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).

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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:

  1. 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)
  2. If this happens, you will definitely need IV antibiotics
  3. 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.

Fear Mongering?

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.

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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.



(1) Fujii K, Yamazaki M, Kang JD, Risbud MV, Cho SK, Qureshi SA, Hecht AC, Iatridis JC. Discogenic Back Pain: Literature Review of Definition, Diagnosis, and Treatment. JBMR Plus. 2019 Mar 4;3(5):e10180. doi: 10.1002/jbm4.10180. PMID: 31131347; PMCID: PMC6524679.

(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.

(3) Elabd C, Centeno CJ, Schultz JR, Lutz G, Ichim T, Silva FJ. Intra-discal injection of autologous, hypoxic cultured bone marrow-derived mesenchymal stem cells in five patients with chronic lower back pain: a long-term safety and feasibility study. J Transl Med. 2016 Sep 1;14(1):253. doi: 10.1186/s12967-016-1015-5. PMID: 27585696; PMCID: PMC5009698.

(4) Tuakli-Wosornu YA, Terry A, Boachie-Adjei K, Harrison JR, Gribbin CK, LaSalle EE, Nguyen JT, Solomon JL, Lutz GE. Lumbar Intradiskal Platelet-Rich Plasma (PRP) Injections: A Prospective, Double-Blind, Randomized Controlled Study. PM R. 2016 Jan;8(1):1-10; quiz 10. doi: 10.1016/j.pmrj.2015.08.010. Epub 2015 Aug 24. PMID: 26314234.

(5) Cheng J, Santiago KA, Nguyen JT, Solomon JL, Lutz GE. Treatment of symptomatic degenerative intervertebral discs with autologous platelet-rich plasma: follow-up at 5-9 years. Regen Med. 2019 Sep;14(9):831-840. doi: 10.2217/rme-2019-0040. Epub 2019 Aug 29. PMID: 31464577; PMCID: PMC6770415.

(6) Lutz C, Cheng J, Prysak M, Zukofsky T, Rothman R, Lutz G. Clinical outcomes following intradiscal injections of higher-concentration platelet-rich plasma in patients with chronic lumbar discogenic pain. Int Orthop. 2022 Jun;46(6):1381-1385. doi: 10.1007/s00264-022-05389-y. Epub 2022 Mar 28. PMID: 35344055; PMCID: PMC9117340.

(7) Jain D, Goyal T, Verma N, Paswan AK, Dubey RK. Intradiscal Platelet-Rich Plasma Injection for Discogenic Low Back Pain and Correlation with Platelet Concentration: A Prospective Clinical Trial. Pain Med. 2020 Nov 1;21(11):2719-2725. doi: 10.1093/pm/pnaa254. PMID: 32869064.

(8) Pettine KA, Suzuki RK, Sand TT, Murphy MB. Autologous bone marrow concentrate intradiscal injection for the treatment of degenerative disc disease with three-year follow-up. Int Orthop. 2017 Oct;41(10):2097-2103. doi: 10.1007/s00264-017-3560-9. Epub 2017 Jul 26. PMID: 28748380.

(9) Pettine K, Suzuki R, Sand T, Murphy M. Treatment of discogenic back pain with autologous bone marrow concentrate injection with minimum two year follow-up. Int Orthop. 2016 Jan;40(1):135-40. doi: 10.1007/s00264-015-2886-4. Epub 2015 Jul 10. PMID: 26156727.

(10) Pettine KA, Murphy MB, Suzuki RK, Sand TT. Percutaneous injection of autologous bone marrow concentrate cells significantly reduces lumbar discogenic pain through 12 months. Stem Cells. 2015 Jan;33(1):146-56. doi: 10.1002/stem.1845. PMID: 25187512.

(11) Wolff M, Shillington JM, Rathbone C, Piasecki SK, Barnes B. Injections of concentrated bone marrow aspirate as treatment for Discogenic pain: a retrospective analysis. BMC Musculoskelet Disord. 2020 Feb 28;21(1):135. doi: 10.1186/s12891-020-3126-7. PMID: 32111220; PMCID: PMC7049206.

(12) Atluri S, Murphy MB, Dragella R, Herrera J, Boachie-Adjei K, Bhati S, Manocha V, Boddu N, Yerramsetty P, Syed Z, Ganjam M, Jain D, Syed Z, Grandhi N, Manchikanti L. Evaluation of the Effectiveness of Autologous Bone Marrow Mesenchymal Stem Cells in the Treatment of Chronic Low Back Pain Due to Severe Lumbar Spinal Degeneration: A 12-Month, Open-Label, Prospective Controlled Trial. Pain Physician. 2022 Mar;25(2):193-207. PMID: 35322978.

(13) Papadimitriou N, Hebelka H, Hingert D, Baranto A, Barreto Henriksson H, Lindahl A, Brisby H. Intradiscal Injection of Iron-Labeled Autologous Mesenchymal Stromal Cells in Patients With Chronic Low Back Pain: A Feasibility Study With 2 Years Follow-Up. Int J Spine Surg. 2021 Dec;15(6):1201-1209. doi: 10.14444/8152. PMID: 35086878; PMCID: PMC9468939.

(14) Yavin D1, Casha S1, Wiebe S, Feasby TE, Clark C, Isaacs A, Holroyd-Leduc J, Hurlbert RJ, Quan H, Nataraj A, Sutherland GR, Jette N. Lumbar Fusion for Degenerative Disease: A Systematic Review and Meta-Analysis. Neurosurgery. 2017 May 1;80(5):701-715. doi: 10.1093/neuros/nyw162.

(15) Zaina F, Tomkins-Lane C, Carragee E, Negrini S. Surgical versus non-surgical treatment for lumbar spinal stenosis. Cochrane Database Syst Rev. 2016;2016(1):CD010264. Published 2016 Jan 29. doi:10.1002/14651858.CD010264.pub2

(16) Saavedra-Pozo FM, Deusdara RA, Benzel EC. Adjacent segment disease perspective and review of the literature. Ochsner J. 2014;14(1):78–83.

(17) Tobert DG, Antoci V, Patel SP, Saadat E, Bono CM. Adjacent Segment Disease in the Cervical and Lumbar Spine. Clin Spine Surg. 2017 Apr;30(3):94-101. doi: 10.1097/BSD.0000000000000442.

(18) Fraser RD, Osti OL, Vernon-Roberts B. Discitis after discography. J Bone Joint Surg Br. 1987 Jan;69(1):26-35. doi: 10.1302/0301-620X.69B1.3818728. PMID: 3818728.

(19) Pobiel RS, Schellhas KP, Pollei SR, Johnson BA, Golden MJ, Eklund JA. Diskography: infectious complications from a series of 12,634 cases. AJNR Am J Neuroradiol. 2006 Oct;27(9):1930-2. PMID: 17032869; PMCID: PMC7977892.

(20) Prysak MH, Lutz CG, Zukofsky TA, Katz JM, Everts PA, Lutz GE. Optimizing the safety of intradiscal platelet-rich plasma: an in vitro study with Cutibacterium acnes. Regen Med. 2019 Oct;14(10):955-967. doi: 10.2217/rme-2019-0098. Epub 2019 Oct 7. PMID: 31587600.

Chris Centeno, MD is a specialist in regenerative medicine and the new field of Interventional Orthopedics. Centeno pioneered orthopedic stem cell procedures in 2005 and is responsible for a large amount of the published research on stem cell use for orthopedic applications. View Profile

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NOTE: This blog post provides general information to help the reader better understand regenerative medicine, musculoskeletal health, and related subjects. All content provided in this blog, website, or any linked materials, including text, graphics, images, patient profiles, outcomes, and information, are not intended and should not be considered or used as a substitute for medical advice, diagnosis, or treatment. Please always consult with a professional and certified healthcare provider to discuss if a treatment is right for you.

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