Clean teeth, bad back? Antibiotics for chronic low back pain.

It is unsurprising that there are few-to-no impressively effective treatments for chronic non-specific low back pain. The clue is in the “diagnostic” label. Non-specific low back pain represents the vast majority of cases for whom our traditional diagnoses don’t explain a great deal. If we can’t put our finger on what is causing it, we are likely to be donkeys at treating it.

There is much discussion and debate about why things are this way. Some argue that, at least in chronic persistent cases, the reason that imaging findings correlate poorly with symptoms and outcome is because these factors are no longer driving the symptoms. Rather, features such as central sensitization and a complex interaction of psychosocial factors drive the syndrome, causing on-going pain and disability in the absence of a continuing cause in the spinal tissues. Others that our imaging technologies and research designs simply lack the sophistication to finger the real culprit in the tissues. We’ve covered this ground before (see here).  Playing out in the middle of this conceptual minefield for a while now have been Modic changes.

Modic changes are found on spinal MRI scans around the borders of the disc and vertebral body. They seem easy to spot and, unlike most MRI findings in the spine, do seem to be consistently associated with the presence of non-specific low back pain and may have some prognostic influence. They are understood to represent bone oedema (swelling) and it is suggested that the cause might be infection with bacteria that normally live in your mouth. Curiously the obvious pathway for these bacteria to your disc is via the bloodstream, most likely via brushing your teeth.  This suggestion is lent weight by the finding of such bacteria, particularly the delightful sounding Proprionibacterium acnes (p acnes), more frequently in the nuclear material of patients with disc herniations who then went on to develop new Modic changes in adjacent vertebrae. Could it really be so simple – that for this group of patients antibiotics might offer an answer?

A trial just published in the European Spine Journal sought to test this. Following from some promising uncontrolled exploratory findings they took a group of patients with chronic back pain, who had had a finding of disc herniation on MRI within the preceding 6 to 24 months and gave them a repeat MRI. It is worth noting that these were not all non-specific cases, they included patients with or without neuropathic pain and some who had undergone spinal surgery. Those who demonstrated new Modic (Type I – the smallest type) changes adjacent to that disc were recruited and randomised to a 100-day course of high-dose oral antibiotic therapy or placebo and followed for a year. The design was nice and tight: good randomisation, allocation concealment and blinding of all the key players.

The findings are, at first glance, remarkable. Statistically significant improvements seen at the end of treatment, but further, larger and clinically important improvements were observed at one year.  This was as predicted – at 100 days the underlying infection may have gone but at one year there has been time for substantial biological repair. The results show a 45% reduction in back pain at one year versus no reduction in the placebo group, and a 53% improvement in disability versus a 7% reduction in the placebo group. More surprisingly they found a 68% reduction in leg pain versus a slight increase in the placebo group. For chronic back pain these are genuinely eye-catching numbers and were accompanied with improvements in Modic changes on MRI. There was a price though, adverse events, mostly gastro-enterological and varying in severity were much more prevalent in the group taking antibiotics.

There are, in my view, reasons to be cautious here. The approach taken to the analysis seems a little basic. Worse the analysis does not appear to have employed a genuine “intention to treat” approach, or, if it did, it is not clear how. This is important as it helps to prevent uneven drop-out of participants during the trial from artificially inflating the effects. 14% of participants dropped out of the active arm compared to 7% in the placebo arm. This probably doesn’t catastrophically undermine the results of the trial but it offers a path by which the size might have been exaggerated. I find this a shame because it is so easy (and standard practice) to fix and its absence muddies the waters of what is otherwise an exciting finding. Finally there is an almost total lack of a response in the placebo group suggesting no impact of placebo effects, natural recovery or regression to the mean. Which is odd.

What these results don’t do is offer us a solution to the broad problem CNSLBP. The group in this trial were, quite correctly, very carefully selected by the probability that Modic changes might explain their pain. This type of selection is likely to have preferentially recruited many patients who we would not consider to be “non-specific”.  But they do seem to suggest that a proportion of cases could be chipped away from the non-specificity mountain and be offered a substantially effective treatment. Before we jump on that bandwagon with both feet, let’s have a big, multi-centre trial with a nice, tight approach to data analysis. In the meantime it’s interesting to ponder whether population- level leaps forward in oral hygiene may have surreptitiously fed an explosion in disabling chronic low back pain.

Neil O’Connell

Neil OConnellAs well as writing for Body in Mind, Dr Neil O’Connell, (PhD, not MD) is a researcher in the Centre for Research in Rehabilitation, Brunel University, West London, UK. He divides his time between research and training new physiotherapists and previously worked extensively as a musculoskeletal physiotherapist.

He also tweets! @NeilOConnell

Neil’s main research interests are chronic low back pain and chronic pain more broadly with a focus on evidence based practice. He has conducted numerous systematic reviews including some for the Cochrane Collaboration. He also makes a mean Yorkshire pudding despite being a child of Essex.

Link to Neil’s published research here. Downloadable PDFs here

References

Jensen TS, Karppinen J, Sorensen JS, Niinimäki J, & Leboeuf-Yde C (2008). Vertebral endplate signal changes (Modic change): a systematic literature review of prevalence and association with non-specific low back pain. Eur Spine J, 17 (11), 1407-22 PMID: 18787845

Jensen RK, Leboeuf-Yde C, Wedderkopp N, Sorensen JS, Jensen TS, & Manniche C (2012). Is the development of Modic changes associated with clinical symptoms? A 14-month cohort study with MRI. Eur Spine J, 21 (11), 2271-9 PMID: 22526703

Albert HB, Lambert P, Rollason J, Sorensen JS, Worthington T, Pedersen MB, Nørgaard HS, Vernallis A, Busch F, Manniche C, & Elliott T (2013). Does nuclear tissue infected with bacteria following disc herniations lead to Modic changes in the adjacent vertebrae? Eur Spine J PMID: 23397187

Albert HB, Sorensen JS, Christensen BS, & Manniche C (2013). Antibiotic treatment in patients with chronic low back pain and vertebral bone edema (Modic type 1 changes): a double-blind randomized clinical controlled trial of efficacy. Euro Spine J PMID: 23404353

Albert HB, Manniche C, Sorensen JS, & Deleuran BW (2008). Antibiotic treatment in patients with low-back pain associated with Modic changes Type 1 (bone oedema): a pilot study. Br J Sports Med, 42 (12), 969-73 PMID: 18718972