The New SIS Fact Finder Paper on Intradiscal Biologics
Is it safe to inject the intervertebral disc with orthobiologics? That’s the topic taken up by the Spinal Intervention Society (SIS) in a recent paper published by their Patient Safety Committee. After reading this paper, I have to say that I agree with some of the caution, but I also recognize that there is a tiny bit of fear-mongering here. Let me explain.
Injecting the Intervertebral Disc
We know that the intervertebral disc can cause pain (1). The concept behind injecting and pressurizing the disc to identify if the disc is causing pain (discography) or to reduce low back pain caused by the disc isn’t new. The rationale for treating the disc through injection is that if the disc pain is disabling, more invasive treatments like lumbar fusion surgery are often recommended. This is a procedure with considerable morbidity where the efficacy has been questioned, so avoiding it is just smart medicine (14-16).
The Research on Autologous Orthobiologics to Treat Disc Pain or DDD
There has been a steady stream of research on injecting orthobiologics intradiscal. I’m pretty certain that I was the first physician on earth to inject stem cells into a low back disc back in approximately 2006. Since then, I’ve published several papers on this topic using culture-expanded mesenchymal stem cells (2,3). That technology is now part of an FDA IND and phase 2 clinical trial.
The idea behind using orthobiologics like platelet-rich plasma (PRP), bone marrow concentrate (BMC), or culture-expanded mesenchymal stem cells to reduce low back pain is that these injections may help repair the disc and thus reduce chronic low back pain. Hence, first, let’s try to answer how much research we have that this approach works.
The use of PRP injected into the disc has been the subject of several studies. Lutz et al. have published several papers on leukocyte-rich PRP (LR-PRP) injected into the discs of DDD patients with excellent results compared to placebo saline injections (4,5). That procedure has since been optimized further by substituting higher-dose PRP (6). The idea that a higher platelet concentration leads to better clinical results was also reported by Jain et al. (7).
Bone Marrow Concentrate, or BMC, is created by isolating the fraction of bone marrow aspirate containing mesenchymal stem cells. The research on injecting BMC into low back discs goes back a number of years and was first published by Pettine et al. This response depended on the number of cells delivered, meaning the patients injected with a higher number of stem cells (as determined by CFU-f) reported superior outcomes (8-10). Wolff et al. have also reported solid clinical results using BMC injected into lumbar discs (11). Finally, Atluri et al. reported excellent results using disc and functional spinal unit injections with BMC (12).
The outcome of intradiscal injection of culture-expanded mesenchymal stem cells has also been reported in the literature (13). Our group has also published positive case series results using culture-expanded cells (2,3).
It should also be noted that several companies have been in FDA clinical trials to get approval for allogeneic cell therapy products injected into the intervertebral disc to treat DDD. I have blogged on that topic recently.
In summary, there is an expanding research base for injecting the intervertebral disc to help chronic low back pain patients. The best evidence to date is for PRP, with bone marrow concentrate gaining research support. More research is always better than less, so more is needed. However, on today’s topic, none of these papers discuss any serious safety concerns with these treatments.
The New SIS Report on Intradiscal Orthobiologics
The Spinal Interventional Society (SIS) recently published one of its many “FactFinders” reports on the safety of interventional spine procedures. This was entitled “Complications from Intradiscal Biologic Intervention.” As I reviewed above, the SIS panel that authored this report both brings up a critical point and, IMHO, fearmongers just a little bit. So let’s delve into both the positives and negatives.
Are there any Experts in Intradiscal Orthobiologics on this Panel?
Since this is a panel about the specific topic of intradiscal orthobiologics, it would seem reasonable to include one or more published authors who have performed original clinical research in this area. I searched all of the physicians’ names in the panel and didn’t find any hits on the US National Library of Medicine showing clinical research on this topic. That’s concerning.
What Does the Report Focus On?
The SIS report focuses on the complication of discitis, which is a genuine concern for every patient considering any injection into the intervertebral disc. That means that there is bacterial overgrowth inside the disc, which can destroy the surrounding tissues. I agree with the study authors that this is often NOT discussed with patients signing up for intradiscal orthobiologic injections in a real and verifiable way. Hence many enter into these procedures uninformed or poorly informed of the risks.
I also agree that this requires expanded informed consent. This is what I tell patients:
- There is a 1 in 200 or less chance of discitis (when using a two-needle technique-some papers show less prevalence, but I always use the higher number) (18,19)
- If this happens, you will definitely need IV antibiotics
- You may also need surgery to clean out the disc
I find that about 2/3rds or more at that point don’t want me to inject the disc.
Is publishing this paper fear-mongering? On the one hand, as I have discussed above, this is a real problem. However, what is the real risk of discitis versus complications from alternative procedures? The biggest competitor procedure would be a lumbar fusion. So let’s compare these two options in terms of risk to the patient with low back pain:
- Orthobiologioc Injection-0.5% chance of discitis
- Fusion-A serious complication rate of 10-24% with 20% of patients with ASD at five years (15, 17)
It’s pretty clear that even with the risk of discitis, the rate of complications of fusion is about 20X an intradiscal injection.Join us for a free Regenexx webinar.
Can the risk of Discitis be Reduced by What You Inject?
Our science team and others have worked with Greg Lutz out of HSS and looked at the influence of either leukocyte-poor (LP-PRP) or leukocyte-rich PRP (LR-PRP) on one of the most common bacteria involved in discitis (20). Basically, LR-PRP with a small amount of gentamycin antibiotic added worked in the lab to kill this bacteria successfully. How that impacts the true rate of discitis in actual patients remains to be seen.
The upshot? The risk of discitis in the use of intradiscal orthobiologics is very real. Having said that, when considering the alternatives, the risk of a serious complication with fusion is at least 20 times higher. In the end analysis, I applaud SIS for reminding us that we must inform patients undergoing these procedures about this potential complication.
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(2) Centeno C, Markle J, Dodson E, Stemper I, Williams CJ, Hyzy M, Ichim T, Freeman M. Treatment of lumbar degenerative disc disease-associated radicular pain with culture-expanded autologous mesenchymal stem cells: a pilot study on safety and efficacy. J Transl Med. 2017 Sep 22;15(1):197. doi: 10.1186/s12967-017-1300-y. PMID: 28938891; PMCID: PMC5610473.
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