clearly demonstrated. Bone morphogenetic proteins have some characteristic features that distinguish them from other therapeutic proteins regarding immunogenicity. Whereas most therapeutic proteins are used to correct an acquired or genetic deficiency caused by the absence or poor expression of a native protein, 1 , 54 rhBMPs were developed to enhance spinal fusion and fracture healing. 70 That is, BMPs are administered locally to address local challenges in bone regeneration and repair, unlike most therapeutic proteins that are administered systemically. The route
Chang Ju Hwang, Alexander R. Vaccaro, James P. Lawrence, Joseph Hong, Huub Schellekens, Moulay Hicham Alaoui-Ismaili and Dean Falb
Setti S. Rengachary
The cellular and molecular events governing bone formation in the embryo, healing of a fractured bone, and induced bone fusion follow a similar pattern. Discovery, purification, and recombinant synthesis of bone morphogenetic proteins (BMPs) constiute a major milestone in the understanding of bone physiology. In this review the author discusses the mechanism of action, clinical applications, dosage, and optimum carriers for BMPs. The roles played by other growth factors are also discussed.
Tord D. Alden, Debra D. Pittman, Elisa J. Beres, Gerald R. Hankins, David F. Kallmes, Benjamin M. Wisotsky, Kelvin M. Kerns and Gregory A. Helm
addition of osteoconductive matrices and osteoinductive growth factors to the autograft are currently being investigated. Bone morphogenetic proteins (BMPs) have been shown to be extremely effective in enhancing bone deposition at fusion sites in a variety of animal models and are currently being tested in phase I clinical trials for the treatment of spondylolisthesis. The BMPs comprise a family of proteins within the transforming growth factor—β superfamily based on amino acid homology. 2, 3, 13, 14 When applied in vivo, many of the BMPs induce ectopic bone formation
Takano Bunakase, Kenta Ariga, Shimpei Miyamoto, Shin'ya Okuda, Tetsuya Tomita, Motoki Iwasaki, Kazuo Yonenobu and Hideki Yoshikawa
kind of chondrogenesis is reported to be regulated by various factors, 17 and similarly, various molecules may become key factors in the regulation of chondrogenesis in spondylosis. Bone morphogenetic protein is a key molecule that can induce the formation of bone and cartilage in vivo. 29, 30 We have previously purified mice BMP-4, 26 cloned its cDNA, 25 and reported that the BMP-4 gene is induced in the early phase of fracture repair, suggesting that newly synthesized BMP-4 is a stimulus for chondrogenesis in fracture callus formation in vivo. 15 In
Osamah J. Choudhry, Lana D. Christiano, Rahul Singh, Barbara M. Golden and James K. Liu
version of the manuscript on behalf of all authors: Liu. Study supervision: Liu. This article contains some figures that are displayed in color online but in black and white in the print edition. Presented at the 2010 Spine Section Meeting. References 1 Benglis D , Wang MY , Levi AD : A comprehensive review of the safety profile of bone morphogenetic protein in spine surgery . Neurosurgery 62 : 5 Suppl 2 ONS423 – ONS431 , 2008 2 Burkus JK , Dorchak JD , Sanders DL : Radiographic assessment of interbody fusion using recombinant human
David H. Walker and Neill M. Wright
Bone morphogenetic proteins (BMPs) have increasingly become a focus of research in the laboratory, with animal models, and in human clinical trials for the treatment of spinal disorders. Basic science research has elucidated the putative mechanism of action of BMPs, and the efficacy of BMPs in inducing bone formation has been evaluated in multiple animal models of anterior and posterior spinal fusion. Not only has BMP been shown to improve the quality and amount of bone formation when used as a supplement to autograft, it has also been shown to promote superior fusion in the absence of autograft, even in high-risk fusion models involving the use of nicotine or nonsteroidal antiinflam-matory agents. Both completed and ongoing clinical trials have demonstrated the efficacy of recombinant BMP, leading to the first BMP product being approved for clinical use earlier this year.
Animal models and clinical trials have also been used to evaluate the safety of BMPs. Although few complications have been reported, BMPs can induce heterotopic bone formation, especially when placed adjacent to exposed neural elements. Potentially more serious, antibody formation has been seen in up to 38% of patients in some clinical trials. No clinical sequelae have been reported despite the development of antibodies against BMP, a naturally occurring human protein implicated in processes other than osteoinduction.
The future directions of biological manipulation of the osteoinduction process include further understanding of the interactions of the BMP subtypes, the interactions of BMP with its receptors, and exploring other molecules capable of osteoinduction.
Gregory A. Helm, Tord D. Alden, Elisa J. Beres, Sarah B. Hudson, Subinoy Das, Jonathan A. Engh, Debra D. Pittman, Kelvin M. Kerns and David F. Kallmes
newly formed bone, minimize the time course for osteoinduction, and improve the final biomechanical properties of the genetically engineered bone. 22 Acknowledgment The Ad-β-gal was a gift from Dr. C. Kao of the University of Virginia Cancer Center. References 1. Alden TD , Beres EJ , Laurent JS , et al : The use of bone morphogenetic protein gene therapy for craniofacial bone repair. J Craniofac Surg 11 : 24 – 30 , 2000 Alden TD, Beres EJ, Laurent JS, et al: The use of bone morphogenetic protein gene
Maxwell Boakye, Praveen V. Mummaneni, Mark Garrett, Gerald Rodts and Regis Haid
rhBMP in conjunction with an anterior cervical plate promise to be an alternative way of achieving excellent arthrodesis in patients with cervical disc disease. Abbreviations used in this paper ACDF = anterior cervical discectomy and fusion ; BMP = bone morphogenetic protein ; CT = computerized tomography ; ICBG = iliac crest bone graft ; MR = magnetic resonance ; MVA = motor vehicle accident ; PEEK = polyetheretherketone ; rhBMP = recombinant human BMP
Alan T. Villavicencio, Sigita Burneikiene, E. Lee Nelson, Ketan R. Bulsara, Mark Favors and Jeffrey Thramann
, effective, and safe method of spinal lumbar fusion. Abbreviations used in this paper ACS = absorbable collagen sponge ; AICB = autologous iliac crest bone ; ALIF = anterior lumbar interbody fusion ; BMP = bone morphogenetic protein ; CT = computerized tomography ; EBL = estimated blood loss ; LOS = length of stay ; PLF = posterolateral fusion ; PS = pedicle screw ; PSF = PS fixation ; rhBMP-2 = recombinant human BMP-2 ; SD = standard
Daniel C. Lu and Peter P. Sun
C raniovertebral instability is a well-known phenomenon in patients with Down syndrome. 16 Symptomatic instability can occur at a young age. Achieving craniovertebral fusion, however, can be particularly challenging in these infants. 8 , 14 , 17 , 19 Bone morphogenetic protein was discovered in 1965 in the extracellular matrix of bone to have the capacity to induce new bone formation. 22 Given the success of rhBMP-2 in promoting spinal fusion, we present the use of rhBMP-2 in a challenging case of an infant with Down syndrome and craniovertebral