European Spine Journal

, Volume 22, Issue 4, pp 697–707

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

  • Hanne B. Albert
  • Joan S. Sorensen
  • Berit Schiott Christensen
  • Claus Manniche
Original Article

Abstract

Purpose

Modic type 1 changes/bone edema in the vertebrae are present in 6 % of the general population and 35–40 % of the low back pain population. It is strongly associated with low back pain. The aim was to test the efficacy of antibiotic treatment in patients with chronic low back pain (>6 months) and Modic type 1 changes (bone edema).

Methods

The study was a double-blind RCT with 162 patients whose only known illness was chronic LBP of greater than 6 months duration occurring after a previous disc herniation and who also had bone edema demonstrated as Modic type 1 changes in the vertebrae adjacent to the previous herniation. Patients were randomized to either 100 days of antibiotic treatment (Bioclavid) or placebo and were blindly evaluated at baseline, end of treatment and at 1-year follow-up.

Outcome measures

Primary outcome, disease-specific disability, lumbar pain. Secondary outcome leg pain, number of hours with pain last 4 weeks, global perceived health, EQ-5D thermometer, days with sick leave, bothersomeness, constant pain, magnetic resonance image (MRI).

Results

144 of the 162 original patients were evaluated at 1-year follow-up. The two groups were similar at baseline. The antibiotic group improved highly statistically significantly on all outcome measures and improvement continued from 100 days follow-up until 1-year follow-up. At baseline, 100 days follow-up, 1-year follow-up the disease-specific disability-RMDQ changed: antibiotic 15, 11, 5.7; placebo 15, 14, 14. Leg pain: antibiotics 5.3, 3.0, 1.4; placebo 4.0, 4.3, 4.3. Lumbar pain: antibiotics 6.7, 5.0, 3.7; placebo 6.3, 6.3, 6.3. For the outcome measures, where a clinically important effect size was defined, improvements exceeded the thresholds, and a trend towards a dose–response relationship with double dose antibiotics being more efficacious.

Conclusions

The antibiotic protocol in this study was significantly more effective for this group of patients (CLBP associated with Modic I) than placebo in all the primary and secondary outcomes.

Keywords

Modic changes Antibiotics Chronic low back pain End plate changes LBP 

References

  1. 1.
    Jensen TS, Karppinen J, Sorensen JS, Niinimäki J, Leboeuf-Yde C (2008) Prevalence of vertebral endplate signal (Modic) changes and their association with non-specific low back pain—A systematic literature review. Eur Spine J 17:1407–1422PubMedCrossRefGoogle Scholar
  2. 2.
    Albert HB, Manniche C (2007) Modic changes following lumbar disc herniation. Eur Spine J 16:977–982PubMedCrossRefGoogle Scholar
  3. 3.
    Airaksinen O, Brox JI, Cedraschi C et al (2006) European guidelines: COST B13 working group on guidelines for chronic low back pain. Eur Spine J 15(Suppl 2):S192–S300PubMedCrossRefGoogle Scholar
  4. 4.
    Modic MT, Masaryk TJ, Ross JS, Carter JR (1988) Imaging of degenerative disk disease. Radiology 168:177–186PubMedGoogle Scholar
  5. 5.
    Modic MT, Steinberg PM, Ross JS, Masaryk TJ, Carter JR (1988) Degenerative disk disease: assessment of changes in vertebral body marrow with MR imaging. Radiology 166:193–199PubMedGoogle Scholar
  6. 6.
    Wang Y, Videman T, Niemeläinen R, Battié MC (2011) Quantitative measures of Modic changes in lumbar spine magnetic resonance imaging: intra- and inter-rater reliability. Spine 36:1236–1243PubMedCrossRefGoogle Scholar
  7. 7.
    Peterson CK, Gatterman B, Carter JC, Humphreys BK, Weibel A (2007) Inter- and intraexaminer reliability in identifying and classifying degenerative marrow (Modic) changes on lumbar spine magnetic resonance scans. J Manipulative Physiol Ther 30:85–90PubMedCrossRefGoogle Scholar
  8. 8.
    Jensen TS, Sorensen JS, Kjaer P (2007) Intra- and interobserver reproducibility of vertebral endplate signal (modic) changes in the lumbar spine: the Nordic Modic Consensus Group classification. Acta Radiol 48:748–754PubMedCrossRefGoogle Scholar
  9. 9.
    Albert HB, Kjaer P, Jensen TS, Sorensen JS, Bendix T, Manniche C (2008) Modic changes, possible causes and relation to low back pain. Med Hypotheses 70:361–368PubMedCrossRefGoogle Scholar
  10. 10.
    Stirling A, Worthington T, Rafiq M, Lambert PA, Elliott TS (2001) Association between sciatica and Propionibacterium acnes. Lancet 357:2024–2025PubMedCrossRefGoogle Scholar
  11. 11.
    Stirling AJ, Jiggins M (2002) Association between Sciatica and Skin Commensals. International Society for the Study of the Lumbar Spine, ClevelandGoogle Scholar
  12. 12.
    Corsia MF, Wack M, Denys G (2003) Low vitulence Bacterial infections of intervertebral discs and the resultant spinal disease processes. Abstract from Scoliosis Research Society (SRS) annual meetingGoogle Scholar
  13. 13.
    Agarwal VJ, Golish R, Kondrashov D, Alamin TF (2010) Results of bacterial culture from surgically excised intervertebral disc in 52 patients undergoing primary lumbar disc microdiscectomy at a single level. Spine J 10:S45–S46CrossRefGoogle Scholar
  14. 14.
    Bhanji S, Williams B, Sheller B, Elwood T, Mancl L (2002) Transient bacteremia induced by tooth brushing a comparison of the Sonicare toothbrush with a conventional toothbrush. Pediatr Dent 24:295–299PubMedGoogle Scholar
  15. 15.
    Roberts GJ, Holzel HS, Sury MR (1997) Dental bacteremia in children. Pediatr Cardiol 18:24–27PubMedCrossRefGoogle Scholar
  16. 16.
    Farrar MD, Ingham E (2004) Acne: inflammation. Clin Dermatol 22:380–384PubMedCrossRefGoogle Scholar
  17. 17.
    Doita M, Kanatani T, Harada T, Mizuno K (1996) Immunohistologic study of the ruptured intervertebral disc of the lumbar spine. Spine 21:235–241PubMedCrossRefGoogle Scholar
  18. 18.
    Hirabayashi S, Kumano K, Tsuiki T, Eguchi M, Ikeda S (1990) A dorsally displaced free fragment of lumbar disc herniation and its interesting histologic findings. A case report. Spine 15:1231–1233PubMedCrossRefGoogle Scholar
  19. 19.
    Ito T, Yamada M, Ikuta F et al (1996) Histologic evidence of absorption of sequestration-type herniated disc. Spine 21:230–234PubMedCrossRefGoogle Scholar
  20. 20.
    Lindblom K, Hultquist G (1950) Absorption of protruded disc tissue. J Bone Joint Surg 32:557–560PubMedGoogle Scholar
  21. 21.
    Gronblad M, Virri J, Tolonen J et al (1994) A controlled immunohistochemical study of inflammatory cells in disc herniation tissue. Spine 19:2744–2751PubMedCrossRefGoogle Scholar
  22. 22.
    Wedderkopp N, Thomsen K, Manniche C, Kolmos HJ, Secher Jensen T, Leboeuf Yde C (2009) No evidence for presence of bacteria in Modic type I changes. Acta Radiol 50:65–70PubMedCrossRefGoogle Scholar
  23. 23.
    Albert HB, Rollason J, Lambert P et al. Is the herniated nucleus material in lumbar disc herniations infected with bacteria, and does the infection cause Modic changes in the surrounding vertebrae? (Submitted to European Spine)Google Scholar
  24. 24.
    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 42:969–973PubMedCrossRefGoogle Scholar
  25. 25.
    Solgaard Sorensen J, Kjaer P, Jensen ST, Andersen P (2006) Low-field magnetic resonance imaging of the lumbar spine: reliability of qualitative evaluation of disc and muscle parameters. Acta Radiol 47:947–953PubMedCrossRefGoogle Scholar
  26. 26.
    Housden PL, Sullivan MF (1993) Do augmentin or cefuroxime reach effective levels in lumbar vertebral discs when used prophylactically for discectomy? A preliminary report. Eur Spine J 2:145–148PubMedCrossRefGoogle Scholar
  27. 27.
    Albert HB, Jensen AM, Dahl D et al (2003) Criteria validation of the Roland Morris questionnaire. A Danish translation of the international scale for the assessment of functional level in patients with low back pain and sciatica. Ugeskr Laeger 165:1875–1880 [in Danish]PubMedGoogle Scholar
  28. 28.
    Manniche C, Asmussen K, Lauritsen B et al (1994) Low back pain rating scale: validation of a tool for assessment of low back pain. Pain 57:317–326PubMedCrossRefGoogle Scholar
  29. 29.
    Ostelo RW, Deyo RA, Stratford P et al (2008) Interpreting change scores for pain and functional status in low back pain towards international consensus regarding minimal important change. Spine 33:90–94PubMedCrossRefGoogle Scholar
  30. 30.
    Ohtori S, Inoue G, Ito T, Koshi T et al (2006) Tumor necrosis factor-immunoreactive cells and PGP 9.5-immunoreactive nerve fibers in vertebral endplates of patients with discogenic low back Pain and Modic Type 1 or Type 2 changes on MRI. Spine 31:1026–1031PubMedCrossRefGoogle Scholar
  31. 31.
    Jensen RK, Leboeuf-Yde C, Wedderkopp N, Sorensen JS, Manniche C (2012) Rest versus exercise as treatment for patients with low back pain and Modic changes. A randomized controlled clinical trial. BMC Med 10:22PubMedCrossRefGoogle Scholar
  32. 32.
    Hahm KB, Lee KJ, Kim YS et al (1998) Quantitative and qualitative usefulness of reamipide in eradication regimen of Helicobacter pylori. Dig Dis Sci 43:192S–197SPubMedCrossRefGoogle Scholar
  33. 33.
    Ziegeler S, Raddatz A, Hoff G et al (2006) Antibiotics modulate the stimulated cytokine response to endotoxin in a human ex vivo, in vitro model. Acta Anaesthesiol Scand 50:1103–1110PubMedCrossRefGoogle Scholar
  34. 34.
    Jensen TS, Bendix T, Sorensen JS, Manniche C, Korsholm L, Kjaer P (2009) Characteristics and natural course of vertebral endplate signal (Modic) changes in the Danish general population. BMC Musculoskelet Disord 3(10):81CrossRefGoogle Scholar
  35. 35.
    Carragee EJ (1997) The clinical use of magnetic resonance imaging in pyogenic vertebral osteomyelitis. Spine 22:780–785PubMedCrossRefGoogle Scholar
  36. 36.
    Kowalski TJ, Layton KF, Berbari EF, Steckelberg JM, Huddleston PM, Wald JT, Osmon DRAJNR (2007) Follow-up MR imaging in patients with pyogenic spine infections: lack of correlation with clinical features. Am J Neuroradiol 28:693–699PubMedGoogle Scholar
  37. 37.
    Hsu CY, Yu CW, Wu MZ, Chen BB, Huang KM, Shih TT (2008) Unusual manifestations of vertebral osteomyelitis: intraosseous lesions mimicking metastases. AJNR Am J Neuroradiol 29:1104–1110PubMedCrossRefGoogle Scholar
  38. 38.
    Boesen M, Kubassova O, Bouert R, Axelsen MB, Ostergaard M, Cimmino MA, Danneskiold-Samsøe B, Hørslev-Petersen K, Bliddal H (2011) Correlation between computer-aided dynamic gadolinium-enhanced MRI assessment of inflammation and semi-quantitative synovitis and bone marrow oedema scores of the wrist in patients with rheumatoid arthritis–a cohort study. Rheumatology (epub ahead)Google Scholar
  39. 39.
    Uçkay I, Dinh A, Vauthey L, Asseray N, Passuti N, Rottman M, Biziragusenyuka J, Riché A, Rohner P, Wendling D, Mammou S, Stern R, Hoffmeyer P, Bernard L (2010) Spondylodiscitis due to Propionibacterium acnes: report of twenty-nine cases and a review of the literature. Clin Microbiol Infect 16:353–358PubMedCrossRefGoogle Scholar
  40. 40.
    Møller Pedersen K, Wittrup-Jensen K, Brooks R, Gudex C (2003) Vaerdisaetning af sundhed. University of Southern Denmark Publishing, Odense, p 256Google Scholar
  41. 41.
    Dunn KM, Croft PR (2005) Classification of low back pain in primary care: using “bothersomeness” to identify the most severe cases. Spine 30:1887–1892PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Hanne B. Albert
    • 1
  • Joan S. Sorensen
    • 1
  • Berit Schiott Christensen
    • 2
  • Claus Manniche
    • 1
  1. 1.Research Department, Spine Centre of Southern Denmark, Institute of Regional Health Services Research, Lillebaelt HospitalUniversity of Southern DenmarkMiddelfartDenmark
  2. 2.Department of RheumatologyAarhus University HospitalAarhusDenmark

Personalised recommendations