Serum biomarkers for Modic changes in patients with chronic low back pain.

PURPOSE: Lumbar Modic change (MC) can serve as a diagnostic marker as well as an independent source of chronic low back pain (CLBP). This study aimed to test for the existence of serum biomarkers in CLBP patients with MC. METHODS: Age- and sex-matched CLBP patients with confirmed MC on lumbar MRI (n = 40) and pain-free controls (n = 40) were assessed. MC was classified into M1, predominating M1, predominating M2 and M2. MC volumes were calculated. Fasting blood samples were assessed for inflammatory mediators, signalling molecules, growth factors and bone turnover markers. Serum concentrations of 46 biomarkers were measured. RESULTS: Median concentrations of interleukin (IL)-15 (p < 0.001), IL-8 (p < 0.001), tumour necrosis factor (TNF)-alpha (p < 0.001), Eotaxin-1 (p < 0.05), Eotaxin-3 (p < 0.001), monocyte chemotactic protein (MCP)-1 (p < 0.05), macrophage inflammatory protein (MIP)-1alpha (p < 0.01), TEK receptor tyrosine kinase (Tie)-2 (p < 0.001), vascular cell adhesion molecule (VCAM)-1 (p < 0.001), RANTES (p < 0.001), C telopeptide of type I collagen (CTX)-1 (p < 0.001), vascular endothelial growth factor (VEGF)-C (p < 0.001), VEGF-D (p < 0.05), fms-related tyrosine kinase (Flt)-1 (p < 0.01) and intercellular adhesion molecule (ICAM)-1 (p < 0.01) were significantly higher among controls. IL-1sRII (23.2 vs. 15.5 ng/ml, p < 0.001) and hepatocyte growth factor (HGF)-1 (169 vs. 105 pg/ml, p < 0.01) concentrations were significantly higher among patients. Type or volume of MC was not associated with biomarker concentrations. CONCLUSIONS: This is the first study to assess the blood serum biomarker profile in individuals with CLBP with MC. Several biomarkers were suppressed, while two markers (IL-1sRII and HGF) were elevated among MC patients, irrespective of MC type or size, with CLBP compared with asymptomatic controls.

The effect of zoledronic acid on type and volume of Modic changes among patients with low back pain.

BACKGROUND: Modic changes (MC) are associated with low back pain (LBP). In this study, we compared changes in size and type of MC, after a single intravenous infusion of 5 mg zoledronic acid (ZA) or placebo, among chronic LBP patients with MC on magnetic resonance imaging (MRI), and evaluated whether the MRI changes correlate with symptoms. METHODS: All patients (N = 19 in ZA, 20 in placebo) had MRI at baseline (0.23-1.5 T) and at one year (1.5-3 T). We evaluated the level, type and volume of all the MC. The MC were classified into M1 (M1 (100%)), predominating M1 (M1/2 (65:35%)) or predominating M2 (M1/2 (35:65%)), and M2 (M2 (100%)). The first two were considered M1-dominant, and the latter two M2-dominant. Volumes of M1 and M2 were calculated separately for the primary MC, which was assumed to cause the symptoms, and the other MC. We analysed the one-year treatment differences in M1 and M2 volumes using analysis of covariance with adjustments for age, sex, body mass index, and smoking. The correlations between the MRI changes and the changes in LBP symptoms were analysed using Pearson correlations. RESULTS: In the ZA group, 84.2% of patients had M1-dominant primary MC at baseline, compared to 50% in the placebo group (p = 0.041). The primary MC in the ZA group converted more likely to M2-dominant (42.1% ZA, 15% placebo; p = 0.0119). The other MC (15 ZA, 8 placebo) were on average 42% smaller and remained largely M2-dominant. The M1 volume of the primary MC decreased in the ZA group, but increased in the placebo group (-0.83 cm3 vs 0.91 cm3; p = 0.21). The adjusted treatment difference for M1 volume was -1.9 cm3 (95% CI -5.0 to 1.2; p = 0.22) and for M2 volume 0.23 cm3 (p = 0.86). In the MC that remained M1-dominant, volume change correlated positively with increased symptoms in the placebo group, whereas the correlations were negative and weak in the ZA group. CONCLUSIONS: Zoledronic acid tended to speed up the conversion of M1-dominant into M2-dominant MC and decrease the volume of M1-dominant MC, although statistical significance was not demonstrated. TRIAL REGISTRATION: The registration number in ClinicalTrials.gov is NCT01330238 and the date of registration February 11, 2011.

Efficacy of zoledronic acid for chronic low back pain associated with Modic changes in magnetic resonance imaging.

BACKGROUND: Modic changes (MC) are associated with low back pain (LBP), but effective treatments are lacking. The aim of this randomized, placebo-controlled, double-blinded trial was to evaluate the efficacy of zoledronic acid (ZA) for chronic LBP among patients with MC in magnetic resonance imaging (MRI). METHODS: Inclusion criteria were LBP lasting ≥3 months, with an intensity of ≥6 on a 10-cm VAS or an Oswestry Disability Index (ODI) of ≥30%, and MC in MRI. Patients were randomized into single intravenous infusion of ZA 5 mg (n = 20), or placebo (n = 20) groups. The primary outcome was LBP intensity, secondary outcomes leg pain intensity, ODI, health-related quality of life (RAND-36), lumbar flexibility, sick leaves and use of pain medication. The treatment differences at one month and one year were analysed using ANCOVA with adjustment for the baseline score. RESULTS: The mean difference (MD) between the groups in the primary outcome, intensity of LBP, was 1.4 (95% confidence intervals (CI) 0.01 to 2.9) in favour of ZA at one month. We observed no significant between-group difference in the intensity of LBP at one year (MD 0.7; 95% CI -1.0 to 2.4) or in secondary outcomes at any time point except that 20% of patients in the ZA group used non-steroidal anti-inflammatory drugs at one year compared to 60% in the placebo group (P = 0.022). Acute phase reactions (fever, flu-like symptoms, arthralgia) emerged in 95% of the patients in the ZA group, compared to 35% in the placebo group. CONCLUSIONS: ZA was effective in reducing the intensity of LBP in the short term and in reducing the use of NSAIDs within the time span of one year among patients with chronic LBP and MC confirmed in MRI. Although the results seem encouraging, larger studies are required to analyse the effectiveness and safety of ZA for patients with MC. TRIAL REGISTRATION: ClinicalTrial.gov identifier NCT01330238.

The Effect of Zoledronic Acid on Serum Biomarkers among Patients with Chronic Low Back Pain and Modic Changes in Lumbar Magnetic Resonance Imaging.

The aim of the current study was to compare changes in serum biomarkers, including inflammatory mediators, signaling molecules, growth factors and markers of bone turnover after a single intravenous infusion of 5 mg zoledronic acid (ZA, a long-acting bisphosphonate; n = 20) or placebo (n = 20) among patients with Modic changes (MC) and chronic low back pain in a randomized controlled design. The MCs were classified into M1, predominating M1, predominating M2, and M2. We measured the serum concentrations of 39 biomarkers at baseline, and one month and one year after treatment. After Benjamini-Hochberg (B-H) correction, we observed significant differences in three biomarkers over one year: Interferon-γ-inducible protein (IP10) had risen in the ZA group (p = 0.005), whereas alkaline phosphatase (AFOS) and intact procollagen I N-terminal propeptide (iPINP) had significantly decreased in the ZA group, but had not changed in the placebo group (p < 0.001 for both). Change in iPINP correlated with change in the volume of all MC and M1 lesions. ZA downregulated bone turnover markers as expected and, surprisingly, increased the chemokine IP-10 relative to placebo treatment. This adds to our knowledge of the effects of ZA on MC and the biomarkers that signal this process.

Individual or group rehabilitaion for people with low back pain: a comparative study with 6-month follow-up.

OBJECTIVE: To compare the effectiveness of group rehabilitation and individually dosed rehabilitation in treating chronic low back pain. DESIGN: Institutional rehabilitation intervention in 2 nonrandomized groups with a 6-month post-intervention follow-up. SUBJECTS: Persons with chronic low back pain: 64 group-rehabilitated and 66 individually rehabilitated. METHODS: The rehabilitation period for all subjects was 21 days. Those being group-rehabilitated, about 10 patients per group, had a common programme including 3-5 exercise groups per day, group discussions and lectures including back and neck school. Local physical therapy was given if neeeded. The individually rehabilitated subjects had individually designed programmes: local physical therapy, muscle strengthening programme, group exercises and participating in back school. The duration of the guided programme was 62 hours for group rehabilitation and 45 hours for individual rehabilitation. RESULTS: During the rehabilitation period the strength and flexibility of individually rehabilitated subjects improved more than that of group-rehabilitated subjects (p < 0.05 and p < 0.01, respectively). After the 6-month follow-up period, group-rehabilitated subjects showed a decrease in the Oswestry and pain indexes, while individually rehabilitated subjects showed an increase in the Oswestry index. The group-rehabilitated subjects evaluated the goals of rehabilitation to have been attained better and considered themselves better motivated in self-care. The costs of the 2 rehabilitation programs were approximately equal. CONCLUSION: These tentative results suggest that group rehabilitation can compete with individual rehabilitation at least in short-term follow-up.