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. 2023 Jun;31(6):809-818.
doi: 10.1016/j.joca.2023.02.005. Epub 2023 Feb 18.

Biomarkers and longitudinal changes in lumbar spine degeneration and low back pain: the Johnston County Osteoarthritis Project

A P Goode  1 , R J Cleveland  2 , V B Kraus  3 , K A Taylor  4 , S Z George  5 , T A Schwartz  6 , J Renner  7 , J L Huebner  8 , J M Jordan  9 , Y M Golightly  10
Affiliations

Biomarkers and longitudinal changes in lumbar spine degeneration and low back pain: the Johnston County Osteoarthritis Project

A P Goode et al. Osteoarthritis Cartilage. 2023 Jun.

Abstract

Objective: To determine if baseline biomarkers are associated with longitudinal changes in the worsening of disc space narrowing (DSN), vertebral osteophytes (OST), and low back pain (LBP).

Design: Paired baseline (2003-2004) and follow-up (2006-2010) lumbar spine radiographs from the Johnston County Osteoarthritis Project were graded for severity of DSN and OST. LBP severity was self-reported. Concentrations of analytes (cytokines, proteoglycans, and neuropeptides) were quantified by immunoassay. Pressure-pain threshold (PPT), a marker of sensitivity to pressure pain, was measured with a standard dolorimeter. Binary logistic regression models were used to estimate odd ratios (OR) and 95% confidence intervals (CI) of biomarker levels with DSN, OST, or LBP. Interactions were tested between biomarker levels and the number of affected lumbar spine levels or LBP.

Results: We included participants (n = 723) with biospecimens, PPT, and paired lumbar spine radiographic data. Baseline Lumican, a proteoglycan reflective of extracellular matrix changes, was associated with longitudinal changes in DSN worsening (OR = 3.19 [95% CI 1.22, 8.01]). Baseline brain-derived neuropathic factor, a neuropeptide, (OR = 1.80 [95% CI 1.03, 3.16]) was associated with longitudinal changes in OST worsening, which may reflect osteoclast genesis. Baseline hyaluronic acid (OR = 1.31 [95% CI 1.01, 1.71]), indicative of systemic inflammation, and PPT (OR = 1.56 [95% CI 1.02, 2.31]) were associated with longitudinal increases in LBP severity.

Conclusion: These findings suggest that baseline biomarkers are associated with longitudinal changes occurring in structures of the lumbar spine (DSN vs OST). Markers of inflammation and perceived pressure pain sensitivity were associated with longitudinal worsening of LBP.

Keywords: Biomarkers; Cohort study; Intervertebral disc degeneration; Low back pain; Spine degeneration.

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Conflict of interest statement

Conflict of interest: All authors disclose they have no financial or personal relationships with other people or organizations that could potentially and inappropriately bias their work and conclusions.

Figures

Figure 1.
Figure 1.
Flow of study participants from time point 2 (T2) to time point 3 (T3). JoCoOA= Johnston County Osteoarthritis Project; DSN= disc space narrowing; LBP= lower back pain. *Covariates: age, race, sex, BMI, knee OA, having 2+ comorbidities (CVD, hypertension, diabetes, liver disease, cancer, depression), NSAIDs.
Figure 2.
Figure 2.. Baseline Biomarker Associations with Longitudinal Changes in Worsening of Disc Space Narrowing
Associations between logarithmically-transformed biomarkers and change in disc space narrowing (DSN) score from T2 to T3. Outcome is worsening change in disc space narrowing (n=334) vs no change (n=372). Adjusted for the following measures at baseline (T2): Model 1: DSN Score, age, race, sex Model 2: DSN Score, age, race, sex, body mass index (BMI), knee osteoarthritis (OA), having 2+ comorbidities, non-steroidal anti-inflammatory drugs (NSAIDs) Model 3: OST Score Change in the same model; baseline values of DSN Score, OST Score, age, race, sex, BMI, knee OA, having 2+ comorbidities, NSAIDs. OR = Odds Ratio, CI = Confidence Interval, BDNF=brain derived neurotrophic factor; CTX-II=collagen telopeptide-II; CXCL6= C-X-C Motif Chemokine Ligand 6; DSN=disc space narrowing; HA= hyaluronan; IL-6=interleukin-6; NPY=neuropeptide-Y; OPG=osteoprotegerin; RANTES=Regulated upon Activation, Normal T Cell Expressed and Presumably Secreted.
Figure 3.
Figure 3.. Baseline Biomarker Associations with Longitudinal Changes in Worsening of Osteophytes
Associations between logarithmically-transformed biomarkers and change in osteophyte (OST) score from T2 to T3. Outcome is change in osteophyte score ≥2 (n=424) vs change <2 (n=282). Adjusted for the following measures at baseline (T2): Model 1: OST Score, age, race, sex Model 2: OST Score, age, race, sex, body mass index (BMI), knee osteoarthritis (OA), having 2+ comorbidities, non-steroidal anti-inflammatory drugs (NSAIDs) Model 3: OST and DSN Score Change in the same model; baseline values of DSN Score, age, race, sex, BMI, knee OA, having 2+ comorbidities, NSAIDs. OR = Odds Ratio, CI = Confidence Interval, BDNF=brain derived neurotrophic factor; CTX-II=collagen telopeptide-II; CXCL6= C-X-C Motif Chemokine Ligand 6; DSN=disc space narrowing; HA= hyaluronan; IL-6=interleukin-6; NPY=neuropeptide-Y; OPG=osteoprotegerin; RANTES=Regulated upon Activation, Normal T Cell Expressed and Presumably Secreted.
Figure 4.
Figure 4.. Baseline Biomarker Associations with Longitudinal Changes in Worsening of Low Back Pain
Associations between logarithmically-transformed biomarkers and change in low back pain severity from T2 to T3. Outcome is increase in pain severity (n=206) vs no change (n=377). Excludes n=46 with maximum pain severity at baseline and n=62 with pain improvement. Adjusted for the following measures at baseline (T2): Model 1: Pain severity, age, race, sex Model 2: Pain severity, age, race, sex, body mass index, knee osteoarthritis, having 2+ comorbidities, non-steroidal anti-inflammatory drugs. OR = Odds Ratio, CI = Confidence Interval, BDNF=brain derived neurotrophic factor; CTX-II=collagen telopeptide-II; CXCL6= C-X-C Motif Chemokine Ligand 6; DSN=disc space narrowing; HA= hyaluronan; IL-6=interleukin-6; NPY=neuropeptide-Y; OPG=osteoprotegerin; RANTES=Regulated upon Activation, Normal T Cell Expressed and Presumably Secreted
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References

    1. Muraki S, Akune T, Oka H, Ishimoto Y, Nagata K, Yoshida M, et al. Incidence and risk factors for radiographic lumbar spondylosis and lower back pain in Japanese men and women: the ROAD study. Osteoarthritis Cartilage 2012; 20: 712–718. - PubMed
    1. Muraki S, Oka H, Akune T, Mabuchi A, En-Yo Y, Yoshida M, et al. Prevalence of radiographic lumbar spondylosis and its association with low back pain in elderly subjects of population-based cohorts: the ROAD study. Ann Rheum Dis 2009; 68: 1401–1406. - PubMed
    1. Goode AP, Cleveland RJ, George SZ, Kraus VB, Schwartz TA, Gracely RH, et al. Different phenotypes of osteoarthritis in the lumbar spine reflected by demographic and clinical characteristics: The Johnston County Osteoarthritis Project. Arthritis Care Res (Hoboken) 2020; 72: 974–981. - PMC - PubMed
    1. Goode AP, Cleveland RJ, George SZ, Schwartz TA, Kraus VB, Renner JB, et al. Predictors of lumbar spine degeneration and low back pain in the community: The Johnston County Osteoarthritis Project. Arthritis Care Res (Hoboken) published online ahead of print, 2021. doi:10.1002/acr.24643. - DOI - PMC - PubMed
    1. Goode AP, Marshall SW, Renner JB, Carey TS, Kraus VB, Irwin DE, et al. Lumbar spine radiographic features and demographic, clinical, and radiographic knee, hip, and hand osteoarthritis. Arthritis Care Res (Hoboken) 2012; 64: 1536–1544. - PMC - PubMed

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