ISSLS Prize in Bioengineering Science 2023: Age- and sex-related differences in lumbar intervertebral disc degeneration between patients with chronic low back pain and asymptomatic controls

Abstract

Purpose: Clinical management of disc degeneration in patients with chronic low back pain (cLBP) is hampered by the challenge of distinguishing pathologic changes relating to pain from physiologic changes related to aging. The goal of this study was to use imaging biomarkers of disc biochemical composition to distinguish degenerative changes associated with cLBP from normal aging.

Methods: T1ρ MRI data were acquired from 133 prospectively enrolled subjects for this observational study (80 cLBP, 53 controls; mean ± SD age = 43.9 ± 13.4 years; 61 females, 72 males). The mean T1ρ relaxation time in the nucleus pulposus (NP-T1ρ; n = 650 discs) was used as a quantitative biomarker of disc biochemical composition. Linear regression was used to assess associations between NP-T1ρ and age, sex, spinal level, and study group, and their interactions.

Results: NP-T1ρ values were lower in cLBP patients than controls (70.8 ± 22.8 vs. 76.4 ± 22.2 ms, p = 0.009). Group differences were largest at L5-S1 (ΔT1ρ_cLBP-control = -11.3 ms, p < 0.0001), representing biochemical deterioration typically observed over a 9-12 year period (NP-T1ρ declined by 0.8-1.1 ms per year [95% CI]). Group differences were large in younger patients and diminished with age. Finally, the age-dependence of disc degeneration was stronger in controls than cLBP patients.

Conclusion: Aging effects on the biochemical composition of the L5-S1 disc may involve a relatively uniform set of factors from which many cLBP patients deviate. NP-T1ρ values at L5-S1 may be highly relevant to clinical phenotyping, particularly in younger individuals.

Keywords: Aging; Chronic low back pain; Disc degeneration; Lumbar spine; T1ρ (T1rho) magnetic resonance imaging (MRI).

Fig. 1

a Mid-sagittal T1ρ MRI image showing lumbar disc segmentations and relaxation time maps. b The mean ± SD T1ρ relaxation time was computed in the nucleus pulposus (NP) region of each disc

Fig. 2

Mean (black bar), median (gray bar), inter-quartile range (box) NP T1ρ distribution (ms) for the control and cLBP groups. In the age- and sex-adjusted model, the cLBP group had lower mean NP-T1ρ values than the control group (p = 0.009). Females had lower NP T1ρ values than males (p = 0.0001, age-adjusted comparison). The interaction between group and sex was not statistically significant (p = 0.15)

Fig. 3

Mean (95% CI) NP-T1ρ by level. n = 133 discs per level, except L1–L2, for which n = 118 discs

Fig. 4

NP-T1ρ as a function of age at each lumbar level (p < 0.0001 each except cLBP at L5–S1, for which p = 0.02). At L5–S1, there was a statistically significant interaction between age and group (p = 0.0008), indicating that the relationship between age and disc degeneration (regression slope) differed between groups. Also at L5–S1, the Pearson’s correlation coefficient for the cLBP group (r = 0.3, p = 0.02) suggested a weak relationship between age and NP-T1ρ

Fig. 5

Histogram probability density functions (PDF) for T1ρ relaxation times according to disc Pfirrmann grade for all NP voxels (n = 146,387 voxels from 650 discs). Data are mean ± SD (range) or number (percent of total)