Prevalence, Complications, and Hospital Charges Associated With Use of Bone-Morphogenetic Proteins in Spinal Fusion Procedures

Abstract

leading cause of disability in the United States and is one of the most common reasons for seeking evaluation by a physician, second only to the common cold. 1-3 Nonsurgical interventions remain the firstline of therapy; however, many patients eventually progress to surgical treatments with 1 option including fusion. Spinal arthrodesis (fusion) as a treatment for back pain has rapidly evolved with the development of advanced spinal instrumentation and biologics to promote bony fusion. 4 Bone-morphogenetic proteins (BMPs) represent a family of differentiation factors that promote bone creation and remodeling. 5 Clinical use of recombinant BMP protein was approved by the US Food and Drug Administration (FDA) in 2002 for surgery of the anterior lumbar spine to promote bone fusion. 6 Two BMP products are commercially available for clinical use, BMP-2 (INFUSE, Medtronic, Memphis, Tennessee) and BMP-7 (OP-1 Putty, Stryker, Kalamazoo, Michigan). BMP-2 is approved for anterior lumbar interbody fusion in skeletally mature patients and BMP-7 received a humanitarian use device approval in 2003 for revision inter-transverse lumbar fusion in compromised patients. 6,7 Due to robust bone forming properties, BMP use may increase the likelihood of bony fusion thereby decreasing the undesired outcome of pseudarthrosis or nonunion. 8

Delivery of Phenamil Enhances BMP-2-Induced Osteogenic Differentiation of Adipose-Derived Stem Cells and Bone Formation in Calvarial Defects

“…28 While BMPs have successfully induced bone formation in vivo, high dose requirements and paradoxical activities of BMPs on progenitor cells may lead to unexpected side effects such as ectopic bone formation while also rendering high treatment costs to patients. [5][6][7][8] In this study, we employed a small molecule that can effectively complement the pro-osteogenic activity of BMP-2 to maximize biological efficiency, thereby reducing the total dose requirement (cost) and minimizing potential adverse effects associated with BMP-2. Small molecular therapeutics has several advantages over protein-based therapeutics due to their lower cost and ease of manufacturing and storage compared with growth factor proteins.…”

“…Unfortunately, along with high cost, application of such high doses has revealed numerous side effects, such as vertebral osteolysis with cyst formation and life-threatening inflammatory cervical swelling, which have been well documented. [5][6][7][8] Thus, there is a need to develop alternative osteoinductive molecular strategies that can effectively complement BMP activity to maximize biological efficiency while reducing BMP dose requirement. One alternative approach is to deliver small molecule compounds targeting osteoblast differentiation that can synergistically promote bone formation with BMPs.…”

Comparison of 5766 Vertebral Compression Fractures Treated With or Without Kyphoplasty

“…Second, any research using the NIS database cannot assess traditionally supported and validated outcome measures such as 30-day and 1-year mortality, pain scores, and outcome questionnaires (SF-36, Oswestry Disability Index, and others). This disadvantage has been surmounted by using previously described surrogate measures of functional outcome including in-hospital complications [3,5,10,11,33,52,53], in-hospital mortality [1,3,10,33,53], and patient disposition at hospital discharge [10,11,33,52,53]. Third, evidence is mounting to suggest patients who undergo kyphoplasty experience up to 36% higher risk of subsequent VCF resulting from the increased biomechanical stiffness of the treated vertebral body [22,29,45].…”

“…Other studies using the NIS database have considered the occurrence of in-hospital complications and mortality as a measure of the immediate and early outcome of a surgical intervention [1,3,5,10,17,18,33,36,52] or of the impact of a comorbidity or complication on outcome [11,53]. The lower rate of in-hospital mortality in patients treated with kyphoplasty suggests that, in our patient sample, kyphoplasty affects the restoration of independent functional mobility in a manner that leads to a lower likelihood of developing a life-threatening complication of treatment.…”

“…This database has been used to evaluate use trends and outcomes for a variety of procedures in spine surgery [1,5,10,15,20,26,28,33,36,47,52,59] as well as the impact of comorbidities on the outcome of spine procedures [3,11,17,18]. Such a database allows a larger patient sample to be amassed in relatively short period of time and for a lower cost than could be achieved by even a large multicenter trial; they also can offer insight into the actual use, complications, and outcomes of a procedure in ''real life'' and without the restrictive criteria imposed for inclusion in controlled trials.…”