2 dosage for the osseointegration of porous titanium implants in an ovine model

Instrumented Spinal Stabilization without Fusion for Spinal Metastatic Disease

Bone graft options for spinal fusion following resection of spinal column tumors: systematic review and meta-analysis

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