Administration of Human Recombinant Bone Morphogenetic Protein-2 for Spine Fusion May Be Associated With Transient Postoperative Renal Insufficiency

Latzman, Jonathan M.; Kong, Li; Liu, Chuanju; Samadani, Uzma

doi:10.1097/brs.0b013e3181c71447

Cited by 20 publications

(12 citation statements)

References 18 publications

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“…One cohort study was also found comparing rhBMP-2 with ICBG for various surgical approaches 10. Another study which conducted a review of the Medicare database to assess the risk for pancreatic cancer only was also included 11…”

Section: Resultsmentioning

confidence: 99%

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The use of rhBMP in spine surgery: is there a cancer risk?

DeVine

Dettori

France

et al. 2012

Evidence-Based Spine-Care Journal

105

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Study design: Systematic review.Study rationale: Some have noted several safety issues associated with the use of bone morphogenetic proteins (BMPs), including cancer risk, stating both BMP and their receptors had been isolated from human tumors. In addition, data presented to the US Food and Drug Administration (FDA) on the product AMPLIFY™ (rhBMP-2, 40 mg) revealed a higher number of cancers in the investigational group compared with the control.Objective: To independently review the cancer risk of rhBMP-2 use in spine fusion as published in the peer-reviewed literature and in the publicly available FDA data summaries.Methods: A systematic review of the literature was undertaken for articles published through January 2012. Pubmed, Cochrane, National Guideline Clearinghouse Databases as well as bibliographies of key articles were searched. Two independent reviewers revised articles. Inclusion and exclusion criteria were set and each article was subjected to a predefined quality-rating scheme.Results: Five published peer-reviewed studies and two FDA safety summaries reported the occurrence of cancer in patients treated with spinal fusion using rhBMP-2 or rhBMP-7. Cancer data for on-label use of rhBMP-2 (InFUSE™) were reported in the FDA data summary but not in one published pivotal study. The risk of cancer was same in both the rhBMP-2 and control groups, 0.7% after 24 months. Off-label use of rhBMP for posterolateral fusion (PLF) was associated with a slightly higher risk of cancer compared with controls in three randomized controlled trials and one poorly conducted retrospective cohort study at various follow-ups. In PLF the risk of cancer was 3.8% using 40 mg of BMP-2 compared with 0.9% in the control group. Two RCTs evaluating rhBMP-7 reported a cancer risk of 12.5% and 5.6% in the rhBMP-7 group compared with 8.3% and 0% in the control groups, respectively. The differences in these studies were not statistically significant; however, the sample sizes for these studies were small.Conclusions: Cancer risk with BMP-2 may be dose dependent, illustrating the need to continue to study this technology and obtain longer follow-up on patients currently enrolled in the FDA trials. Additionally, refined guidelines regarding the routine use of BMPs should be developed, taking into account the FDA summary data that is not routinely scrutinized by the practicing surgeon.

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Section: Resultsmentioning

confidence: 99%

“…Off-label use of rhBMP for posterolateral fusion (PLF) was associated with a slightly higher risk of cancer compared with controls in three randomized controlled trials3,4,5,6,7,8 and one poorly conducted retrospective cohort study10 (Table 1). …”

Section: Resultsmentioning

confidence: 99%

The use of rhBMP in spine surgery: is there a cancer risk?

DeVine

Dettori

France

et al. 2012

Evidence-Based Spine-Care Journal

105

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“…Similarly, painful seroma or epidural haematoma was never mentioned as a side effect of ALIF, although some cases were reported in TLIF surgeries, posterolateral lumbar fusions and anterior cervical fusions [46,47]. Latzman et al [30] raised a potential concern about transient renal impairment associated with rhBMP-2 in a small retrospective cohort of 24 patients, controlled with 105 patients who underwent lumbar or lumbosacral fusion [48]. A case report was also published on similar effects.…”

Section: Resultsmentioning

confidence: 99%

Bone morphogenetic protein use in spine surgery—complications and outcomes: a systematic review

Faúndez

Tournier

Garcia

et al. 2016

International Orthopaedics (SICOT)

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This literature review confirms that the use of rhBMP-2 following FDA-approved recommendations (i.e. one-level ALIF surgery with an LT-cage) is safe. The rate of complications is low and the AEs had been identified by the FDA during the pre-marketing clinical trials. The clinical efficiency of rhBMP-2 is equal or superior to that of allogenic or autologous bone graft in respect to fusion rate, low back pain disability, patient satisfaction and rate of re-operations. For all other off-label use, the safety and effectiveness of rhBMP-2 have not been established, and further RCTs with high level of evidence are required.

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“…Cancer 19,20,27,[35][36][37][38][39][40] BMP-2 has significant inhibitory effects on the tumorigenic potential of cancer stem cells.…”

Section: Bmp-2: Usesmentioning

confidence: 99%

“…Humans Complications requiring additional surgery, instrumentation failure, neurological deficit, deep wound infection More complications, longer operative time and greater anteroposterior fusion than no BMP due to off-label use Spine surgery [31] (2013) Posterolateral lumbar spine arthrodesis [35] (2009) 426 Humans 10 cases who developed cancer of which 8 were treated with rhBMP-2 and 2 treated with iliac bone graft Slight correlation between the use of rhBMP-2 and risk of cancer Further research needs to be performed Spine fusion [36] (2010) 129 Humans Postoperative cancer found in 17% who received rhBMP-2 compared to 8% who did not…”

mentioning

confidence: 99%

Bone morphogenetic protein-2 and bone therapy: successes and pitfalls

Poon

Kha

Tran

et al. 2016

Journal of Pharmacy and Pharmacology

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Objectives Bone morphogenetic proteins (BMPs), more specifically BMP-2, are being increasingly used in orthopaedic surgery due to advanced research into osteoinductive factors that may enhance and improve bone therapy. There are many areas in therapy that BMP-2 is being applied to, including dental treatment, open tibial fractures, cancer and spinal surgery. Within these areas of treatment, there are many reports of successes and pitfalls. This review explores the use of BMP-2 and its successes, pitfalls and future prospects in bone therapy. Methods The PubMed database was consulted to compile this review. Key findings With successes in therapy, there were descriptions of a more rapid healing time with no signs of rejection or infection attributed to BMP-2 treatment. Pitfalls included BMP-2 'off-label' use, which lead to various adverse effects. Conclusions Our search highlighted that optimising treatment with BMP-2 is a direction that many researchers are exploring, with areas of current research interest including concentration and dose of BMP-2, carrier type and delivery.

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Administration of Human Recombinant Bone Morphogenetic Protein-2 for Spine Fusion May Be Associated With Transient Postoperative Renal Insufficiency

Cited by 20 publications

References 18 publications

The use of rhBMP in spine surgery: is there a cancer risk?

The use of rhBMP in spine surgery: is there a cancer risk?

Bone morphogenetic protein use in spine surgery—complications and outcomes: a systematic review

Bone morphogenetic protein-2 and bone therapy: successes and pitfalls

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