Surgical Treatment of Vertebral Osteomyelitis With Recombinant Human Bone Morphogenetic Protein-2

OʼShaughnessy, Brian A.; Kuklo, Timothy R.; Ondra, Stephen L.

doi:10.1097/brs.0b013e3181657ee3

Cited by 30 publications

(13 citation statements)

References 26 publications

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“…The use of growth factors for hard tissue reconstruction is gaining increased popularity and acceptance as clinicians, scientists, and patients search for less invasive therapies for craniofacial and orthopedic indications 17,18,36-40. Currently, most bone regenerative strategies using growth factors have focused on BMP-2, a potent osteoinductive molecule 41,42.…”

Section: Discussionmentioning

confidence: 99%

The Effect of NELL1 and Bone Morphogenetic Protein-2 on Calvarial Bone Regeneration

Aghaloo

Cowan

Zhang

et al. 2010

Journal of Oral and Maxillofacial Surgery

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Purpose Most craniofacial birth defects contain skeletal components that require bone grafting. Although many growth factors have shown potential for use in bone regeneration, bone morphogenetic proteins (BMPs) are the most osteoinductive. However, supraphysiologic doses, high cost, and potential adverse effects stimulate clinicians and researchers to identify complementary molecules that allow a reduction in dose of BMP-2. Because NELL1 plays a key role as a regulator of craniofacial skeletal morphogenesis, especially in committed chondrogenic and osteogenic differentiation, and a previous synergistic mechanism has been identified, NELL1 is an ideal molecule for combination with BMP-2 in calvarial defect regeneration. We investigated the effect of NELL1 and BMP-2 on bone regeneration in vivo. Materials and Methods BMP-2 doses of 589 and 1,178 ng were grafted into 5-mm critical-sized rat calvarial defects, as compared with 589 ng of NELL1 plus 589 ng of BMP-2 and 1,178 ng of NELL1 plus 1,178 ng of BMP-2, and bone regeneration was analyzed. Results Live micro–computed tomography data showed increased bone formation throughout 4 to 8 weeks in all groups but a significant improvement when the lower doses of each molecule were combined. High-resolution micro–computed tomography and histology showed more mature and complete defect healing when the combination of NELL1 plus BMP-2 was compared with BMP-2 alone at lower doses. Conclusion The observed potential synergy has significant value in the future treatment of patients with craniofacial defects requiring extensive bone grafting that would normally entail extraoral autogenous bone grafts or doses of BMP-2 in milligrams.

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Section: Discussionmentioning

confidence: 99%

The Effect of NELL1 and Bone Morphogenetic Protein-2 on Calvarial Bone Regeneration

Aghaloo

Cowan

Zhang

et al. 2010

Journal of Oral and Maxillofacial Surgery

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“…Remarkably, following contamination with only 500 colony‐forming units (CFU) S. aureus , BMP‐2 failed to induce spinal fusion in all 12 rabbits, while fusion occurred in all 13 non‐infected control rabbits. Although clinical investigations reported successful fusion rates for BMP‐2 in vertebral osteomyelitis, this discrepancy in outcome can be related to the additional debridement and antibiotic treatments performed in these patients …”

Section: What Is the Efficacy Of Osteoinductive Proteins In Infected mentioning

confidence: 99%

“…Although clinical investigations reported successful fusion rates for BMP-2 in vertebral osteomyelitis, this discrepancy in outcome can be related to the additional debridement and antibiotic treatments performed in these patients. 89,90 More numerous in vivo studies have investigated the impact of S. aureus infection on BMP-induced osteogenesis in the long bones, as overviewed in Supplementary Table S2. Critical size defects, by definition, will not heal without intervention and therefore represent the clinical scenario of a non-union where osteoinductive factors may be introduced.…”

Section: What Is the Efficacy Of Osteoinductive Proteins In Infected mentioning

confidence: 99%

Impact of Bacterial Infections on Osteogenesis: Evidence From In Vivo Studies

Croes

Wal

Charles

2019

Journal Orthopaedic Research

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The clinical impact of bacterial infections on bone regeneration has been incompletely quantified and documented. As a result, controversy exists about the optimal treatment strategy to maximize healing of a contaminated defect. Animal models are extremely useful in this respect, as they can elucidate how a bacterial burden influences quantitative healing of various types of defects relative to non‐infected controls. Moreover, they may demonstrate how antibacterial treatment and/or bone grafting techniques facilitate the osteogenic response in the harsh environment of a bacterial infection. Finally, it a well‐known contradiction that osteomyelitis is characterized by uncontrolled bone remodeling and bone loss, but at the same time, it can be associated with excessive new bone apposition. Animal studies can provide a better understanding of how osteolytic and osteogenic responses are related to each other during infection. This review discusses the in vivo impact of bacterial infection on osteogenesis by addressing the following questions (i) How does osteomyelitis affect the radiographic bone appearance? (ii) What is the influence of bacterial infection on histological bone healing? (iii) How do bacterial infections affect quantitative bone healing? (iv) What is the effect of antibacterial treatment on the healing outcome during infection? (v) What is the efficacy of osteoinductive proteins in infected bones? (vi) What is the balance between the osteoclastic and osteoblastic response during bacterial infections? (vii) What is the mechanism of the observed pro‐osteogenic response as observed in osteomyelitis? © 2019 The Authors. Journal of Orthopaedic Research© published by Wiley Periodicals, Inc. on behalf of Orthopaedic Research Society. J Orthop Res 37:2067–2076, 2019

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“…1,30 These studies provide evidence in support of the angiogenic abilities of BMP-2 and suggest that BMP, in combination with the ability of BMP to activate endothelial cells and stimulate vascular endothelial growth factor, may be the major mechanism coupling angiogenesis with osteogenesis. 1,30 Theoretically, increased osteoinduction combined with increased blood supply may lead to increased local antibiotic concentrations and more rapid eradication of infection. 1,30 In this way, we attempted to create an environment that strongly favors fusion, vascularity, antibiotic delivery, and eradication of infection, which occurred in our patient.…”

Section: Safety Concernsmentioning

confidence: 99%

“…1,30 Theoretically, increased osteoinduction combined with increased blood supply may lead to increased local antibiotic concentrations and more rapid eradication of infection. 1,30 In this way, we attempted to create an environment that strongly favors fusion, vascularity, antibiotic delivery, and eradication of infection, which occurred in our patient.…”

Section: Safety Concernsmentioning

confidence: 99%

Routine use of recombinant human bone morphogenetic protein–2 in posterior fusions of the pediatric spine and incidence of cancer

Sayama

Willsey

Chintagumpala

et al. 2015

PED

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OBJECT The aim of this study was to determine the safety of recombinant human bone morphogenetic protein–2 (rhBMP-2) use in posterior instrumented fusions in the pediatric population, focusing on cancer risk. In a previous study, the authors reported the short-term (mean follow-up of 11 months) safety and efficacy of rhBMP-2 in the pediatric age group. The present study reports their results with a minimum of 24 months' follow-up. METHODS The authors retrospectively reviewed 57 consecutive cases involving pediatric patients who underwent posterior occiptocervical, cervical, thoracic, lumbar, or lumbosacral spine fusion from October 1, 2007, to June 30, 2011, at Texas Children's Hospital. Seven cases were excluded from further analysis because of loss to follow-up. Three patients died during the follow-up period and were placed in a separate cohort. RESULTS The patients' average age at the time of surgery was 11 years, 4 months (range 9 months to 20 years). The mean duration of follow-up was 48.4 months (range 24–70 months). Cancer status was determined at the most recent encounter with the patient and/or caretaker(s) in person, or in telephone follow-up. Twenty-four or more months after administration of rhBMP-2, there were no cases of new malignancy, degeneration, or metastasis of existing tumors. The cause of death of the patients who died during the study period was not related to BMP or to the development, degeneration, or metastasis of cancer. CONCLUSIONS Despite the large number of adult studies reporting increased cancer risk associated with BMP use, the authors' outcomes with rhBMP-2 in the pediatric population suggest that it is a safe adjunct to posterior spine fusions of the occipitocervical, cervical, thoracic, lumbar, and lumbosacral spine. There were no new cases of cancer, or degeneration or metastasis of existing malignancies in this series.

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Surgical Treatment of Vertebral Osteomyelitis With Recombinant Human Bone Morphogenetic Protein-2

Abstract: rhBMP-2 is a valuable graft option for the surgical treatment of vertebral osteomyelitis. When dosed in the manner reported, very high rates of fusion are achievable as is eradication of infection.

Cited by 30 publications

References 26 publications

The Effect of NELL1 and Bone Morphogenetic Protein-2 on Calvarial Bone Regeneration

The Effect of NELL1 and Bone Morphogenetic Protein-2 on Calvarial Bone Regeneration

Impact of Bacterial Infections on Osteogenesis: Evidence From In Vivo Studies

Routine use of recombinant human bone morphogenetic protein–2 in posterior fusions of the pediatric spine and incidence of cancer

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