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



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).


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).


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.


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.

This is a preview of subscription content, log in to check access.

Fig. 1


  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 17:1407–1422

    PubMed  Article  Google Scholar 

  2. 2.

    Albert HB, Manniche C (2007) Modic changes following lumbar disc herniation. Eur Spine J 16:977–982

    PubMed  Article  Google 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–S300

    PubMed  Article  Google Scholar 

  4. 4.

    Modic MT, Masaryk TJ, Ross JS, Carter JR (1988) Imaging of degenerative disk disease. Radiology 168:177–186

    PubMed  CAS  Google 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 166:193–199

    PubMed  CAS  Google 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 36:1236–1243

    PubMed  Article  Google 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 30:85–90

    PubMed  Article  Google 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 48:748–754

    PubMed  Article  CAS  Google 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 70:361–368

    PubMed  Article  CAS  Google Scholar 

  10. 10.

    Stirling A, Worthington T, Rafiq M, Lambert PA, Elliott TS (2001) Association between sciatica and Propionibacterium acnes. Lancet 357:2024–2025

    PubMed  Article  CAS  Google Scholar 

  11. 11.

    Stirling AJ, Jiggins M (2002) Association between Sciatica and Skin Commensals. International Society for the Study of the Lumbar Spine, Cleveland

    Google 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 meeting

  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–S46

    Article  Google 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 24:295–299

    PubMed  Google Scholar 

  15. 15.

    Roberts GJ, Holzel HS, Sury MR (1997) Dental bacteremia in children. Pediatr Cardiol 18:24–27

    PubMed  Article  CAS  Google Scholar 

  16. 16.

    Farrar MD, Ingham E (2004) Acne: inflammation. Clin Dermatol 22:380–384

    PubMed  Article  Google Scholar 

  17. 17.

    Doita M, Kanatani T, Harada T, Mizuno K (1996) Immunohistologic study of the ruptured intervertebral disc of the lumbar spine. Spine 21:235–241

    PubMed  Article  CAS  Google 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 15:1231–1233

    PubMed  Article  CAS  Google Scholar 

  19. 19.

    Ito T, Yamada M, Ikuta F et al (1996) Histologic evidence of absorption of sequestration-type herniated disc. Spine 21:230–234

    PubMed  Article  CAS  Google Scholar 

  20. 20.

    Lindblom K, Hultquist G (1950) Absorption of protruded disc tissue. J Bone Joint Surg 32:557–560

    PubMed  Google Scholar 

  21. 21.

    Gronblad M, Virri J, Tolonen J et al (1994) A controlled immunohistochemical study of inflammatory cells in disc herniation tissue. Spine 19:2744–2751

    PubMed  Article  CAS  Google 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 50:65–70

    PubMed  Article  CAS  Google 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)

  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 42:969–973

    PubMed  Article  CAS  Google 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 47:947–953

    PubMed  Article  CAS  Google 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 2:145–148

    PubMed  Article  CAS  Google 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]

    PubMed  Google 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 57:317–326

    PubMed  Article  CAS  Google 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 33:90–94

    PubMed  Article  Google 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 31:1026–1031

    PubMed  Article  Google 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 10:22

    PubMed  Article  Google 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–197S

    PubMed  Article  CAS  Google 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 50:1103–1110

    PubMed  Article  CAS  Google 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):81

    Article  Google Scholar 

  35. 35.

    Carragee EJ (1997) The clinical use of magnetic resonance imaging in pyogenic vertebral osteomyelitis. Spine 22:780–785

    PubMed  Article  CAS  Google 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 28:693–699

    PubMed  CAS  Google 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 29:1104–1110

    PubMed  Article  CAS  Google 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)

  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 16:353–358

    PubMed  Article  Google Scholar 

  40. 40.

    Møller Pedersen K, Wittrup-Jensen K, Brooks R, Gudex C (2003) Vaerdisaetning af sundhed. University of Southern Denmark Publishing, Odense, p 256

    Google 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 30:1887–1892

    PubMed  Article  Google Scholar 

Download references


Grant support was received from IMK general foundation, The Danish Rheumatism Association, Svend Hansen and Ina Hansens Foundation, Ib Henriksen Foundation, Dagmar Marshalls Foundation, Karen Hansen Memory Foundation, Ing. K.A. Rohde and Wife’s foundation. The funders had no role in the study design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, approval of, or decision to publish the manuscript. We would like to thank Alan Jordan Ph.D. for editorial assistance.

Conflict of interest


Author information



Corresponding author

Correspondence to Hanne B. Albert.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Albert, H.B., Sorensen, J.S., Christensen, B.S. et al. 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. Eur Spine J 22, 697–707 (2013).

Download citation


  • Modic changes
  • Antibiotics
  • Chronic low back pain
  • End plate changes
  • LBP