Authors: Kevin Yoon, Mumin Sabha, Theodore Quan, Vu Bui, Linus Lee, Christopher P. Bellaire, Mark Ehioghae, Jonathan P. Japa, Addisu Mesfin
Categories: Clinical Study, Ankylosing spondylitis, Diffuse idiopathic skeletal hyperostosis, Spinal fracture, Spinal fusion, Cervical spine, Noncervical fractures spine
Source: North American Spine Society Journal
Authors: Kevin Yoon, Mumin Sabha, Theodore Quan, Vu Bui, Linus Lee, Christopher P. Bellaire, Mark Ehioghae, Jonathan P. Japa, Addisu Mesfin
Ankylosing spondylitis (AS) and diffuse idiopathic skeletal hyperostosis (DISH) are 2 distinct spondyloarthropathies characterized by progressive spinal ankylosis. Despite their differing pathophysiologies, both conditions create long rigid spinal segments that are vulnerable to unstable fractures. Although the existing literature often examines postoperative outcomes of either AS or DISH-related fractures, direct comparisons between the 2 disorders remains limited. This study aims to compare 3-month, 1-year, and 2-year outcomes following spinal fusion for cervical and noncervical fractures in patients with AS and DISH.
This was a retrospective cohort study. The TriNetX Global Collaborative Network database was queried using ICD-10 and CPT codes to identify adult patients (≥18 years) diagnosed with either AS or DISH who underwent spinal fusion surgery following cervical or noncervical fractures spinal fractures within the past twenty years. Propensity score matching (1:1) was performed using demographic variables and relevant comorbidities. Postoperative complications were assessed at 3-month, 1-year, and 2-year intervals and included medical, surgical, and infection-related outcomes. All statistical analyses were performed within the TriNetX platform, and a p-value < .05 was considered statistically significant.
Among AS patients, the cervical group exhibited a significantly lower rate of surgical site infections (SSI) at 3 months (RR 0.44, p = .016), reduced thromboembolic events (RR 0.53, p = .03) at 2 years compared with AS patients with a noncervical fractures fracture. For both AS and DISH patients, cervical fractures were significantly associated with increased risk of spinal cord injury at all time points. In DISH patients, postoperative limb paralysis was also significantly higher following cervical fracture and fixation at all time points. Comparing all AS versus DISH patients, AS was associated with significantly higher mortality at 3 months (RR 2.16, p < .001), 1 year (RR 1.77, p < .001), and 2 years (RR 1.73, p < .001). Instrumentation failure was more common in AS patients at 1 year (RR 2.27, p = .018) and 2 years (RR 1.93, p = .032). Interestingly, pseudoarthrosis was significantly less common in AS compared to DISH at 1 year (RR 0.58, p = .006) and 2 years (RR 0.59, p = .0065).
Cervical fractures in both AS and DISH patients showed a higher risk of SCI compared to noncervical fractures, likely secondary to the narrowing of the canal within this region. Overall, AS patients had higher rates of mortality, instrumentation failure, and wound complications compared to those with DISH, while DISH patients had higher rates of pseudoarthrosis.
Ankylosing spinal disorders (ADs) are a group of conditions characterized by pathological spinal ossification and progressive loss of spinal mobility [[1], [2], [3], [4]]. In the spine of patients with ADs, abnormal bony fusion of vertebral segments forms a long lever arm that inadequately diffuses mechanical forces [5,6]. Due to the impaired compensatory mechanical properties, minor traumas can cause unstable vertebral fractures [5,7]. These unstable fractures are associated with significantly higher rates of complications such as spinal cord injuries and delayed neurologic degeneration, as delayed recognition, inadequate immobilization, or improper transfers can further compromise the spinal canal [[5], [8], [9], [10], [11]]. Historically, nonoperative management of spinal fractures in patients with ADs have been linked with increased morbidity and mortality, thus surgical management is preferred [[12], [13], [14]].
Ankylosing spondylitis (AS) and diffuse idiopathic skeletal hyperostosis (DISH) are the 2 major etiologies of ADs which have become increasingly prevalent [15]. Both conditions result in rigid, hyperostotic spines, but arise from different pathophysiologic processes. AS is an inflammatory spondyloarthropathy involving progressive ossification, with a characteristic preference for the sacroiliac joints, syndesmophyte formation, and fusion of the posterior elements [1,5]. In contrast, DISH is a noninflammatory process commonly affecting the thoracic spine, characterized by flowing ossification of the anterior longitudinal ligament and relative preservation of the intervertebral disc space [2,16].
Although the existing literature often examines postoperative outcomes of either AS or DISH-related fractures, direct comparisons between the 2 disorders remains limited, particularly when taking into account the spinal region [14]. The present study primarily aims to evaluate the postoperative outcomes in patients with AS or DISH following spinal fusion for vertebral fractures at the 3-month, 1-year, and 2-year mark. Secondarily, the study compares how fractures in the cervical or noncervical fractures region may impact perioperative outcomes. The null hypothesis was that there was no difference in outcomes between the 2 cohorts (Fig. 1, Fig. 2).Fig. 1Fracture in patients with cervical ankylosing spondylitis (AS). Can see ossification of the anterior spine spanning multiple cervical levels. Importantly, AS can invade into the intervertebral space, indicated by loss of disc height at multiple levels. Diagnosis requires (1) bilateral sacroiliitis with or without uveitis, and a positive HLA-B27 blood marker.Fig 1 dummy alt textFig. 2Thoracic fracture in patient with diffuse idiopathic skeletal hyperostosis (DISH). Criteria for diagnosis criteria include flowing (1) ossification along the anterolateral aspect of at least 4 contiguous vertebrae, (2) preservation of disc height of involved vertebrae segments and relative absence of significant degenerative changes; (3) absence of facet-joint ankylosis and absence of SI joint involvement.Fig 2 dummy alt text
This was a retrospective cohort study performed using the TriNetX Global Collaborative Research Network database. TriNetX is a federated database that aggregates deidentified patient information from electronic health records from a large group of health care organizations within the United States. Data available includes demographics, diagnoses, medications, and procedures. As the study uses deidentified patient data, ethical approval was waived by the Institutional Review Board.
Using International Classification of Diseases-9/10 (ICD-9/10) and current procedural terminology (CPT) codes, adults aged 18 years or older diagnosed with either AS or DISH who underwent posterior spinal fusion surgery following cervical or noncervical fractures spinal fractures within the past twenty years were identified. Only primary fractures and posterior fusions were included. Fractures must have occurred within 3 months prior to the posterior fusion surgery. To remove potentially staged procedures, patients with an anterior approach fusion within 3 months before or after the index posterior event were excluded. Patients were divided into cohorts based on hyperostotic pathology and fracture location (cervical vs. noncervical fractures). Due to limitations in cohort size, thoracic and lumbar fractures were grouped together.
A total of 753 AS patients with fractures and 806 DISH patients with fractures were included. To minimize baseline variability between groups, propensity score matching (1:1) was performed based on age at index surgery, obesity, nicotine dependence, diabetes mellitus, presence of chronic obstructive pulmonary disease (COPD), gender, and race. TriNetX utilizes a greedy nearest-neighbor matching system with a 0.1 caliper width. Missing data was excluded from analysis, and patients lost to follow-up were excluded at analysis of that specific time point.
Postoperative complications were evaluated at 3 months, 1 year, and 2 years following spinal fusion. Medical complications included thromboembolic events (both deep vein thrombosis and pulmonary embolism), urinary tract infection, and other medical events requiring emergency department (ED) visitation or inpatient management. Neurological complications such as cervical nerve root injury, limb paralysis, and spinal cord injury were also evaluated. Surgical complications included revision surgery, surgical site infection, wound complication, and instrumentation failure. Long term structural outcomes such as pseudoarthrosis and secondary cervical or lumbar fractures were collected when available. Mortality was assessed at all time points. All outcome coding were from prior published literature using the TriNetX database [[17], [18], [19]].
All statistical analyses were performed within the TriNetX platform using built-in analytical tools. Risk ratios were calculated for cervical versus noncervical fractures within the AS and DISH groups, as well as for AS compared with DISH across the fracture locations. Hazard ratio was calculated for mortality. A p-value < .05 was considered statistically significant for all comparisons.
Prior to matching, a total of 753 AS patients with fractures and 806 DISH patients with fractures were identified. Average age at index for AS patients was 68 (SD: 13.2) years old, 648 were male, and 615 were white. Of the 753 patients included, only 33 had an active prescription for adalimumab, 18 had a prescription for etanercept, and less than 10 had a prescription for golimumab or infliximab. Average age for DISH patients was 71.7 (10.9) years old, 692 were male, and 640 were white. Following 1 propensity score matching based on demographics and relevant risk factors, complete data was described for 576 AS and DISH patients. On average, the AS cohort was 68.0 ± 13.2 years old, 86.1% male, and 81.7% white. The DISH cohort was on average 71.7 ± 10.9 years old, 85.9% male, and 79.4% white. Patients were lost due to lack of follow-up available for all time points. Average follow up time at 90-days was 89 days for both groups, at 1-year was 350 days for both groups, and at 2-year was 678 days for AS patients and 703 days for DISH patients (Table 1).Table 1Demographic.Table dummy alt textVariablePre-PSMPost-PSMpSMDAS (n = 753)DISH (n = 806)AS (n = 576)DISH (n = 576)Age at index68 ± 13.271.7 ± 10.969 ± 1169 ± 10.6.930.005Male648692480493.280.064Female981139177.240.069Hispanic or Latino30402521.550.036White615640458460.80.009Black or AA55754749.830.013Hypertension373483307308.950.004Diabetes mellitus251371221217.810.014Hyperlipidemia244342217214.850.01Heart failure143168119118.940.004Obesity116173105100.70.02Depression9911985851< 0.001Anxiety981128277.670.025Chronic obstructive pulmonary disease89976871.790.016Nicotine dependence79755654.840.01
At 3 months, cervical fractures were associated with significantly lower risk of surgical site infection (SSI) compared with noncervical fractures (RR 0.44, 95% CI 0.22–0.88, p = .016) (Table 2). At 3 months and 1-year, cervical fractures were associated with significantly lower risk of thromboembolic events (3 RR 0.48, 95% CI 0.24–0.96, p = .033; 1 RR 0.53, 95% CI 0.3–0.95, p = .03). At 1-year, cervical fractures were associated with significantly higher risk of repeat fracture (RR 1.95, 95% CI 1.01–3.75, p = .044). Lastly, at all-time points, cervical fractures were associated with significantly higher risk of spinal cord injury compared to noncervical fractures (3 RR 1.73, 95% CI 1.10–2.72, p = .015; 1 RR 1.53, 95% CI 1.03–2.28, p = .034; 2 RR 1.53, 95% CI 1.03–2.28, p = .034) (Table 3, Table 4, Table 5, Table 6, Table 7).Table 2Propensity score matched inter-vertebral outcomes of all fractures in patients with AS.Table dummy alt text3 mo ASpVariableCervical (N = 278)Thoracic or lumbar (N = 278)RR95% CIRevision surgery13220.5910.304, 1.15.12Surgical site infection11250.440.221, 0.88.016Wound complication (dehiscence, infection, hematoma)14240.580.31, 1.10.092Hardware failureED visitation34271.260.78, 2.03.34Mortality31281.110.66, 1.84.7Spinal cord injury45261.731.10,2.72.015Cervical root injury00Urinary tract infection29261.120.68, 1.84.67Pseudoarthrosis28231.220.72, 2.05.46Secondary cervical fracture11131.650.76, 3.56.2Secondary lumbar fractureMedical complication38490.780.53, 1.14.19Thrombotic event11230.4780.24, 0.96.033Limb paralysis34311.10.70, 1.73.691-y ASRevision surgery13220.5910.304, 1.15.12Surgical site infection11250.440.221, 0.88.016Wound complication (dehiscence, infection, hematoma)15300.275, 0.910.5.02Hardware failureED readmission49431.147.9, 1.66.49Mortality41381.090.70, 1.7.69Spinal cord injury52341.531.03, 2.28.034Cervical root injury00Urinary tract infection39321.220.79, 1.88.37Pseudoarthrosis32281.140.71, 1.84.58Secondary cervical fracture16161.951.01, 3.75.044Secondary lumbar fractureMedical complication44560.790.55, 1.19.18Thrombotic event16300.530.3, 0.95.03Limb paralysis40331.20.79, 1.86.372-y ASRevision surgery13220.5910.3, 1.15.12Surgical site infection12260.460.24, 0.90.019Wound complication (dehiscence, infection, hematoma)16320.50.28, 0.89.016Hardware failure< 10130.770.34, 1.72.52ED readmission54511.060.75, 1.49.74Mortality46421.110.63, 1.69.63Spinal cord injury52341.531.03, 2.28.034Cervical root injuryUrinary tract infection41311.320.86, 2.04.2Pseudoarthrosis34311.0970.70, 1.73.69Secondary cervical fracture16201.550.84, 2.88.16Secondary lumbar fractureMedical complication47630.750.54, 1.04.08Thrombotic event17280.341, 1.0790.34, 1.08.085Limb paralysis37311.190.77, 1.86.43AS, ankylosing spondylitis.Table 3AS—propensity-score matched cervical versus thoracic only (N = 278).Table dummy alt textVariable3 mo1 y2 yRR95% CIpRR95% CIpRR95% CIpRevision surgery0.750.42, 1.35.340.810.47, 1.41.450.810.47, 1.4.45Surgical site infection0.580.3, 1.07.0750.620.35, 1.09.0950.610.35, 1.06.077Wound complication (dehiscence, infection, hematoma)0.730.43, 1.24.250.720.43, 1.20.20.730.44, 1.2.21Hardware failure10.44, 2.2710.80.38, 1.68.55ED visitation0.970.61, 1.54.891.040.74, 1.46.830.940.63, 1.28.69Mortality10.63, 1.5911.040.7, 1.51.821.060.75, 1.51.75Spinal cord injury1.020.69, 1.51.911.090.76, 1.56.661.060.74, 1.52.74Cervical root injuryUrinary tract infection0.940.59, 1.49.791.150.78, 1.69.491.110.77, 1.60.58Pseudoarthrosis10.54, 1.8510.870.53, 1.43.570.90.56, 1.47.68Secondary cervical fracture2.031.02, 4.05.042.171.16, 4.07.0132.281.22, 4,2.008Secondary thoracic or lumbar fractureMedical complication0.90.64, 1.25.5310.73, 1.3611.010.76, 1.36.92Thrombotic event0.640.33, 1.22.170.790.44, 1.41.430.710.41, 1.24.23Limb paralysis0.70.47, 1.11.140.790.52, 1.17.230.760.51, 1.15.19Table 4AS—propensity-score matched junctional versus nonjunctional outcomes (N = 201).Table dummy alt textVariable3 mo1 y2 yRR95% CIpRR95% CIpRR95% CIpRevision surgery1.630.79, 3.38.181.640.79, 3.38.17Surgical site infection1.550.74, 3.22.241.120.6, 2.09.731.170.64, 2.18.6Wound complication (dehiscence, infection, hematoma)1.570.83, 2.98.161.380.74, 2.5.311.440.78, 2.64.24Hardware failureED visitation0.880.50, 1.5.640.90.61, 1.39.71.050.72, 1.51.81Mortality1.420.79, 2.56.251.460.88, 2.52.141.140.77, 1.74.52Spinal cord injury0.830.5, 1.37.460.880.56, 1.39.580.910.58, 1.43.68Cervical root injuryUrinary tract infection1.260.72, 2.22.421.110.69, 1.8.671.210.77, 1.89.41Pseudoarthrosis1.640.79, 3.37.181.460.74, 2.87.27Medical complication1.621.07, 2.57.0211.350.93, 1.97.111.20.85, 1.67.3Thrombotic event0.670.33, 1.35.250.750.4, 1.4.380.820.45, 1.48.5Limb paralysis21.09, 3.68.021.710.97, 3.0.0591.771, 3.09.043Table 5Propensity score matched inter-vertebral outcomes of all fractures in patients with DISH.Table dummy alt text3 mo DISHpVariableCervical (N = 275)Thoracic or lumbar (N = 275)RR95% CIRevision surgeryNot enoughSurgical site infection19210.910.5, 1.65.74Wound complication (dehiscence, infection, hematoma)23250.920.54, 1.58.76Hardware failureNot enoughED admission34380.90.58, 1.38.61Mortality30221.380.80, 2.40.25Spinal cord injury55222.51.57, 4.0< .001Cervical root injury00Urinary tract infection31400.780.5, 1.2.25Pseudoarthrosis181810.53, 1.881Medical complication41550.750.52, 1.08.12Thrombotic event15250.60.32, 1.11.1Limb paralysis35152.331.3, 4.17.0031-y DISHRevision surgery11130.850.39, 1.86.68Surgical site infection22201.10.62, 1.97.75Wound complication (dehiscence, infection, hematoma)22260.850.49, 1.46.55Hardware failureNot enoughED admission51530.960.68, 1.36.83Mortality42281.550.96, 2.5.07Spinal cord injury60282.141.41, 3.25< .001Cervical root injury00Urinary tract infection41430.950.64, 1.41.81Pseudoarthrosis24221.090.63, 1.90.76Medical complication48490.980.68, 1.41.91Thrombotic event22240.920.53, 1.59.76Limb paralysis4172.411.41, 4.14< .0012-y DISHRevision surgery11140.790.36, 1.7.54Surgical site infection22230.960.55, 1.68.88Wound complication (dehiscence, infection, hematoma)25270.930.55, 1.56.77Hardware failureNot enoughED admission66680.970.72, 1.31.84Mortality47371.30.85, 2.01.23Spinal cord injury59262.271.47, 3.50< .001Cervical root injury00Urinary tract infection43500.860.59, 1.25.43Pseudoarthrosis24221.090.63, 1.90.76Medical complication52640.810.59, 1.13.21Thrombotic event22280.790.46, 1.34.37Limb paralysis39172.291.33, 3.96.0019DISH, diffuse idiopathic skeletal hyperostosis.Table 6DISH—propensity-score matched cervical versus thoracic only (N = 275).Table dummy alt textVariable3 mo1 y2 yRR95% CIpRR95% CIpRR95% CIpRevision surgery0.820.41, 1.65.580.880.45, 1.74.71Surgical site infection0.960.54, 1.69.880.920.52, 1.61.760.820.48, 1.4.47Wound complication (dehiscence, infection, hematoma)0.910.57, 1.46.690.910.58, 1.44.70.830.53, 1.28.39Hardware failureED visitation1.220.85, 1.76.281.10.82, 1.46.521.080.84, 1.39.55Mortality1.440.94, 2.2.091.421, 2.02.0491.51.07, 2.1.017Spinal cord injury1.931.35, 2.74< .0011.781.27, 2.49< .0011.81.29, 2.52< .001Cervical root injuryUrinary tract infection1.30.85, 2.231.290.9, 1.85.171.220.87, 1.71.26Pseudoarthrosis1.070.54, 2.13.851.40.77, 2.58.261.260.7, 2.27.43Secondary cervical fracture3.31.65, 6.4< .0012.991.55, 5.76.006Secondary thoracic or lumbar fractureMedical complication0.920.65, 1.29.610.830.61, 1.11.220.810.61, 1.08.14Thrombotic event0.750.45, 1.25.270.830.53, 1.32.440.850.55, 1.31.46Limb paralysis2.211.32, 3.72< .0012.271.41, 3.67< .0012.321.44, 3.74< .001Table 7DISH—propensity-score matched junctional versus nonjunctional outcomes (N = 231).Table dummy alt textVariable3 mo1 y2 yRR95% CIpRR95% CIpRR95% CIpRevision surgerySurgical site infection0.830.43, 1.61.590.940.5, 1.78.5, 1.780.950.51, 1.76.86Wound complication (dehiscence, infection, hematoma)0.740.41, 1.34.320.960.55, 1.66.8810.58, 1.731Hardware failureED visitation0.960.58, 1.61.880.770.53, 1.13.180.80.57, 1.11.18Mortality1.070.53, 2.16.930.90.52, 1.56.630.930.56, 1.55.62Spinal cord injury1.260.76, 2.11.371.480.9, 2.42.121.641, 2.69.049Cervical root injuryUrinary tract infection1.0530.58, 1.92.870.730.42, 1.28.260.8440.52, 1.36.48Pseudoarthrosis1.250.60, 2.61.55Medical complication1.20.77, 1.88.431.060.7, 1.591.061.020.71, 1.48.91Thrombotic event1.190.63, 2.25.610.55, 1.811.280.71, 2.3.82Limb paralysis0.920.43, 1.98.840.720.36, 1.44.35
A sensitivity analysis was performed comparing cervical versus thoracic fractures only, and similar findings were seen. Cervical fractures were associated with a nonsignificant decreased risk of SSI was seen at 3-months (RR 0.58, 95% CI 0.3–1.07, p = .075), and 1-year (RR 0.62, 95% CI 0.35–1.09, p = .095). Cervical fractures were also associated with a nonsignificant decrease in thrombotic events at 3-months (RR 0.64, 95% CI 0.33–1.22, p = .17) and 1-year (RR 0.79, 95% CI 0.44–1.41, p = .43), and associated with a significantly increased risk of subsequent cervical fracture at all time points.
A subanalysis was also performed reviewing junctional versus nonjunctional fractures by identifying patients with fractures in 2 adjacent vertebral segments (eg cervical and thoracic or thoracic and lumbar). Notably, junctional fractures were associated with a significantly higher risk of medical complications (RR 1.62, 95% CI 1.07–2.57, p = .021) at 3 months, and significantly higher risk of limb paralysis at all time points.
At all-time points, cervical fractures were associated with significantly higher risk of spinal cord injury (3 RR 2.5, 95% CI 1.57–4.00 p < .001; 1 RR 2.14, 95% CI 1.41–3.25, p < .001; 2 RR 2.27, 95% CI 1.47–3.50, p < .001) and significantly higher risk of limb paralysis at all time points (3 RR 2.33, 95% CI 1.3–4.17, p = .003; 1 RR 2.41, 95% CI 1.41–4.14, p < .001; 2 RR 2.29, 95% CI 1.33–3.96, p = .002).
A sensitivity analysis was performed reviewing cervical versus thoracic fractures only, and like results were found. Cervical fractures were associated with significantly higher risk of spinal cord injury and limb paralysis at all time points. Notably, on subanalysis, cervical fracture patients were associated with an increased risk of subsequent cervical fracture at 1-year (RR 3.3, 95% CI 1.65–6.4, p < .001) and 2-year (RR 2.99, 95% CI 1.55–5.76, p < .001).
A subanalysis comparing junctional versus nonjunctional injuries displayed no significant differences in outcomes, except a significant association with an increased risk of spinal cord injury at 2-years after injury within the junctional cohort (RR 1.64, 95% CI 1–2.69, p = .049). Results can be seen in Table 5.
At all-time points, patients with AS had significantly higher risk of mortality (3 RR 2.16, 95% CI 1.46–3.2, p < .001; 1 RR 1.77, 95% CI 1.30–2.40, p < .001; 2 RR 1.73, 95% CI 1.30–2.29, p < .001). At 3 months, patients with AS were associated with risk of subsequent surgery (RR 2.25, 95% CI 1.15–3.49, p = .015). At 1 year and 2 years, patients with AS were associated with increased risk of instrumentation failure (1 RR 2.27, 95% CI 1.13–4.60, p = .018; 2 RR 1.93, 95% CI 1.05–3.57, p = .032). Conversely, at 1 year and 2 years, patients with AS were associated with significantly lower risk of pseudoarthrosis (1 RR 0.58, 95% CI 0.39–0.86, p = .006; 2 RR 0.59, 95% CI 0.40–0.87, p = .007). Results can be seen in Table 8.Table 8Postpropensity matched outcomes of all fractures in patients with DISH or ASK.Table dummy alt text3 mopVariableASK (n = 576)DISH (n = 576)OR95% CIRevision surgery27122.251.15,.015Surgical site infection363610.64, 1.561Wound complication (dehiscence, infection, hematoma)52421.240.84, 1.83.28Hardware failureNot enoughED readmission74760.970.72, 1.3.86Mortality77372.161.46, 3.2< .001Cervical root injuryUrinary tract infection75681.140.83, 1.55.42Pseudoarthrosis29440.660.42, 1.04.07Secondary cervical fracture19220.820.45, 1.50.53Secondary lumbar fractureMedical complication1181031.150.9, 1.45.26Thrombotic event40391.030.67, 1.57.91Limb paralysis63481.310.92, 1.88.131-yRevision surgery34241.420.85, 2.36.18Surgical site infection44470.940.63, 1.39.74Wound complication (dehiscence, infection, hematoma)61511.20.84, 1.71.32Hardware failure25112.271.13, 4.6.018ED visitation1031130.910.72, 1.16.45Mortality112661.771.30, 2.40< .001Spinal cord injury96911.10.81, 1.37.69Cervical root injuryNot enoughUrinary tract infection90841.070.82, 1.41.62Pseudoarthrosis36620.580.39, 0.86.006Secondary cervical fracture27260.990.59, 1.67.97Secondary lumbar fracture17131.480.74, 2.97.27Medical complication1351141.180.95, 1.48.13Thrombotic event53501.060.73, 1.53.76Limb paralysis70551.270.911, 1.78.152-yRevision surgery36271.330.82, 2.17.24Surgical site infection45500.90.61, 1.33.59Wound complication (dehiscence, infection, hematoma)62531.170.83, 1.66.38Hardware failure29151.931.05, 3.57.032ED readmission1221390.880.71, 1.09.24Mortality127771.731.3, 2.29< .001Spinal cord injury96931.030.79, 1.34.81Urinary tract infection91951.040.80, 1.36.75Pseudoarthrosis37630.590.40, 0.87.0065Secondary cervical fracture28270.990.59, 1.65.97Secondary lumbar fracture17141.380.70, 2.72.36Medical complication1461231.190.96, 1.47.11Thrombotic event56511.10.77, 1.57.61Limb paralysis71571.250.9,0, 1.73.19DISH, diffuse idiopathic skeletal hyperostosis; ASK, ankylosing spondylitis.
In this propensity scorematched cohort study of patients with AS or DISH undergoing spinal fusion for cervical or noncervical fractures, several important differences in postoperative outcomes based on both hyperostotic pathology and fracture location were identified. Cervical fractures were associated with a significantly higher risk of neurologic complications in both disorders. Additionally, AS was associated with significantly greater risk of mortality and instrumentation failure, while DISH was associated with higher long-term risk of pseudoarthrosis.
In both AS and DISH cohorts, cervical fractures were associated with a significantly increased risk of spinal cord injury (SCI) compared to noncervical fractures at all time points. Most acute spinal fractures in patients with ADs occur in the subaxial cervical spine, particularly at C5-C6 and C6-C7 [5,20,21]. This region is especially susceptible due to a relatively narrow canal diameter [5,15,20]. As a result, even marginally displaced fractures can compromise the spinal cord and lead to damage [15]. Additionally, diagnosis of cervical fractures is often delayed due to nonspecific presentation and relatively low radiographic sensitivity [20,22]. Our findings shows that SCI risk persists beyond the immediate postoperative period and supports a low threshold for obtaining advanced imaging in AD patients with possible cervical spine injury, as well as heightened postoperative monitoring.
Interestingly, peri‑operative complications differed between AS and DISH patients, which may be reflective of the different comorbidity profiles correlated with these pathologies. AS is a well-known B27-related autoimmune condition commonly associated with poor wound healing and subsequent complications such as infection or dehiscence [[23], [24], [25]]. The exact mechanism for higher thromboembolic events has yet to be clearly defined within AS patients. However, a link between elevated inflammatory cytokines correlating with hyperstimulation of the coagulation cascade has been postulated [26,27]. Both findings point towards further research into peri‑operative management of patients regarding wound care, antibiotic use, and thromboembolic prophylaxis.
In the DISH cohort, patients with cervical fractures had significantly higher risk of limb paralysis compared to patients with noncervical fractures. Literature has highlighted how delayed detection of cervical fractures within DISH patients specifically have led to worse neurologic outcomes [[28], [29], [30]]. Our findings support prior findings and indicate a need for advanced imaging for any cervical trauma in DISH patients, while a noncervical fractures injury may warrant further work-up on a case-by-case basis.
Our findings add to the mixed data regarding differences in mortality between AS and DISH [5,11,31,32]. A possible explanation for the observed difference in mortality is the distinct comorbidity profiles of the 2 conditions. AS is an inflammatory spondyloarthropathy associated with restricted pulmonary physiology, cardiovascular disease, and osteoporosis, all of which can magnify surgical stress [[33], [34], [35], [36], [37], [38], [39]]. In contrast, DISH is linked to metabolic comorbidities like obesity and diabetes, which are clinically relevant but may not affect the cardiopulmonary reserve as strongly postoperatively [40]. Alternatively, fracture location may play a large role. Schoenfeld et al. emphasized the high risk of morbidity in cervical fractures, even within their smaller sample size [24]. Within our study cohorts, there were over 100 cervical fractures noted within the AS patient sample, likely contributing to the exorbitantly high mortality rates within the group. Our study however is limited by the lack of detail regarding etiology of trauma. With an inherent risk of fracture within this patient group, future research on how mechanism of injury impacts outcomes may help clarify the varying mortality rates seen in the literature. Pharmacologic differences may also play a role. Treatment of AS has evolved to include tumor necrosing factor (TNF)-alpha inhibitors, which may increase risk for immunity and overall health by decreasing the inflammatory cascade and cytokine production. However, past studies have been mixed on the actual effects of TNF-alpha inhibitors on wound healing. For instance, a meta-analysis performed by Xu et al. looking at risk of infection in patients with AS or spondyloarthritis found a nonsignificant increase in risk of infection, indicating potential bias within their studies [41]. A meta-analysis performed by Liu et al. also found there was an overall significant increase in patients using TNF-alpha inhibitors within elective orthopaedic surgery, but many individual studies included did not see a difference, and the effect was typically seen only in patients with preoperative TNF-alpha usage [42]. As noted within their article, there was a lack of randomized prospective studies on the topic, and available research has been performed within a rheumatoid arthritis population—which at baseline may have an increased risk for infection than the ankylosing spondylitis patient population. Due to the limited research, the role of TNF-alpha on outcomes cannot be ascertained, especially within the current study where a limited group of patients had an active prescription at any time prior to the index operation.
AS patients further exhibited higher rates of instrumentation failure at 1 and 2 years compared to DISH patients. This difference is likely attributable to the biomechanical and physiologic characteristics of AS. AS is associated with severe osteoporosis and long-segment ankylosis [38]. This can reduce the ability to securely anchor spinal implants and dissipate physiologic loads. In contrast, DISH often presents with more localized anterior ossification and relatively preserved posterior elements, resulting in a less globally fused spine that can distribute forces more favorably than in AS [2]. This finding suggests a need for research reviewing preoperative and intraoperative optimization for AS patients for improved instrumentation stability.
DISH patients were found to have significantly higher rates of pseudoarthrosis compared with AS patients at 1 year and 2 years in the combined noncervical fractures cohorts, likely related to the metabolic comorbidities associated with DISH, such as obesity and diabetes, which are known to impair bone healing [40]. Notably, GLP-1 agonists are commonly prescribed to address these common comorbidities. Research regarding the impact of this medication and how it interacts with the pathology of DISH postoperatively may be worthwhile to see how it affects bony outcomes.
This study contains several limitations. First, clinical details such as mechanism of injury, surgical approach, and fracture morphology are not evaluated in the dataset and can impact surgical outcomes, and thus our study is limited to an association rather than any causal relationship or conclusion between pathology and outcomes reported. The power of the analysis is dependent on the accuracy of billing codes, and miscoding or noncoding by providers are potential sources of error. DISH and AS can easily be mistaken on x-ray, CT, or MRI, and thus creates room for interobserver error—which cannot be accounted for within the current study. To best amend this problem, groups were created by excluding those with any future or prior diagnosis of the other pathology at any time point (eg if diagnosed with DISH they cannot have any diagnosis of AS in their chart either before or after index event, and vice-versa).
Additionally, the nature of the TriNetX database does not clearly illustrate which patients were lost to follow-up versus which simply had delayed follow-up. Although 1 propensity score matching was performed, unmeasured confounders may still be present. There has been an increased trend towards percutaneous pedicle screws for the management of thoracic and lumbar stiff spine fractures, and those details are not captured in the TrinetX database [13,[43], [44], [45]]. Lastly, the data does not include information about airway management and intubation difficulties during surgery, which is a known issue in AD patients and can contribute to morbidity or mortality [46,47]. Thus, external validity of our findings is limited.
In this study, fracture location and underlying AD were found to be correlated with postoperative outcomes after spinal fusion. Cervical fractures in both AS and DISH patients showed a higher risk of SCI compared to noncervical fractures, demonstrating the vulnerability of the ankylosed cervical spine. Overall, AS patients had higher rates of mortality, instrumentation failure, and wound complications compared to those with DISH, while DISH patients had higher rates of pseudoarthrosis. These differences highlight the distinct biomechanical characteristics of each disorder and the importance of considering pathology and fracture site when treating and counseling patients. Further investigation incorporating imaging and surgical variables is needed to better understand the mechanisms behind these outcomes and guide surgical decision making.
Data is available upon reasonable request to the corresponding author.
Authors A.M, L.L, T.Q contributed to curation and supervision of the study. Authors M.S, K.Y, M.E, V.B, J.P.J completed data collection/analysis and manuscript formulation. All Authors (M.S, K.Y, M.E, T.Q, V.B, L.L, J.P.J, A.M) supported editing and submission of the study.
Addisu Mesfin following conflict of Grants from Nuvasive, OREF grant, Depuy speaking fees, Globus consulting. The remaining co-authors have no conflict of interest to declare.