European Spine Journal

, Volume 26, Issue 5, pp 1362–1373 | Cite as

ISSLS PRIZE IN BASIC SCIENCE 2017: Intervertebral disc/bone marrow cross-talk with Modic changes

  • Stefan Dudli
  • David C. Sing
  • Serena S. Hu
  • Sigurd H. Berven
  • Shane Burch
  • Vedat Deviren
  • Ivan Cheng
  • Bobby K. B. Tay
  • Todd F. Alamin
  • Ma Agnes Martinez Ith
  • Eric M. Pietras
  • Jeffrey C. Lotz
Original Article


Study design

Cross-sectional cohort analysis of patients with Modic Changes (MC).


Our goal was to characterize the molecular and cellular features of MC bone marrow and adjacent discs. We hypothesized that MC associate with biologic cross-talk between discs and bone marrow, the presence of which may have both diagnostic and therapeutic implications.

Background data

MC are vertebral bone marrow lesions that can be a diagnostic indicator for discogenic low back pain. Yet, the pathobiology of MC is largely unknown.


Patients with Modic type 1 or 2 changes (MC1, MC2) undergoing at least 2-level lumbar interbody fusion with one surgical level having MC and one without MC (control level). Two discs (MC, control) and two bone marrow aspirates (MC, control) were collected per patient. Marrow cellularity was analyzed using flow cytometry. Myelopoietic differentiation potential of bone marrow cells was quantified to gauge marrow function, as was the relative gene expression profiles of the marrow and disc cells. Disc/bone marrow cross-talk was assessed by comparing MC disc/bone marrow features relative to unaffected levels.


Thirteen MC1 and eleven MC2 patients were included. We observed pro-osteoclastic changes in MC2 discs, an inflammatory dysmyelopoiesis with fibrogenic changes in MC1 and MC2 marrow, and up-regulation of neurotrophic receptors in MC1 and MC2 bone marrow and discs.


Our data reveal a fibrogenic and pro-inflammatory cross-talk between MC bone marrow and adjacent discs. This provides insight into the pain generator at MC levels and informs novel therapeutic targets for treatment of MC-associated LBP.


Modic change Cross-talk Pathobiology Bone marrow Neurotrophic Inflammation Myelopoiesis Osteoclastogenesis Fibrosis Pain 



This study was supported by the Swiss National Science Foundation Grant 145961, 158792, and 164726 as well as the National Institutes of Health Grant AR063705.

Conflict of interest

None of the authors has any potential conflict of interest.

Supplementary material

586_2017_4955_MOESM1_ESM.docx (15 kb)
Supplementary material 1 (DOCX 14 kb)
586_2017_4955_MOESM2_ESM.doc (218 kb)
Supplementary material 2 (DOC 218 kb)
586_2017_4955_MOESM3_ESM.pdf (241 kb)
Supplementary material 3 (PDF 240 kb)


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Copyright information

© Springer-Verlag Berlin Heidelberg 2017

Authors and Affiliations

  • Stefan Dudli
    • 1
  • David C. Sing
    • 1
  • Serena S. Hu
    • 2
  • Sigurd H. Berven
    • 1
  • Shane Burch
    • 1
  • Vedat Deviren
    • 1
  • Ivan Cheng
    • 2
  • Bobby K. B. Tay
    • 1
  • Todd F. Alamin
    • 1
  • Ma Agnes Martinez Ith
    • 2
  • Eric M. Pietras
    • 3
  • Jeffrey C. Lotz
    • 1
  1. 1.Department of Orthopaedic SurgeryUniversity of California San FranciscoSan FranciscoUSA
  2. 2.Stanford Spine ClinicStanford University Medical CenterStanfordUSA
  3. 3.Division of HematologyUniversity of Colorado DenverDenverUSA

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