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Background Intervertebral disc therapies (IDT) for the management of non-specific chronic low back (NScLBP) pain are raising interest (1). Objectives To review evidence on the benefits and harms of IDT in people with NScLBP. Methods We searched 4 databases and conference abstracts, from inception to July 2018, for randomized trials of IDT versus placebo interventions, active comparators or usual care. Two independent investigators extracted data and assessed the risk of bias. The primary outcome was LBP intensity at short, intermediate and long terms (2). Secondary outcomes were LBP-specific activity limitation and safety (3). Our review was registered with the International Prospective Register of Systematic Reviews (CRD42019106336). Results Of 17 eligible trials, 5 trials (436 patients) assessed glucocorticoid (GC) IDT and were included in a quantitative synthesis. Twelve trials assessed IDT of other products including ozone (n=2, 140 patients), methylene blue (n=1, 72 patients), stems cells (n=1, 24 patients), glycerol (n=1, 11 patients), etanercept (n=2, 96 patients), tocilizumab (n=1, 60 patients), platelet-rich plasma (n=1, 47 patients), chymopapaine (n=1, 39 patients) and rhGDF-5 (n=2, 55 patients) and were included in a narrative synthesis. Standardized mean differences (SMD) of GC IDT for LBP intensity and activity limitations were -1.33 (-2.34;-0.32) and -0.76 (-1.85;0.34) at short-term, -2.22 (-5.34;0.90) and -1.60 (-3.51;0.32) at intermediate-term and -1.11 (-2.91;0.70) and -0.63 (-1.68;0.42) at long-term, respectively. OR of GC IDT for serious and minor adverse events were 1.13 (0.20; 4.59) and 0.97 (0.49;1.91). Conclusion GC IDT are associated with a reduction in LBP intensity at short-term in people with NScLBP. Positive effects are not sustained. There is no effect on activity limitations. References [1] Knezevic NN, Mandalia S, Raasch J, Knezevic I, Candido KD. Treatment of chronic low back pain - new approaches on the horizon. J Pain Res. 2017;10:1111-23. [2] Chiarotto A, Boers M, Deyo RA, Buchbinder R, Corbin TP, Costa LOP, et al. Core outcome measurement instruments for clinical trials in nonspecific low back pain. Pain. 2018;159(3):481-95. [3] Team QAaSM. Safety of medicines : a guide to detecting and reporting adverse drug reactions : why health professionals need to take action. In: Organization WH, ed. Geneva; 2002. Disclosure of Interests None declared

Importance Osteopathic manipulative treatment (OMT) is frequently offered to people with nonspecific low back pain (LBP) but never compared with sham OMT for reducing LBP-specific activity limitations. Objective To compare the efficacy of standard OMT vs sham OMT for reducing LBP-specific activity limitations at 3 months in persons with nonspecific subacute or chronic LBP. Design, setting, and participants This prospective, parallel-group, single-blind, single-center, sham-controlled randomized clinical trial recruited participants with nonspecific subacute or chronic LBP from a tertiary care center in France starting February 17, 2014, with follow-up completed on October 23, 2017. Participants were randomly allocated to interventions in a 1:1 ratio. Data were analyzed from March 22, 2018, to December 5, 2018. Interventions Six sessions (1 every 2 weeks) of standard OMT or sham OMT delivered by nonphysician, nonphysiotherapist osteopathic practitioners. Main outcomes and measures The primary end point was mean reduction in LBP-specific activity limitations at 3 months as measured by the self-administered Quebec Back Pain Disability Index (score range, 0-100). Secondary outcomes were mean reduction in LBP-specific activity limitations; mean changes in pain and health-related quality of life; number and duration of sick leaves, as well as number of LBP episodes at 12 months; and consumption of analgesics and nonsteroidal anti-inflammatory drugs at 3 and 12 months. Adverse events were self-reported at 3, 6, and 12 months. Results Overall, 200 participants were randomly allocated to standard OMT and 200 to sham OMT, with 197 analyzed in each group; the median (range) age at inclusion was 49.8 (40.7-55.8) years, 235 of 394 (59.6%) participants were women, and 359 of 393 (91.3%) were currently working. The mean (SD) duration of the current LBP episode was 7.5 (14.2) months. Overall, 164 (83.2%) patients in the standard OMT group and 159 (80.7%) patients in the sham OMT group had the primary outcome data available at 3 months. The mean (SD) Quebec Back Pain Disability Index scores for the standard OMT group were 31.5 (14.1) at baseline and 25.3 (15.3) at 3 months, and in the sham OMT group were 27.2 (14.8) at baseline and 26.1 (15.1) at 3 months. The mean reduction in LBP-specific activity limitations at 3 months was -4.7 (95% CI, -6.6 to -2.8) and -1.3 (95% CI, -3.3 to 0.6) for the standard OMT and sham OMT groups, respectively (mean difference, -3.4; 95% CI, -6.0 to -0.7; P = .01). At 12 months, the mean difference in mean reduction in LBP-specific activity limitations was -4.3 (95% CI, -7.6 to -1.0; P = .01), and at 3 and 12 months, the mean difference in mean reduction in pain was -1.0 (95% CI, -5.5 to 3.5; P = .66) and -2.0 (95% CI, -7.2 to 3.3; P = .47), respectively. There were no statistically significant differences in other secondary outcomes. Four and 8 serious adverse events were self-reported in the standard OMT and sham OMT groups, respectively, though none was considered related to OMT. Conclusions and relevance In this randomized clinical trial of patients with nonspecific subacute or chronic LBP, standard OMT had a small effect on LBP-specific activity limitations vs sham OMT. However, the clinical relevance of this effect is questionable. Trial registration ClinicalTrials.gov Identifier: NCT02034864.

Objectives: We aim to evaluate the benefits and harms of intervertebral disc therapies (IDTs) in people with non-specific chronic low back pain (NScLBP). Methods: We conducted a systematic review and meta-analysis of randomized trials of IDTs versus placebo interventions, active comparators or usual care. EMBASE, MEDLINE, CENTRAL and CINHAL databases and conference abstracts were searched from inception to June 2020. Two independent investigators extracted data. The primary outcome was LBP intensity at short term (1 week–3 months), intermediate term (3–6 months) and long term (after 6 months). Results: Of 18 eligible trials (among 1396 citations), five assessed glucocorticoids (GCs) IDTs and were included in a quantitative synthesis; 13 assessed other products including etanercept ( n = 2), tocilizumab ( n = 1), methylene blue ( n = 2), ozone ( n = 2), chymopapaine ( n = 1), glycerol ( n = 1), stem cells ( n = 1), platelet-rich plasma ( n = 1) and recombinant human growth and differentiation factor-5 ( n = 2), and were included in a narrative synthesis. Standardized mean differences (95% CI) for GC IDTs for LBP intensity and activity limitations were −1.33 (−2.34; −0.32) and −0.76 (−1.85; 0.34) at short term, −2.22 (−5.34; 0.90) and −1.60 (−3.51; 0.32) at intermediate term and −1.11 (−2.91; 0.70) and −0.63 (−1.68; 0.42) at long term, respectively. Odds ratios (95% CI) for serious and minor adverse events with GC IDTs were 1.09 (0.25; 4.65) and 0.97 (0.49; 1.91). Conclusion: GC IDTs are associated with a reduction in LBP intensity at short term in people with NScLBP. Positive effects are not sustained. IDTs have no effect on activity limitations. Our conclusions are limited by high heterogeneity and a limited methodological quality across studies. Registration PROSPERO: CRD42019106336.

Introduction/Background Active disc disease is characterized by inflammatory-like low back pain (LBP) and the presence of Modic 1 changes on MRI. Its prevalence ranges from 19% to 50% in patients with nonspecific chronic LBP. Pelvic parameters are important determinants of shear and compressive forces applied to the lumbar intervertebral disc. The association between an active disc disease and abnormal pelvic parameters has not been addressed yet. We aimed to compare pelvic parameters between chronic LBP patients with an active disc disease (Modic 1) and those without (Modic 0). Material and method We used a convenient sample from patients prospectively and consecutively recruited in a previous single center case-control pilot study. Cases were defined as chronic LBP male patients with an active disc disease on MRI and controls as patients without. Pelvic parameters, namely sacral slope, pelvic tilt and pelvic incidence, were assessed in an independent and standardized manner by two trained investigators using EOS system imaging performed at inclusion. Results Overall, 35 cLBP patients (13 cases and 22 controls) fulfilled inclusion criteria and had an EOS imaging available. Median age was 42 (35–51.5) years and median LBP duration 50 (33.5–104) months. Pelvic parameters did not differ between the 2 groups: absolute mean (95% IC) difference between Modic 0 and Modic 1 was −7.2° (−15.5; 1.0) for pelvic incidence, −3.7° (−8.7; 1.3) for pelvic tilt and −3.3 (−8.9; 2.3) for sacral slope. Conclusion Pelvic parameters in patients with chronic LBP and an active disc disease do not differ from those in patients without.

In the late 1980s, the description by Modic and colleagues of elementary discovertebral changes detected on MRI (Modic classification) suggested for the first time a possible correlation between anatomical and clinical features in a subgroup of patients with non-specific chronic low back pain. Degenerative disc disease is frequent and usually asymptomatic, but Modic 1 changes in the vertebral endplates adjacent to a degenerated disc are associated with inflammatory-like chronic low back pain and low-grade local and systemic inflammation, which led to the concept of ‘active discopathy’. Active discopathy shares some similarities with acute flares of peripheral osteoarthritis. Likewise, what triggers disc activation and how it self-limits remain unknown. A better understanding of mechanisms underlying disc activation and its self-limitation is of clinical relevance because it may enable the design of more targeted pharmacological and non-pharmacological interventions for the subgroup of patients with chronic low back pain and active discopathy. Here, we narratively review current disc-centred biomechanical and biochemical hypotheses of disc activation and discuss evidence of interactions with adverse personal and environmental factors.