Propionibacterium acnes infected intervertebral discs cause vertebral bone marrow lesions consistent with Modic changes

Abstract

Modic type I change (MC1) are vertebral bone marrow lesions adjacent to degenerated discs that are specific for discogenic low back pain. The etiopathogenesis is unknown, but occult discitis, in particular with Propionibacteria acnes (P. acnes), has been suggested as a possible etiology. If true, antibiotic therapy should be considered for patients with MC1. However, this hypothesis is controversial. While some studies report up to 40% infection rate in herniated discs, others fail to detect infected discs and attribute reports of positive cultures to contamination during sampling procedure. Irrespective of the clinical controversy, whether it is biologically plausible for P. acnes to cause MC1 has never been investigated. Therefore, the objective of this study was to test if P. acnes can proliferate within discs and cause reactive changes in the adjacent bone marrow. P. acnes was aseptically isolated from a symptomatic human L4/5 disc with MC1 and injected into rat tail discs. We demonstrate proliferation of P. acnes and up-regulation of IL-1 and IL-6 within three days of inoculation. At day-7, disc degeneration was apparent along with fibrotic endplate erosion. TNF-a immunoreactivity was enhanced within the effected endplates along with cellular infiltrates. The bone marrow appeared normal. At day-14, endplates and trabecular bone close to the disc were almost completely resorbed and fibrotic tissue extended into the bone marrow. T-cells and TNF-a immunoreactivity were identified at the disc/marrow junction. On MRI, bone marrow showed MC1-like changes. In conclusion, P. acnes proliferate within the disc, induce degeneration, and cause MC1-like changes in the adjacent bone marrow. ß

P. acnes-Driven Disease Pathology: Current Knowledge and Future Directions

“…There has been some clinical evidence that patients with herniated nuclear (nucleus pulposus) disk material infected with anaerobic pathogens in general, and P. acnes in particular, are more likely develop inflammation and edema of the adjacent vertebrae (Modic changes type I) and back pain (Albert et al, 2013; Urquhart et al, 2015). Clinical and animal-based follow-ups are now corroborating the initial findings showing that local P. acnes proliferation causes upregulation of inflammatory markers and disk degeneration consistent with Modic changes (Aghazadeh et al, 2016; Dudli et al, 2016). There is now even first clinical evidence to suggest that bacterial infection of the intervertebral disk with P. acnes and/or Staphylococcus epidermidis may actually precede all other issues as the root cause of disk herniation and associated pathological changes (Rajasekaran et al, 2017).…”

Propionibacterium acnes biofilm is present in intervertebral discs of patients undergoing microdiscectomy

“…A recently described animal model demonstrates the ability of P . acnes to induce disc degeneration [17, 18]. However, in microbiologic culture data, contamination is difficult to exclude entirely, as P .…”

Histological Identification ofPropionibacterium acnesin Nonpyogenic Degenerated Intervertebral Discs

“…For example, some clinical studies have demonstrated that antibiotic therapy targeting the bacteria significantly reduced the low back pain and Modic changes in patients [9, 10]. In addition, inoculation of P. acnes into normal intervertebral discs of rats or rabbits induced severe disc degeneration and Modic changes [11, 12]. For this reason, P. acnes is thought to be involved in a previously undiscovered pathogeny for series of disc diseases.…”