Comorbidities associated with cervical spine degenerative disc disease

Mark J. Lambrechts; Kyle Maryan; Wyatt Whitman; Tzu-Chuan Yen; Jinpu Li; Emily V. Leary; James L. Cook; Theodore J. Choma

doi:10.1016/j.jor.2021.07.008

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26 (); 98-102

doi:

10.1016/j.jor.2021.07.008

Comorbidities associated with cervical spine degenerative disc disease

Mark J. Lambrechts^a,, Kyle Maryan^b, Wyatt Whitman^b, Tzu-Chuan Yen^a, Jinpu Li^a, Emily V. Leary^a,c, James L. Cook^a,c, Theodore J. Choma^a,c

a Department of Orthopaedic Surgery, University of Missouri, Columbia, MO, USA

b University of Missouri School of Medicine, Columbia, MO, USA

c Thompson Laboratory for Regenerative Orthopaedics, University of Missouri, Columbia, MO, USA

∗Corresponding author: Mark J. Lambrechts. mark.lambrechts2016@gmail.com

Received: 2021-5-17, Accepted: 2021-7-11, Published: 2021-7-16

Professor P K Surendran Memorial Education Foundation

Disclaimer:
This article was originally published by Reed Elsevier India Pvt. Ltd. and was migrated to Scientific Scholar after the change of Publisher.

Abstract

Determining important links between medical comorbidities and cervical spine degenerative disc disease (DDD) will help elucidate pathomechanisms of disc degeneration. Electronic medical records and magnetic resonance imaging were retrospectively reviewed to evaluate 799 patients assessed for cervical spine pathology. Bivariate analysis identified older age, diabetes, ASA class, cancer, COPD, depression, hypertension, hypothyroidism, Medicare status, peripheral vascular disease, history of previous cervical spine surgery, smoking, and lower median household income as having strong associations with increased cumulative grade of cervical spine DDD. This study provides evidence suggesting aging and accumulation of medical comorbidities influence severity of cervical spine DDD.

Keywords

Cervical spine

Degenerative disc disease

Pathomechanisms

Electronic medical records

Magnetic resonance imaging

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1 Introduction

Cervical spine degenerative disc disease (DDD) has been implicated as a potential source of pain and neurologic compromise with increasing prevalence in older age. Matsumoto et al. reported that based on cervical spine MRI, more than 80% of patients over the age of 60 years had evidence for disc degeneration, while less than 20% of patients under the age of 20 years showed evidence for disc degeneration.¹ However, the relationship between aging and cervical spine DDD may be influenced by comorbidities as the number of medical comorbidities increase with older age.² Importantly, specific medical comorbidities including hypothyroidism, smoking, cardiovascular disease, and diabetes have been linked to higher incidence of lumbar spine DDD.^3–9 However, these associations have not been established for cervical spine DDD.

Diabetes mellitus is a medical comorbidity that is often evaluated due to its profound effects on musculoskeletal disorders, and there is contrasting evidence regarding diabetes’ association with disc degeneration. Although a four-year longitudinal study reported diabetes to be associated with upper lumbar DDD,¹⁰ another study assessing twins reported that diabetes was not associated with lumbar spine disc degeneration when accounting for age and BMI.¹¹ Based on the increasing prevalence of diabetes in the United States, now estimated at 9.4% of Americans,¹² determining the effects of controlled and uncontrolled diabetes on grade and severity of cervical spine DDD in conjunction with aging and other relevant comorbidities is critical to evidence-based education and treatment of patients with cervical spine DDD. Importantly, the variance in anatomy (uncovertebral joints in the cervical spine) and biomechanics (cervical spine intervertebral discs are better able to withstand compression forces, but are less tolerant to bending forces) suggests that aging, diabetes, and other medical comorbidities may have different effects for cervical spine DDD versus lumbar spine DDD such that they should be investigated independently.^13–15

The socioeconomic burden caused by low back and neck pain are staggering. Combined, cervical and lumbar spine disorders consistently rank among the largest United States healthcare expenditures, exceeding 85 billion dollars annually.¹⁶ As an example, a middle-aged patient undergoing uncomplicated anterior cervical discectomy and fusion (ACDF) encumbers an average of $31,178 in long-term medical costs alone.¹⁷ These costs exponentially increase when comorbidities must be managed and/or complications are encountered. As such, characterizing the influences of patient-related factors on cervical spine DDD could significantly mitigate healthcare costs in addition to determining targets for preventative and therapeutic strategies for this common musculoskeletal disease.

Therefore, the primary objective of this study was to determine if age and/or relevant medical comorbidities influenced grade and severity of symptomatic cervical spine DDD. Secondary objectives of the study were to assess the cumulative grade and severity of symptomatic cervical spine DDD in association with: 1) level of glycemic control (blood glucose >200, HgA1c > 8.0%, insulin use), and 2) socioeconomic measures including race and median household incomes. The study was designed to test the hypothesis that older age and multiple medical comorbidities would have strong associations with increased severity and cumulative grade of cervical disc degeneration.

2 Methods

With institutional review board approval, electronic medical records (EMRs) were searched to identify patients who underwent 1.5 T cervical spine MRI (CPTs 72141 and 72156) at the University of Missouri during the years 2011–2019 inclusive. If multiple MRIs were performed for the same patient, only the first-performed MRI was reviewed. Patients were then subdivided based on documented diagnosis of diabetes mellitus (Fig. 1). Cervical spine MRIs were reviewed by a single author (TCY) who was blinded to all other patient-related data. Each intervertebral disc between segments C2-3 to C7-T1 was assigned a numerical grade (0–3) using the Suzuki classification (Fig. 2). The Suzuki classification grades cervical spine MRIs based on a combination of disc desiccation and disc height loss. A grade of 0 indicates no desiccation or height loss and the score increases in severity to grade 3, defined as complete desiccation and near complete height loss. Using the Suzuki classification grades, we were then able to calculate the severity of cervical disc degeneration (highest graded intervertebral disc in the cervical spine) and cumulative grade of cervical spine DDD (combined grade of each intervertebral disc summed together). Disc spaces within a fusion construct were not graded.

Flow chart illustrating how patients were identified and subdivided based on documented diagnosis of diabetes mellitus.

Suzuki classification for grading cervical spine degenerative disc disease.

Health data were extracted from the EMR. Demographic characteristics and comorbidities were tabulated (Table 1). Diabetes control was determined based on highest A1c level, highest reported blood glucose, and insulin use (yes/no) recorded in the EMR for the 3 years prior to MRI. Insurance status (self-pay, private insurance, veteran's insurance, Medicare insurance, Workers compensation, and Medicaid insurance) was recorded and patients' zip codes were used to determine median household incomes.

Table 1 Demographic information for cohort. Values are means (std) or frequency.

	OverallN = 799	DiabeticN = 310	Non-diabeticN = 489	p-value
Age	52.7 (13.9)	54.7 (13.1)	51.4 (14.2)	<0.001
Male (%)	367 (46)	143 (46)	224 (46)	1.00
BMI	32.0 (7.7)	34.5 (7.9)	30.3 (7.1)	<0.001
White (%)	705 (88)	269 (87)	436 (89)	0.38
Number of cervical spine levels fused	6	3	3	1.00

2.1

2.1 Statistical analyses

Based on the Shapiro–Wilk test for normality, independent sample student t-tests, simple linear regression, or Mann-Whitney tests for non-parametric data were used to assess associations between diabetes status and Suzuki classification for each cervical segment, most affected disc, and total disc degeneration in the cervical spine. Chi-square or Fisher's Exact tests were further used to determine associations between medical comorbidities and Suzuki grades for each cervical intervertebral disc. One-sided p-values were considered and all tests were adjusted for multiple comparisons using the Benjamini-Hochberg method. Multivariate linear models considered Suzuki grading scores as continuous outcomes for each segment and also considered insurance status, age, ASA grade and diabetes status.

3 Results

Electronic medical records identified 803 patients meeting initial inclusion criteria. Four cervical spine MRIs were inaccessible, resulting in a final cohort of 799 patients (310 diabetics and 489 non-diabetics for analyses (Fig. 1)). Demographics for this patient population are provided in (Table 1). Both groups were primarily identified as white race. Those with diabetes were significantly (p < 0.001) older (mean age of 54.7 ± 13.1 years) compared to those without diabetes (mean age of 51.4 ± 14.2 years). Similarly, BMI was significantly (p < 0.001) higher for those with diabetes (mean of 34.5 ± 7.9) compared to those without diabetes (mean of 30.3 ± 7.1). Importantly, there was no significant difference (P = 1.00) in number of surgically fused discs between diabetic and non-diabetic cohorts. One patient in the non-diabetic cohort had a three-level fusion and three patients in the diabetic cohort each had a single level fusion.

Both grade and severity of cervical spine disc degeneration as measured by MRI Suzuki grading were significantly higher in diabetics compared to those without diabetes (Table 2). The following comorbidities were also significantly associated with increased cumulative grade of disc degeneration in the cervical spine: older age, diabetes, higher ASA classification, cancer, COPD, depression, hypertension, hypothyroidism, Medicare insurance status, peripheral vascular disease, number of previous cervical spine surgeries, smoking, and decreased median household income (Table 3). Each of these except for COPD, increasing ASA classification, previous cervical spine surgeries, and decreased median household income was also significantly associated with increased severity of cervical spine disc degeneration. Only non-white race demonstrated an increased severity of disc degeneration without an increased cumulative grade of disc degeneration.

Table 2 Differences in diabetic vs. non-diabetic degenerative disc disease scores, based on Mann-Whitney tests.

Suzuki Grading Scale	Diabetic			Non-diabetic			p-value
Suzuki Grading Scale	Mean	Median	Std Dev	Mean	Median	Std Dev	p-value
C2 -3 Grading	1.91	2	0.39	1.83	2	0.49	0.009
C3 -4 Grading	2.06	2	0.57	1.91	2	0.66	<0.0001
C4 -5 Grading	2.16	2	0.71	2.01	2	0.85	0.002
C5 -6 Grading	2.61	3	0.75	2.43	3	0.95	0.007
C6 -7 Grading	2.41	3	0.85	2.09	2	1.05	<0.0001
C7 -T1 Grading	1.64	2	0.74	1.34	1	0.84	<0.0001
Combined Score	12.8	13	2.61	11.61	12	3.62	<0.0001
Highest Grade	2.88	3	0.6	2.74	3	0.76	0.005

Table 3 Univariate analysis of comorbidities demonstrating differences in disc degeneration patient demographics or comorbidities. Both highest graded intervertebral disc and combined grade of all cervical spine discs are shown. Grade of 1 for adjusted P value significance indicates an association between the medical comorbidity and degenerative disc disease.

Comorbidities	Suzuki Grading	Test Used	P-value	Adjusted P value Significance
Age	Highest	Linear model	<0.0001	1
Age	Combined	Linear model	<0.0001	1
ASA class	Highest	Fisher-exact test	0.2152	0
ASA class	Combined	Fisher-exact test	0.0022	1
Cancer	Highest	Chi-squared test	0.0029	1
Cancer	Combined	Fisher-exact test	0.0125	1
COPD	Highest	Chi-squared test	0.0755	0
COPD	Combined	Fisher-exact test	0.0163	1
Depression	Highest	Chi-squared test	0.0169	1
Depression	Combined	Fisher-exact test	0.0042	1
Hypertension	Highest	Chi-squared test	0	1
Hypertension	Combined	Fisher-exact test	0.0022	1
Hypothyroidism	Highest	Chi-squared test	0.0349	1
Hypothyroidism	Combined	Fisher-exact test	0.0243	1
Insurance type	Highest	Fisher-exact test	0.0022	1
Insurance type	Combined	Fisher-exact test	0.0022	1
Peripheral vascular disease	Highest	Chi-squared test	0.0238	1
Peripheral vascular disease	Combined	Fisher-exact test	0.0022	1
Smoking status	Highest	Chi-squared test	0.0126	1
Smoking status	Combined	Fisher-exact test	0.0071	1

All comorbidities were further grouped into predominant location of disc degeneration. Older age, higher ASA, cancer, depression, hypertension, and Medicare insurance type were all associated with significantly greater grade of DDD at nearly every intervertebral disc in the cervical spine based on Suzuki grades. Hypothyroidism (C2-3, C5-6, and C7-T1) and OSA (C3-4, C6-7, and C7-T1) predominantly affected intervertebral disc degeneration near the cervicothoracic junction, while asthma (C4-5), and chronic pain (C2-3) tended to affect cervical DDD in the upper cervical spine (Supplementary Appendix A). COPD (C3-4 and C5-T1), peripheral vascular disease (C2-3 and C4–C7) and smoking (C3-4, C5-6, and C6-7) appeared to have no predilection for increased grade of DDD based on cephalad or caudal levels of the cervical spine (Supplementary Appendix B). Insulin use, blood glucose levels >200, and HgA1c levels >8.0% were not associated with increased grade or severity of DDD in diabetics (p > 0.05) (Table 4). Multiple other comorbidities were also associated with increased Suzuki grade for cervical DDD at a single disc segment, but this did not reach significance for an increased cumulative grade of cervical spine DDD.

Table 4 Diabetic control.

Suzuki Grades	P-values
Suzuki Grades	Taking insulin	Elevated Blood Glucose	High HgA1c
C2-3 Grading	0.5149	0.9305	0.9968
C3-4 Grading	0.9633	0.9352	0.9668
C4-5 Grading	0.9638	0.5153	0.8529
C5-6 Grading	0.9393	0.4571	0.9984
C6-7 Grading	0.9517	0.9446	1.0
C7-T1 Grading	0.9794	0.9099	0.9998
Combined Score	0.9875	0.88	0.9999
Highest Grade	0.8551	0.3727	0.9942

Multivariate models were used to determine relationships to cervical spine DDD, adjusting for multiple factors. Self-pay and Medicare insurance, older age and increased ASA were found to be significantly associated with increased cumulative grade of DDD using the multivariate model (Table 5). Surprisingly, diabetes status (Supplementary Appendix C) and BMI were not associated with increasing cumulative grade or severity of DDD, when adjusting for other factors.

Table 5 Multivariate linear regression model identifying.

Suzuki Grading	Comorbidities	Risk Level	Estimate	Std. Error	P-value	P-value Significance
Cumulative grade	Age		0.0521	0.0096	0	1
	Insurance	Medicare	1.2148	0.3087	0.0001	1
	Insurance	Medicaid	0.1236	0.3617	0.7326	0
	Insurance	Tricare	−1.9393	1.1508	0.0926	0
	Insurance	VA Fee Basis	1.7804	0.9535	0.0625	0
	Insurance	Worker's Comp	0.2643	0.9106	0.7717	0
	Insurance	Self-pay	−2.9437	0.6478	0	1
	Insurance	Other	0.4137	0.8318	0.6192	0
	ASA class	2	2.6538	1.1543	0.0219	1
	ASA class	3	2.8949	1.1511	0.0122	1
	ASA class	4	2.9400	1.2066	0.0152	1
	Diabetes	Yes	0.4947	0.2579	0.0556	0

4 Discussion

The data from this study allowed for our hypothesis to be accepted due to multiple patient-related factors having strong associations with increased severity and cumulative grade of cervical spine disc degeneration. This study provided evidence for aging, specific medical comorbidities, insurance status, and socioeconomic variables being linked to grade and severity of cervical spine DDD. Increased cumulative grade of cervical spine DDD was associated with patient demographics (older age, decreasing median household income, previous cervical spine surgery, and Medicare insurance) and medical comorbidities (ASA classification, cancer, COPD, depression, diabetes, hypertension, hypothyroidism, peripheral vascular disease, and smoking) based on bivariate analyses. Interestingly, only non-white race was associated with a higher severity of disc degeneration without an increasing cumulative grade of cervical spine disc disease. These risk factors (increasing age, diabetes, hypertension, and hypothyroidism) match some of those previously reported increasing lumbar spine DDD.²^,⁵^,⁶^,⁹^,¹⁰

However, to our knowledge, cancer, COPD, and median household income have not previously been linked to DDD in either the lumbar or cervical spine.^3–9^,¹⁸ Further, bivariate analysis found an association between depression and higher grade and severity of cervical spine disc degeneration, which is consistent with previous studies showing a strong link between neck and back pain and depression¹⁹^,²⁰ and may be a manifestation of the psychological burden of chronic pain. For the present study, multivariate analyses demonstrated older age, Medicare insurance, self-pay insurance status, and higher ASA classification to be significantly associated with increased grade of cervical spine DDD, while diabetes was no longer significantly associated when adjusting for other factors. Older age and self-pay insurance were also associated with increased severity of cervical spine DDD based on multivariate analyses.

Taking the results of the present study together with previous studies focused on lumbar spine DDD, it seems likely that aging and an accumulation in related medical comorbidities increase the grade and severity of disc disease throughout the spine as a result of genetic, environmental, inflammatory, and degradative mechanisms of disease.⁷^,^21–24 Interestingly, bivariate analysis demonstrated diabetes mellitus was associated with DDD, but diabetes-control status did not appear to influence severity of DDD in the cervical spine. These results contrast those of Liu et al. who reported that uncontrolled diabetes increased lumbar spine disc degeneration and the length of time living with diabetes further increased disc degeneration.²⁵ The associations noted between decreasing median household income and self-pay insurance association with cervical spine disc degeneration may involve related vocations including manual labor, which entail higher risks of DDD throughout the spine.²⁶ However, this requires further study.

Due to the retrospective nature of this study there were multiple limitations inherent needing discussion. First, we were reliant on the accuracy of the information provided in the EMR including the accuracy of the medical comorbidities present at the time of MRI. We did not specifically design the study to assess associations between all medical comorbidities and grade of cervical spine DDD. Additionally, when looking at numerous comorbidities and their association with cumulative grade and severity of disc disease there is a higher likelihood that a comorbidity will be associated with disc disease by pure happenstance (type I error). We attempted to mitigate this error by using the Benjamini-Hochberg correction for multiple comparisons. In addition, the present study captured all patients undergoing cervical spine MRI in our healthcare system during the study period in order to mitigate selection bias when patients seen only by spine practitioners are included. Finally, we did not evaluate pain or patient-related outcomes. We were therefore unable to correlate the level of disc degeneration with disability or overall pain to determine the effects of medical comorbidities on symptomatic disc degeneration. Additional well-designed prospective or retrospective studies correlating the cumulative grade and severity of disc degeneration to medical comorbidities can strengthen our understanding of triggering events causing disc degeneration.

5 Conclusion

Cervical spine DDD is associated with patient-related variables that influence its cumulative grade and severity, many of which are similar to those established for lumbar spine DDD. Based on bivariate and multivariate analyses, there was strong evidence supporting older age, insurance status, and higher ASA classification to be significantly associated with increased grade of cervical spine DDD. Diabetes was strongly associated with higher grade and severity of cervical spine DDD when assessed as an independent risk factor, but diabetes-control status did not, and when accounting for other medical comorbidities, diabetes no longer had significant associations. However, it should be noted that the study design did not allow for determination of causation or even direct links between these variables and cervical spine DDD. Still, this study highlights the importance of patient demographics and medical comorbidities in influencing grade and severity of cervical spine disc degeneration, providing new evidence for education and treatment of patients at risk for cervical spine disorders.

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Author contributions statement

All authors were instrumental in study design, acquisition and analysis of study data, manuscript drafting, and final approval of all manuscript-related items.

Disclaimer

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

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