Off-Label Use of Bone Morphogenetic Protein 2 in the Reconstructions of Mandibular Continuity Defects

Oliveira, Marina Reis; Gorla, Luis Fernando de Oliveira; Gabrielli, Marisa Aparecida Cabrini; Pereira-Filho, Valfrido Antônio

doi:10.1097/scs.0000000000003291

Cited by 6 publications

(6 citation statements)

References 20 publications

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“…Lower level evidence exists for the use of rhBMP-2 in mandibular trauma, nonunion, osteonecrosis, osteomyelitis, and tumor resection (Table 2). 39–48 Orofacial edema is again the most common adverse event. Other complications such as nonunion, absence of bone regeneration, or hardware failure are difficult to attribute to rhBMP-2 rather than the surgical reconstruction itself.…”

Section: Discussionmentioning

confidence: 99%

Safety and Efficacy of Recombinant Human Bone Morphogenetic Protein-2 (rhBMP-2) in Craniofacial Surgery

Ramly

Alfonso

Kantar

et al. 2019

Plastic and Reconstructive Surgery - Global Open

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Introduction:Recombinant human bone morphogenetic protein-2 (rhBMP-2) is one of the most commonly used osteogenic agents in the craniofacial skeleton. This study reviews the safety and efficacy of rhBMP-2 as applied to craniofacial reconstruction and assesses the level of scientific evidence currently available.Methods:An extensive literature search was conducted. Randomized controlled trials (RCTs), case series and reports in the English language as well as Food and Drug Administration reports were reviewed. Studies were graded using the Oxford Center for Evidence-Based Medicine Levels of Evidence Scale. Data heterogeneity precluded quantitative analysis.Results:Seventeen RCTs (Levels of evidence: Ib-IIb) were identified evaluating the use of rhBMP-2 in maxillary sinus, alveolar ridge, alveolar cleft, or cranial defect reconstruction (sample size: 7–160; age: 8–75 years). Study designs varied in rigor, with follow-up ranging 3–36 months, and outcome assessment relying on clinical exam, radiology, and/or histology. There was wide variation in rhBMP-2 concentrations, carriers, and controls. Most studies evaluating rhBMP-2 for cranial defect closure, mandibular reconstruction, or distraction osteogenesis consisted of retrospective cohorts and case reports. The evidence fails to support RhBMP-2 use in maxillary sinus wall augmentation, calvarial reconstruction, mandibular reconstruction, or distraction osteogenesis. RhBMP-2 may be effective in alveolar reconstruction in adults, but is associated with increased postoperative edema.Conclusions:A risk–benefit ratio favoring rhBMP-2 over alternative substitutes remains to be demonstrated for most applications in plastic and reconstructive surgery. Long-term data on craniofacial growth is lacking, and using rhBMP-2 in patients younger than 18 years remains off-label.

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Section: Discussionmentioning

confidence: 99%

Safety and Efficacy of Recombinant Human Bone Morphogenetic Protein-2 (rhBMP-2) in Craniofacial Surgery

Ramly

Alfonso

Kantar

et al. 2019

Plastic and Reconstructive Surgery - Global Open

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“…Histology and scintigraphy were additionally used to assess bone viability. Histology was reported for only 15 patients in total 15,18,19,33,35,56,57 and scintigraphy for 19 patients in total. 13,15,[30][31][32]34,51,52,55 In contrast to other groups, all reports in the prefabrication group used scintigraphy to assess the vitality of the construct prior to flap harvest but not as an outcome measure of the reconstructed mandible.…”

Section: Discussionmentioning

confidence: 99%

“…Thirteen out of the 44 articles reported on series of patients with heterogenous defect characteristics, some of them not fulfilling the eligibility criteria. 19,22,32,34,39,[47][48][49][50][51]56,59,60 For these articles, individual patient data were examined and data from eligible patients were included in this review. Table 2 shows baseline characteristics of each treatment group.…”

Section: Included Study Characteristicsmentioning

confidence: 99%

“…In many of these reports, the outcomes were not provided as IPD but as summary information, so it was not possible to draw any conclusions on our population of interest (segmental mandible reconstruction). 13,15,18,19,22,[30][31][32][33][34][35]39,[47][48][49][50][51][52][55][56][57]59 Objective or quantifiable outcome criteria were hardly ever used. 13,15,18,19,[30][31][32][33][34][35]51,52,[55][56][57] The low level of evidence, the variability in the patient population and in the treatments (even within the same treatment group), and the lack of objective outcome measures did not allow to perform a quantitative synthesis of results or a comparison among patients or treatment groups.…”

Section: Strengths and Limitationsmentioning

confidence: 99%

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Segmental Mandibular Reconstruction Using Tissue Engineering Strategies: A Systematic Review of Individual Patient Data

Kumar

Rometsch²,

Thor

et al. 2020

Craniomaxillofacial Trauma & Reconstruction

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Objective: The aim of the systematic review was to analyze the current clinical evidence concerning the use of tissue engineering as a treatment strategy for reconstruction of segmental defects of the mandible and their clinical outcomes using individual patient data. Methods: A systematic review of the literature was conducted using PubMed and Cochrane Library on May 21, 2019. The eligibility criteria included patients in whom segmental mandibular reconstruction was carried out using tissue engineering as the primary treatment strategy. After screening and checking for eligibility, individual patient data were extracted to the extent it was available. Data extraction included the type of tissue engineering strategy, demographics, and indication for treatment, and outcomes included clinical and radiographic outcome measures, vitality of engineered bone, dental rehabilitation, and patient-reported outcome measures and complications. Results: Out of a total of 408 articles identified, 44 articles reporting on 285 patients were included, of which 179 patients fulfilled the inclusion criteria. The different tissue engineering treatment strategies could be broadly classified into 5 groups: “prefabrication,” “cell culture,” “bone morphogenetic protein (BMP) without autografts,” “BMP with autografts,” and “scaffolds containing autografts.” Most included studies were case reports or case series. A wide variety of components were used as scaffolds, cells, and biological substances. There was not a single outcome measure that was both objective and consistently reported, although most studies reported successful outcome. Discussion: A wide variety of tissue engineering strategies were used for segmental mandibular reconstruction that could be classified into 5 groups. Due to the low number of treated patients, lack of standardized and consistent reporting outcomes, lack of comparative studies, and low evidence of reported literature, there is insufficient evidence to recommend any particular tissue engineering strategy.

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“…These materials are mainly osteoconductive (Asahina, Watanabe, Sakurai, Mori, & Enomoto, 1997) and rely on the presence of preexisting periosteum and bone, which are not always located in mandibular defects (Moore, Graves, & Bain, 2001). In recent years, the use of bone morphogenetic proteins (BMPs) has been suggested as a promising biological treatment to induce bone regeneration (Carter, Brar, Tolas, & Beirne, 2008; Oliveira, Gorla, Gabrielli, & Pereira‐Filho, 2017). Nevertheless, use of BMPs has been associated with many adverse effects such as inflammation (Lee et al, 2012), inhibition of bone formation (Zara et al, 2011), bone cysts, and ectopic bone formation (Zara et al, 2011); and in some cases, related to spine surgery, it has led to neurological impairment (Wong, Kumar, Jatana, Ghiselli, & Wong, 2008).…”

Section: Introductionmentioning

confidence: 99%

Teriparatide (recombinant parathyroid hormone 1–34) enhances bone allograft integration in a clinically relevant pig model of segmental mandibulectomy

Pelled

Lieber

Avalos

et al. 2020

J Tissue Eng Regen Med

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Massive craniofacial bone loss poses a clinical challenge to maxillofacial surgeons.Structural bone allografts are readily available at tissue banks but are rarely used due to a high failure rate. Previous studies showed that intermittent administration of recombinant parathyroid hormone (rPTH) enhanced integration of allografts in a murine model of calvarial bone defect. To evaluate its translational potential, the hypothesis that rPTH would enhance healing of a mandibular allograft in a clinically relevant large animal model of mandibulectomy was tested. Porcine bone allografts were implanted into a 5-cm-long continuous mandible bone defect in six adult Yucatan minipigs, which were randomized to daily intramuscular injections of rPTH (1.75 μg/kg) and placebo (n = 3). Blood tests were performed on Day 56 preoperation, Day 0 and on Day 56 postoperation. Eight weeks after the surgery, bone healing was analyzed using high-resolution X-ray imaging (Faxitron and micro computed tomography [CT]) and three-point bending biomechanical testing. The results showed a significant 2.6-fold rPTH-induced increase in bone formation (p = 0.02). Biomechanically, the yield failure properties of the healed mandibles were significantly higher in the rPTH group (yield load: p < 0.05; energy to yield: p < 0.01), and the post-yield displacement and energy were higher in the placebo group (p < 0.05), suggesting increased mineralized integration of the allograft in the rPTH group. In contrast to similar rPTH therapy studies in dogs, no signs of hypercalcemia, hyperphosphatemia, or inflammation were detected. Taken together, we provide initial evidence that rPTH treatment enhances mandibular allograft healing in a clinically relevant large animal model.

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Off-Label Use of Bone Morphogenetic Protein 2 in the Reconstructions of Mandibular Continuity Defects

Cited by 6 publications

References 20 publications

Safety and Efficacy of Recombinant Human Bone Morphogenetic Protein-2 (rhBMP-2) in Craniofacial Surgery

Safety and Efficacy of Recombinant Human Bone Morphogenetic Protein-2 (rhBMP-2) in Craniofacial Surgery

Segmental Mandibular Reconstruction Using Tissue Engineering Strategies: A Systematic Review of Individual Patient Data

Teriparatide (recombinant parathyroid hormone 1–34) enhances bone allograft integration in a clinically relevant pig model of segmental mandibulectomy

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