Administration of Human Recombinant Bone Morphogenetic Protein-2 for Spine Fusion May Be Associated With Transient Postoperative Renal Insufficiency
ABSTRACT Retrospective chart review.
We reviewed the peri- and postoperative outcomes of our patients who had undergone lumbar and lumbosacral fusion both with and without recombinant human bone morphogenetic protein (rhBMP) over a period of 8 years to assess the frequency of complications and new diagnoses associated with the use of rhBMP2.
Administration of rhBMP2 for augmentation of lumbar and lumbosacral spinal fusion has not previously been associated with systemic complications.
A review of all patients undergoing lumbar and lumbosacral fusion over an 8-year period was performed to determine the frequency of postoperative complications and new diagnoses. Comparisons in complication frequency and new postoperative diagnoses between patients receiving rhBMP2 versus only allo- or autograft were made. Statistical methodology was applied to determine significance. RESULTS.: None of the 105 patients not receiving rhBMP2 and 3 of 24 patients receiving rhBMP2 had blood urea nitrogens and creatinines that more than doubled and reached values >30 and 1.5 mg/dL, respectively, after surgery (P = 0.006). Renal parameters returned to baseline within 45 days of surgery. Two of the 3 patients with postoperative renal insufficiency had been administered 16 mL (24 mg) of rhBMP2, whereas all other patients receiving rhBMP2 had received 8 mL (12 mg). Both of these patients also had supraventricular tachycardia, fever, and mental status changes after surgery. We recorded no significant increase in the incidence of new endocrinologic, autoimmune, neurologic, or neoplastic disorders associated with the use of rhBMP2 in our small patient population.
A small subset of patients may develop transient renal insufficiency after rhBMP2 to augment spinal fusion. Higher doses of rhBMP2 may possibly increase the risk of developing renal insufficiency in particular patients; however, additional study is needed before all the risk factors are understood.
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ABSTRACT: Introduction: Bone morphogenetic proteins are multi-functional growth factors, which play an important role in embryonic development and cellular functions. Among several molecules in this family, BMP-2 and BMP-7 are currently being used in the clinical setting. Main clinical targets include the treatment of non-union, open fractures and spinal fusion. Their use has not been without complications, one of which might be a carcinogenic effect. Areas covered: The authors offer a comprehensive review of the existing literature on the clinical studies analysing the role of bone morphogenetic proteins (BMPs) on carcinogenesis. The authors analyse the available literature and describe potential signalling pathways that can be affected as per available experimental in vitro and in vivo models. Expert opinion: The available experimental data and clinical evidence are rather inadequate to allow any safe scientific conclusions. Clinical studies provide incomplete evidence to support the hypothesis that BMPs are carcinogenic. The available literature has several limitations including incomplete documentation, unreported data and inhered bias as a large number of trials have been funded by the industry. The need of well-structured studies is essential to address these safety concerns.Expert Opinion on Drug Safety 09/2014; 13(11). DOI:10.1517/14740338.2014.968124 · 2.74 Impact Factor
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ABSTRACT: 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.05/2012; 3(2):35-41. DOI:10.1055/s-0031-1298616
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ABSTRACT: Medtronic's INFUSE Bone Graft provides surgeons with a potent tool for stimulating bone formation. Current delivery vehicles that rely on Absorbable Collagen Sponges (ACS) require excessive quantities of the active ingredient in INFUSE, recombinant human Bone Morphogenic Protein-2 (rhBMP2), to achieve physiologically relevant concentrations of the growth factor, driving up the cost of the product and increasing the likelihood of undesirable side effects in neighboring tissues. We demonstrate that a simple light-mediated, thiol-ene chemistry can be used to create an effective polymer delivery vehicle for rhBMP2, eliminating the use of xenographic materials and reducing the dose of rhBMP2 required to achieve therapeutic effects. Comprised entirely of synthetic components, this system entraps rhBMP2 within a biocompatible hydrogel scaffold that is degraded by naturally occurring remodeling enzymes, clearing the way for new tissue formation. When tested side-by-side with ACS in a critical-sized bone defect model in rats, this polymeric delivery system significantly increased bone formation over ACS controls. © 2012 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res.Journal of Orthopaedic Research 03/2013; 31(3). DOI:10.1002/jor.22243 · 2.97 Impact Factor