The Biological Enhancement of Spinal Fusion for Spinal Degenerative Disease

Abstract

In this era of aging societies, the number of elderly individuals who undergo spinal arthrodesis for various degenerative diseases is increasing. Poor bone quality and osteogenic ability in older patients, due to osteoporosis, often interfere with achieving bone fusion after spinal arthrodesis. Enhancement of bone fusion requires shifting bone homeostasis toward increased bone formation and reduced resorption. Several biological enhancement strategies of bone formation have been conducted in animal models of spinal arthrodesis and human clinical trials. Pharmacological agents for osteoporosis have also been shown to be effective in enhancing bone fusion. Cytokines, which activate bone formation, such as bone morphogenetic proteins, have already been clinically used to enhance bone fusion for spinal arthrodesis. Recently, stem cells have attracted considerable attention as a cell source of osteoblasts, promising effects in enhancing bone fusion. Drug delivery systems will also need to be further developed to assure the safe delivery of bone-enhancing agents to the site of spinal arthrodesis. Our aim in this review is to appraise the current state of knowledge and evidence regarding bone enhancement strategies for spinal fusion for degenerative spinal disorders, and to identify future directions for biological bone enhancement strategies, including pharmacological, cell and gene therapy approaches.

Role of oxidative metabolism in osseointegration during spinal fusion

“…Several biological enhancement strategies to promote successful spinal fusion have been proposed in animal and human clinical studies. These include use of bisphosphonates, teriparatide (recombinant deoxyribonucleic acid form of parathyroid hormone [PTH1-34]), prostaglandin agonists, bone morphogenic proteins (BMPs), and stem cells [ 25 ]. Among these, bone marrow stromal (a.k.a.…”

Editorial. Bisphosphonates do not impair spinal fusion

“…5 However, the effects of bisphosphonates on fusion success in these animal models are inconsistent, with some showing a negative effect and others no effect. 6,11 Unfortunately, this basic science work, along with the theoretical potential that uncoupling balanced osteoclastic and osteoblastic activity could adversely impact fusion, has caused some spine surgeons to be concerned about the perioperative use of this medication. Given the results of the current study by Guppy et al and the meta-analysis by Liu et al, 7 the concerns of a negative effect of bisphosphonate should be tempered.…”

Graft Materials and Biologics for Spinal Interbody Fusion

“…High doses of rhBMP-2 have also been loosely correlated with increased rates of deep infections (2.4%), arrhythmias (2.4%), cancer (3.4%), and pseudarthrosis (5%) in certain studies [48,60]. In an attempt to better alleviate risk of these complications, some studies with animal models suggest using parathyroid hormone (1-34) in addition to BMP to lessen the amount of BMP dosage required [61][62][63]. Finally, the cost of BMP is high according to one economic evaluation, and it may not be cost-effective for use in the majority of patients [64].…”