Annotated Bibliography, March 2015

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1. Perilli E, Parkinson IH, Truong L-H, Chong KC, Fazzalari NL, Osti OL. Modic (endplate) changes in the lumbar spine: bone micro-architecture and remodelling. Eur Spine J. 2014. doi:10.1007/s00586-014-3455-z.

The authors characterize the bone micro-architectural parameters and bone-remodeling indices associated with Modic endplate changes. The study group consisted of 40 patients suffering from disabling low back pain who were undergoing elective spinal surgery, and exhibiting Modic changes on MRI (Modic 1, n = 9; Modic 2, n = 25; Modic 3, n = 6). The patients underwent transpedicular vertebral body biopsy of the subchondral bone using an 8G Jamshidi needle. Biopsies were examined by micro-CT, for 3D morphometric analysis of bone volume fraction, trabecular thickness, trabecular separation and trabecular number. Samples also underwent histological analysis, for determination of bone remodeling indices: osteoid surface to bone surface ratio. Modic type 1 endplate biopsies had evidence of highest bone turnover, thought related to an inflammatory process; Modic 2 endplate biopsies were consistent with a reduced bone formation/remodelling stage and Modic 3 endplates showed a more stable sclerotic phase, with significantly increased bone volume fraction.

From the beginning of the description of these endplate changes, our assumption has been that the type I changes reflected a more acute phase, since these endplates were seen in patients who had undergone recent disc surgery where the instrumentation of the disc had accelerated degeneration, and in patients who received chymopapain injections (which is a model for acute disc degeneration). The type II endplates, aka “fatty endplates”, we viewed as a more chonic condition (and potentially more “stable”) since they could be seen in patients after successful lumbar fusion, and even in patients after successful treatment of a disc space infection where the disc space goes on to fuse. Type III we considered as the endstage, equivalent to discogenic sclerosis with a large amount of bone production. It is gratifying to see real data, as in this paper, that puts some weight behind our general impressions of the etiology of these signal changes.


2. El Barzouhi A, Vleggeert-Lankamp CL a M, van der Kallen BF, et al. Back pain’s association with vertebral end-plate signal changes in sciatica. Spine J. 2014;14(2):225–33. doi:10.1016/j.spinee.2013.08.058.

Patients with 6-12 weeks of sciatica, were enrolled in a multicenter, randomized clinical trial comparing early surgery strategy with prolonged conservative care with surgery if needed. Of the 168 patients who received surgery, 50 developed type I endplates at the one-year follow-up. Undergoing surgery for sciatica was highly associated with the development of endplate changes. However, both at baseline and after 1 year, those with and those without endplate changes reported disabling back pain in the same proportion. The authors conclude that the results show that endplate changes are not responsible for disabling low back pain in patients with sciatica and one should be reticent to offer back surgery based on MRI end-plate changes.

The authors seem to be equating LBP in the acute postoperative population to low back pain in the chronic nonoperated group. You commonly see new type I changes in patients who have had a discectomy within the past 4-6 months, which I have always ascribed to iatrogenic acute disc degeneration. This acute change may be quite a different pathology (such as edema) compared to chronic type I change (with replacement of normal hematopoietic marrow with fibrovascular marrow).


3. Sheng-Yun L, Letu S, Jian C, et al. Comparison of Modic Changes in the Lumbar and Cervical Spine, in 3167 Patients with and without Spinal Pain. PLoS One. 2014;9(12):e114993. doi:10.1371/journal.pone.0114993.

Retrospective clinical survey comparing the prevalence of Modic changes in the cervical and lumbar spine. MRs were compared from five patient groups: 1) 1223 patients with low-back pain/radiculopathy only; 2) 1023 patients with neck pain/radiculopathy only; 3) 497 patients with concurrent low-back and neck symptoms; 4) 304 asymptomatic subjects with lumbar MRIs; and 5) 120 asymptomatic subjects with cervical MRIs. The prevalence of endplate changes was higher in those with spinal pain than in those without, both in the lumbar spine (21.0% vs. 10.5%) and cervical spine (8.8% vs. 3.3%). Type II changes were most common. The prevalence of lumbar and cervical MCs increased with age, disc degeneration, (descending) spinal level, and increased kyphosis.

This adds to the large literature describing the prevalence of these changes, with by far the most common type being the fatty endplates (type II). In the initial paper by Modic (Radiology 1988; 166:193-199) we the relative percentages of endplate changes out of 474 MR’s was 4% type I, 16% type 2. Type III were the least common.


4. Fields AJ, Liebenberg EC, Lotz JC. Innervation of pathologies in the lumbar vertebral end plate and intervertebral disc. Spine J. 2014;14(3):513–21. doi:10.1016/j.spinee.2013.06.075.

The authors evaluated 92 end plates and 46 intervertebral discs from seven cadaver spines. Prior to dissection, the spines were scanned with MR to grade for Modic changes and high-intensity zones. Standard immunohistochemical techniques were used to localize the general nerve marker protein gene product 9.5. They quantified innervation in fibrovascular endplate marrow, fatty endplate marrow, endplate defects, and annular tears. Nerves were present in the majority of end plates with fibrovascular marrow, fatty marrow, and defects. Nerve density was significantly higher in fibrovascular endplate marrow than in normal endplate marrow. They conclude that vertebral endplate pathologies are more innervated than intervertebral disc pathologies and many innervated endplate pathologies are not detectable on MR.

An important paper, I think, that refocuses our attention away from the annulus and towards the endplate as the potential pain generator.


5. Fayad F, Lefevre-Colau M-M, Rannou F, et al. Relation of inflammatory Modic changes to intradiscal steroid injection outcome in chronic low back pain. Eur Spine J. 2007;16(7):925–31. doi:10.1007/s00586-006-0301-y.

The purpose of this manuscript was to analyze the association between the severity of inflammatory endplate changes (Modic) on MRI and the clinical response to intradiscal injection of steroids in chronic low back pain. 74 patients with LBP and inflammatory Modic changes which showed no response to 3-month conservative treatment received lumbar steroid injections. Outcome was the change in LBP intensity between baseline and 1 month after the steroid injection, as measured by VAS. At 1 month, the pain reduction was higher in the type I and mixed I/II endplates than in the pure fatty endplate group. They conclude that intradiscal injection of corticosteroids could be a short-term efficient treatment for patients with chronic LBP and predominantly inflammatory endplate changes.

An overall rather weak recommendation for the use of intradiscal steroids given the short-term benefit. This course of action would seem to make sense given the current thoughts on endplate changes, with their increase in pro-inflammatory mediators such as TNF and IL-6.


6. Beaudreuil J, Dieude P, Poiraudeau S, Revel M. Disabling chronic low back pain with Modic type 1 MRI signal: acute reduction in pain with intradiscal corticotherapy. Ann Phys Rehabil Med. 2012;55(3):139–47. doi:10.1016/

The underlying theory is that Modic type 1 changes may reflect inflammatory reaction in bone marrow adjacent to vertebral end plates and the intervertebral disc that is undergoing an active degenerative process. This was a retrospective study of data from medical records from 1995-1998. During 3-day hospitalization, patients underwent discography, and then received one injection of methylprednisolone (2 ml; Solu-Medrol) into the center of the disc. Patients were asked to remain in bed for 12-24 hours and to wear lumbar support for 2 weeks. Cohorts were defined as Modic I-a, if patients had Modic type 1 changes with no previous surgery or nucleolysis (n = 30); Modic I-b, if patients had Modic type 1 changes at the level of previous surgery or nucleolysis (n = 37); Control, if patients had no Modic type 1 changes (n = 30). 24 hours after steroid injection, a higher proportion of patients with self-assessed improvement was observed in Modic I-a (90%) and Modic I-b (71%) groups than in the control (30%) group. Low back pain decreased in both Modic groups. Low back pain did not vary from baseline in controls. The authors conclude that patients with disabling chronic low back pain and Modic type 1 MRI changes have specific acute response to intradiscal injection of methylprednisolone.

Interesting study using old data, which could not be reproduced today, since they had a 3-day hospitalization for a discogram.


7. Masala S, Anselmetti GC, Marcia S, et al. Treatment of painful Modic type I changes by vertebral augmentation with bioactive resorbable bone cement. Neuroradiology. 2014;56(8):637–45. doi:10.1007/s00234-014-1372-9.

The aim of this study was to evaluate the effectiveness of vertebral augmentation with calcium sulfate / hydroxyapatite resorbable cement in patients with low back pain resistant to conservative treatment with Modic type I changes. Over four years, 1124 patients were screened, and 218 underwent augmentation with resorbable cement. Patient’s symptoms were evaluated for intensity through an 11-point visual analog scale and for interference with daily life activities evaluated by Oswestry Disability Index. 79% of patients quickly improved during the first 4 weeks after treatment. 19% showed more gradual improvement over the first 6 months. The authors conclude that endplate augmentation by injection of low resorbable cement seems to be an effective therapeutic option for patients whose severe and resistant painful symptoms that can be attributed to Modic type I changes.

The theory is that the involved disc has “intersegmental instability”, and will have developed microfractures and inflammatory changes that the introduction of bone cement will stabilize.


8. Koivisto K, Kyllönen E, Haapea M, et al. Efficacy of zoledronic acid for chronic low back pain associated with Modic changes in magnetic resonance imaging. BMC Musculoskelet Disord. 2014;15:64. doi:10.1186/1471-2474-15-64.

The authors undertook a randomized, placebo-controlled, double-blinded trial to evaluate the efficacy of zoledronic acid for chronic LBP among patients with Modic change on MR. Inclusion criteria were 1) LBP lasting ≥3 months, with an intensity of ≥6 on a 10-cm VAS or an Oswestry Disability Index of ≥30%, and 2) Modic changes on MR. Patients were randomized into single intravenous infusion of zoledronic acid 5 mg (n = 20), or placebo (n = 20) groups. The mean difference between the groups in the primary outcome, intensity of LBP, was 1.4 in favor of zoledronic acid at one month. They observed no significant between-group difference in the intensity of LBP at one year. The authors considered the outcome encouraging regarding the use of zoledronic acid.

These results are somewhat tempered by the acute phase reactions (fever, flu-like symptoms, arthralgia) seen in 95% of the patients in the zoledronic acid group, compared to 35% in the placebo group.


9. Cecchetti S, Pereira B, Roche A, et al. Efficacy and safety of pamidronate in Modic type 1 changes: study protocol for a prospective randomized controlled clinical trial. Trials. 2014;15:117. doi:10.1186/1745-6215-15-117.

Pamidronate, with a mechanism of action on bone turnover, has shown some efficacy in open-label studies on inflammatory spondyloarthropathies that are resistant to NSAIDs. This efficacy has also has been demonstrated for various types of bone pain, such as Paget’s disease, fibrous dysplasia, and vertebral compression. The authors are recruiting for a double-blind, randomized, placebo- controlled, parallel group, phase two clinical trial. The endpoints will be measured at baseline, six weeks, three months and six months. The study product is disodium pamidronate 9 mg/ml, for slow intra- venous infusion. In the placebo group, the product used is a 500 ml bag of 0.9% sodium chloride solution. The primary outcome measure will be the difference in spinal pain assessed by VAS between the treatment group and the placebo group. Secondary outcome measures will include the French adaptation of the Roland-Morris Low Back Pain Questionnaire, Dallas and Fear Avoidance Beliefs Questionnaire, the McMaster Toronto Arthritis Patient Preference Disability Questionnaire and the Minimum Clinically Important Improvement/Patient Acceptable Symptom State questionnaire; measurements of finger-to-floor distance and the Schober test (used in rheumatology to measure the ability of a patient to flex his/her lower back); clinical signs of spinal inflammation, with assessment of the number of nighttime awakenings and the duration and severity of morning stiffness on a VAS.

Definitely worth reading the Background section. Interesting that Modic type I change is now considered “active discopathy”.

Annotated Bibliography, March 2015
Jeffrey Ross • Mayo Clinic, Phoenix

Dr. Jeffrey S. Ross is a Professor of Radiology at the Mayo Clinic College of Medicine, and practices neuroradiology at the Mayo Clinic in Phoenix, Arizona. His publications include over 100 peer-reviewed articles, nearly 60 non-refereed articles, 33 book chapters, and 10 books. He was an AJNR Senior Editor from 2006-2015, is a member of the editorial board for 3 other journals, and a manuscript reviewer for 10 journals. He became Editor-in-Chief of the AJNR in July 2015. He received the Gold Medal Award from the ASSR in 2013.