Eero Kyllönen

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 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 (IP-10) 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.

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. 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. 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. 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. The registration number in ClinicalTrials.gov is NCT01330238 and the date of registration February 11, 2011.

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).

Background: A chronic pain condition may result in altered autonomic nervous system regulation in various patient populations. We evaluated whether autonomic regulation differs between sciatica patients referred to spine surgery and age-matched healthy controls analyzed with heart rate variability techniques (HRV).Methods: HRV of patients (n = 201) and healthy controls (n = 138) were measured in standing conditions (5 min). High frequency (HF) power as an index of cardiac vagal modulation and the low-to-high-frequency (LF/HF) ratio and short-term fractal scaling exponent α₁as indices of sympathovagal balance were analyzed. Pain intensity was assessed on a Visual Analog Scale (VAS) and perceived disability with Oswestry Disability Index.Results: The Oswestry and VAS scores were higher in the patients than in the controls (p < 0.0001 for both). HF power was markedly lower for the patients compared to the controls (p < 0.0001). The LF/HF ratio and α₁were higher in the patients than in the controls (p < 0.01 for both). After adjusting for sex, smoking, BMI, and leisure-time physical activity, HF power (p = 0.011) and α₁(p = 0.012) still differed between the groups. Among the patients, HF power was slightly associated with the duration of chronic pain (r = −.232, p = 0.003).Conclusions: Sciatica patients referred to spine surgery had altered cardiac autonomic regulation expressed as decreased vagal activity and an increased sympathovagal balance toward sympathetic dominance when compared with age-matched healthy controls.

A 2-year randomized controlled trial. To examine the possible preventive or aggravating effect of estrogen-progestin treatment on the back symptoms of slim premenopausal women with low lumbar spine bone mineral density. The incidence of back pain, sciatica, or both starts to increase clearly among 45-54-year-old Finnish women. Forty-eight 39- to 49-year-old premenopausal women with a body mass index of 21 or less and a lumbar spine bone mineral density (L2-L4) of 1.1 +/- 1 g/cm3 or less compared with the normative population were recruited into the study. The women were assigned randomly to receive either estradiol-noretisteron acetate treatment or placebo. Back pain, symptoms, and disability were assessed with the Million and Oswestry questionnaires and pain drawings during the follow-up period at 0, 12, and 24 months. Inquiry also was made concerning previous back pain and sciatica history. There was a statistically significant decrease in nighttime back pain (P < 0.001) and the total Oswestry disability scores (P < 0.004) in the hormone-treated group compared with the control group during the follow-up, but no statistically significant differences were found in daytime back pain. At baseline, the cumulative incidence in a history of pain radiating from the buttock to the foot in this osteopenic study group was 31/48, (64.5%; 95% CI 50.5-78.6), which is much more than the predicted 20/48, (42.4%; 95% CI 39.0-45.7) at this age according to a previous population study. The cumulative incidence of at least one back pain episode 44/48, (91.7%; 95% CI 83.6-99.8) was somewhat higher in these participants than was predicted for a comparative population of women this age, 38/48 (79.2%; 95% CI 70.2-87.3). It seems that this regimen may have alleviating effects on nighttime back pain and functional back disability in slim osteopenic premenopausal women.

The purpose of this study was to examine the influence of estrogen-progestin replacement therapy and exercise on the lumbar spine mobility and back symptoms of early postmenopausal women. The population sample consisted of 78 healthy, 49- to 55-year-old women, 0.5–5 years after menopause, who were randomized into three groups, two receiving different protocols of estradiol valerate combined with medroxyprogesterone acetate replacement therapy, and the third group a placebo. These groups were then randomized into exercise and control cases and monitored for 2 years. The mobility of the lumbar spine was measured and symptoms investigated using the Million and Oswestry pain and disability questionnaires and pain drawings at the baseline and after 1 and 2 years. During the follow-up, the mobility of the lumbar spine decreased in all six groups. The decrease was most evident in those who had been the most flexible at baseline (P < 0.0001). The decrease was less notable in the hormone replacement therapy groups than in the control group. When the replacement therapy groups were pooled together, the difference was significant at a P < 0.05 level. No difference was seen between the hormone combinations. The exercise intervention was insufficient to influence lumbar spine mobility. Only sporadic cases of back symptoms appeared and disappeared among the subjects during the follow-up, and no preventive or aggravating effects of hormone replacement therapy or the exercise program on symptoms were detected.