The Spine Journal 11 (2011) 107–108

Commentary

Something is amiss

Robert D. Fraser, MBBS, MD, FRACS*Spine Unit, Royal Adelaide Hospital, North Terrace, Adelaide SA 5000, Australia

Received 21 September 2010; accepted 23 September 2010

COMMENTARY ON: Cao P, Jiang L, Zhuang

DOI of original ar

FDA device/drug

Author disclosure

Spine; speaking/teach

Spine; fellowship sup

* Corresponding a

Terrace, Adelaide SA

8-8232-2792.

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1529-9430/$ - see fro

doi:10.1016/j.spinee.2

C, et al. Intradiscal injection therapy for degener-ative chronic discogenic low back pain with end plate Modic changes. Spine J 2011:11:100–6(in this issue).

Someone who has had no experience with a double-blindrandomized controlled trial (RCT) or who is not familiarwith the details of RCTs in the spinal literature may wellbe persuaded by the study of Cao et al. [1] that intradiscalsteroid is an effective treatment for patients with low backpain (LBP) and Modic Types 2 and 3 disc degeneration onmagnetic resonance imaging. However, to the discerningeye, the data from this study are most disturbing.

When have you seen a double-blind RCT with dramaticimprovement in outcome for the treatment group with nochange in the control or placebo group? The experience ofnumerous RCTs [2–9] on injection procedures for back painand sciatica shows that if the treatment group improves sowill the control group; it is a question of whether the differ-ence is significant. The improved outcome in control groupscan be attributed to a combination of natural history anda possible placebo effect [10]. In our double-blind RCT onchemonucleolysis, at 6 months, 57% of the control group(intradiscal saline) had improved compared with 80% ofthe group treated with intradiscal chymopapain [11]. Thetherapeutic benefit of chymopapain was, therefore, assessedas only 23%, which just reached significance, and the restwas attributed to natural history.

Apart from the Cao study, what other RCT has demon-strated such a dramatic improvement in outcome from aninjection procedure for chronic LBP? The claimed outcomefor intradiscal steroid is even superior to what is reported in

ticle: 10.1016/j.spinee.2010.07.001.

status: not applicable.

s: RDF (royalties, DePuy Spine; consulting, DePuy

ing arrangements, DePuy Spine; trips/travel, DePuy

port, DePuy Spine, Synthes).

uthor. Spine Unit, Royal Adelaide Hospital, North

5000, Australia. Tel.: (61) 8-8223-4067; fax: (61)

df@internode.on.net (R.D. Fraser)

nt matter � 2011 Elsevier Inc. All rights reserved.

010.09.016

numerous RCTs [12] on the treatment of sciatica, a condi-tion with more assistance from natural history than is thecase for chronic LBP.

When have you seen a double-blind RCT with such uni-form and tight data for baseline characteristics for all cohortsand for the respective outcomes for the treatment and controlgroups? The six cohorts of 20 patients had almost identicalmeans and ranges for age and baseline visual analog scaleand Oswestry Disability Index scores, almost identical sub-stantial improvements in outcome scores for the treatmentarms, and virtually no change in outcome scores for the con-trol arms. It would be miraculous if this occurred by chance.For a study that considered patients aged from 20 to 60 yearsfor enrollment, it seems odd that no patient in any of the sixcohorts was younger than 32 or older than 53 years.

The Cao study appears to have been undertaken to partlymimicKhot et al. [13], who carried out anRCT that comparedintradiscal steroid with intradiscal saline in patients withchronic LBP but with a shorter follow-up (6 months forCao et al. compared with 12 months for Khot et al.). Bothstudies had 120 participants who had failed to respond to 6weeks of conservative treatment; a single level for treatmentwas confirmed by discography; and the outcome was deter-mined by Oswestry Disability Index and visual analog scale.The Khot study had demonstrated no improvement at12 months in either the treatment or control groups, whichis in keeping with the overall disappointing experience withthe use of intradiscal steroid for chronic LBP [14]. It alsomirrored the outcome of our double-blind RCT assessingthe efficacy of intradiscal electrothermic therapy in patientswith continuous chronic LBP with no improvement eitherin the shamor treatment groups at 6months [15]. On the otherhand, the study by Cao et al. (which was handicapped byhaving the complexity of six cohorts of 20 patients) claimsa substantial benefit in the treatment of chronic LBP fromintradiscal steroid at 6 months.

108 R.D. Fraser / The Spine Journal 11 (2011) 107–108

Unfortunately, the article by Cao et al. provides no infor-mation on the length of the history of LBP, only that pa-tients failed to respond to 6 weeks of conservativetreatment and that they were unwilling to undergo surgery.Low back pain may be episodic or continuous; and the ep-isodic nature of LBP in some patients provides an explana-tion for improvement in a cohort at a given time point thatis independent of the treatment given. Hence, one possibleexplanation for the markedly different outcomes in the Caostudy would be if the control groups were made up of pa-tients with continuous pain, and the intradiscal steroidgroups consisted of patients with episodic pain; but thechance of this occurring with randomization seems remote.

At face value, the results of the study by Cao et al. indicateno difference in response for Modic Types 2 and 3 cohortsand no therapeutic benefit for adding polypeptides to intra-discal steroid. The authors conclude that intradiscal steroid‘‘could be a short-term efficient treatment for discogenicLBP.’’ As such, they seem to imply that intradiscal steroidcould be used repeatedly as a means of controlling pain inpatients with Modic end plate changes. Of considerableconcern is that they appear not to have used prophylacticantibiotic and, in fact, make no mention of the risk of iatro-genic discitis. Without antibiotic prophylaxis, there is a sig-nificant risk of disc space infection with any percutaneousdisc violation, up to 5% in one series of lumbar discogramscarried out by radiologists [16]. An animal study [17] hasdemonstrated that only a few bacteria are required to producethis painful and very disabling destructive process and thatboth intradiscal and intravenous antibiotic provides protec-tion [18,19]. Thus, the widespread use of intradiscal steroid,particularly if carried out repeatedly and without strict asep-tic technique and antibiotic prophylaxis, could be disastrous.

So how does one explain the data reported by Cao et al.that are so disparate from other RCTs on spinal disorders?There are three possibilities—the data may have occurredby chance, which seems most unlikely, the entry of patientsor collection of data may have been subject to bias, or theresults may have been tampered with. Whatever the cause,it would be quite inappropriate to develop treatment proto-cols based on this study.

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