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

Faúndez, Antonio; Tournier, C.; Garcia, Matthieu; Aunoble, S.; Huec, Jean-Charles Le

doi:10.1007/s00264-016-3149-8

Cited by 66 publications

(52 citation statements)

References 65 publications

(205 reference statements)

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“…Particularly, the pro‐osteogenic effect of BMP‐2 has been widely studied . On the negative side, rapid degradation and enzymatic deactivation of BMP‐2 as well as its numerous side‐effects (i.e., neurological deficits or heterotopic ossifications) limit its potential application . A “milder” way of stimulating bone ingrowth and vascularization of HA scaffolds might be the usage of ECM proteins.…”

Section: Discussionmentioning

confidence: 99%

Effect of bone sialoprotein coated three‐dimensional printed calcium phosphate scaffolds on primary human osteoblasts

et al. 2018

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The combination of the two techniques of rapid prototyping 3D-plotting and bioactive surface functionalization is presented, with emphasis on the in vitro effect of Bone Sialoprotein (BSP) on primary human osteoblasts (hOBs). Our primary objective was to demonstrate the BSP influence on the expression of distinctive osteoblast markers in hOBs. Secondary objectives included examinations of the scaffolds' surface and the stability of BSP-coating as well as investigations of cell viability and proliferation. 3D-plotted calcium phosphate cement (CPC) scaffolds were coated with BSP via physisorption. hOBs were seeded on the coated scaffolds, followed by cell viability measurements, gene expression analysis and visualization. Physisorption is an effective method for BSP-coating. Coating with higher BSP concentrations leads to enhanced BSP release. Two BSP concentrations (50 and 200 μg/mL) were examined in this study. The lower BSP concentration (50 µg/mL) decreased ALP and SPARC expression, whereas the higher BSP concentration (200 μg/mL) did not change gene marker expression. Enhanced cell viability was observed on BSP-coated scaffolds on day 3. hOBs developed a polygonal shape and connected in an intercellular network under BSP influence. Quantitative cell morphology analyses demonstrated for BSP-coated CPCs an enhanced cell area and reduced circularity. The strength of the above-mentioned effects of BSP-coated scaffolds in vivo is unknown, and future work is focusing on bone ingrowth and vascularization in vivo. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 2565-2575, 2018.

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Section: Discussionmentioning

confidence: 99%

Effect of bone sialoprotein coated three‐dimensional printed calcium phosphate scaffolds on primary human osteoblasts

et al. 2018

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“…The most severe complications were described in spine surgery, where the use of rhBMP-2 was associated with an increasing rate of vertebral osteolysis, graft subsidence, graft migration, formation of neutralizing antibodies against BMPs, radiculitis, haematoma or seroma, ectopic bone formation, pulmonary and neurological complications [60][61][62]. Due to these problems and to the high proportion of surgery performed with BMPs deviating for the original approved indications [63], the FDA issued a warning regarding the off label use of rhBMP-2 (INFUSE®) in cervical spine [64]. Considering the potential adverse events of BMPs, this systematic review on the treatment of bone fractures, non union, and osteonecrosis, also focused on the literature evidence of complications related to these orthopaedic conditions.…”

Section: Complicationsmentioning

confidence: 99%

Clinical application of bone morphogenetic proteins for bone healing: a systematic review

Krishnakumar

Roffi

Reale

et al. 2017

International Orthopaedics (SICOT)

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Purpose This paper documents the existing evidence on bone morphogenetic proteins (BMPs) use for the treatment of bone fractures, non-union, and osteonecrosis, through a review of the clinical literature, underlying potential and limitations in terms of cost effectiveness and risk of complications. Methods A systematic review was performed on the PubMed database using the following string: (bone morphogenetic proteins OR BMPs) and (bone repair OR bone regeneration) including papers from 2000 to 2016. The search focused on clinical trials dealing with BMPs application to favor bone regeneration in bone fractures, non-union, and osteonecrosis, in English language, with level of evidence I, II, III, and IV. Relevant data (type of study, number of patients, BMPs delivery material, dose, site, follow-up, outcome, and adverse events) were extracted and analyzed. Results Forty-four articles met the inclusion criteria: 10 randomized controlled trials (RCTs), 7 comparative studies, 18 case series, and 9 case reports. rhBMP-2 was documented mainly for the treatment of fractures, and rhBMP-7 mainly for non-unions and osteonecrosis. Mixed results were found among RCTs and comparative papers: 11 reported positive results for BMPs augmentation, 3 obtained no significant effects, and 2 showed negative results. The only study comparing the two BMPs showed a better outcome with rhBMP-2 for non-union treatment. Conclusion Clinical evidence on BMPs use for the treatment of fractures, non-union, and osteonecrosis is still controversial, with the few available reports being mainly of low quality. While positive findings have been described in many studies, mixed results are still present in the literature in terms of efficacy and adverse events. The difficulties in drawing clear conclusions are also due to the studies heterogeneity, mainly in terms of different BMPs applied, with different concomitant treatments for each bone pathology. Therefore, further research with well-designed studies is needed in order to understand the real potential of this biological approach to favour bone healing.

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“…The optimum release pattern of rhBMP-2 has remained to be established, and excessive dosages of BMP may be dangerous, as they have other effects in processes including organogenesis, cell differentiation, cell proliferation and apoptosis. Furthermore, the production and purification of the recombinant protein is costly, making this therapy expensive (12–14). …”

Section: Introductionmentioning

confidence: 99%

Combination therapy with BMP‑2 and psoralen enhances fracture healing in ovariectomized mice

Huang

et al. 2018

Exp Ther Med

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The advantages of combining local delivery of bone morphogenetic protein (BMP)-2 with systemic or local anti-osteoporosis treatments have also been studied for enhancing osteoporotic fracture healing. The aim of the present study was to evaluate the effect of combination therapy with BMP-2 and psoralen on fracture repair in ovariectomized mice. At 6 weeks after bilateral ovariectomy, mice (n=30) underwent unilateral transverse osteotomy on the femur and were divided into 3 groups. In the model group (n=10), animals were implanted with an absorbable collagen sponge (ACS) alone and administered physiological saline intragastrically (i.g.). In the recombinant human (rh)BMP-2 group (n=10), animals were implanted with an ACS loaded with 2.5 µg rhBMP-2 and administered physiological saline i.g. In the psoralen + rhBMP-2 group (n=10) animals were implanted with an ACS loaded with 2.5 µg rhBMP-2 and administered psoralen i.g. The mice were euthanized after 21 days and their fractured femurs were assessed by micro computed tomography, histological analysis and biomechanical testing. Furthermore, the serum of the animals was analyzed. Psoralen + rhBMP-2 exerted more beneficial effects on callus consolidation and biomechanical strength. In addition, increased bone-specific alkaline phosphatase levels and decreased C-terminal telopeptide of type-1 collagen were observed in the Psoralen + rhBMP-2 group. However, no difference in estrogen levels was detected between the groups. In conclusion, the present study demonstrated that in ovariectomized mice, combination of locally delivered BMP-2 and systemically administered psoralen improved bone healing compared with BMP-2 alone.

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

Cited by 66 publications

References 65 publications

Effect of bone sialoprotein coated three‐dimensional printed calcium phosphate scaffolds on primary human osteoblasts

Effect of bone sialoprotein coated three‐dimensional printed calcium phosphate scaffolds on primary human osteoblasts

Clinical application of bone morphogenetic proteins for bone healing: a systematic review

Combination therapy with BMP‑2 and psoralen enhances fracture healing in ovariectomized mice

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