Abstract
Study Design.
Heterogeneous data collection through a mix of prospective, retrospective, and ambispective methods.
Objective.
To evaluate the effect of biological sex on patient-reported outcomes after spinal fusion surgery for lumbar degenerative disease.
Summary of Background Data.
Current literature suggests sex differences regarding clinical outcome after spine surgery may exist. Substantial methodological heterogeneity and limited comparability of studies warrants further investigation of sex-related differences in treatment outcomes.
Materials and Methods.
We analyzed patients who underwent spinal fusion with or without pedicle screw insertion for lumbar degenerative disease included within a multinational study, comprising patients from 11 centers in seven countries. Absolute values and change scores (change from preoperative baseline to postoperative follow-up) for 12-month functional impairment [Oswestry disability index (ODI)] and back and leg pain severity [numeric rating scale (NRS)] were compared between male and female patients. Minimum clinically important difference (MCID) was defined as >30% improvement.
Results.
Six-hundred sixty (59%) of 1115 included patients were female. Female patients presented with significantly baseline ODI (51.5±17.2 vs. 47.8±17.9, P<0.001), back pain (6.96±2.32 vs. 6.60±2.30, P=0.010) and leg pain (6.49±2.76 vs. 6.01±2.76, P=0.005). At 12 months, female patients still reported significantly higher ODI (22.76±16.97 vs. 20.50±16.10, P=0.025), but not higher back (3.13±2.38 vs. 3.00±2.40, P=0.355) or leg pain (2.62±2.55 vs. 2.34±2.43, P=0.060). Change scores at 12 months did not differ significantly among male and female patients in ODI (∆1.31, 95% CI: -3.88 to 1.25, P=0.315), back (∆0.22, 95% CI: -0.57 to 0.12, P=0.197), and leg pain (∆0.16, 95% CI: -0.56 to 0.24, P=0.439). MCID at 12 months was achieved in 330 (77.5%) male patients and 481 (76.3%) female patients (P=0.729) for ODI.
Conclusion.
Both sexes experienced a similar benefit from surgery in terms of relative improvement in scores for functional impairment and pain. Although female patients reported a higher degree of functional impairment and pain preoperatively, at 12 months only their average scores for functional impairment remained higher than those for their male counterparts, while absolute pain scores were similar for female and male patients.
Key Words: predictive analytics, outcome prediction, spinal fusion, neurosurgery, clinical prediction model
Lumbar degenerative disease (LDD) is a leading cause of severe disability on a global scale.1 Increasing evidence suggests that sex-related differences may play a role in the pathophysiology, presentation, and clinical course of LDD.2–4 However, conflicting data in the literature make it difficult to ascertain the existence of or effect size for sex differences in postoperative outcome.
Several studies proposed that female patients experience a higher degree of functional impairment, which may be due to anatomic-physiological differences,5 increased pain perception6 and a heightened inflammatory response.7,8 Consistent with that, female sex has frequently been identified as a predictive factor for worse postoperative pain, higher disability, and inferior quality of life.9–13 A recent review by MacLean et al.14 concluded that 80% of studies found that females had worse absolute postoperative scores measuring pain, disability or quality of life, and about 73% of studies reported an equivalent or greater degree of improvement between genders. Problematically, the majority of these studies were retrospective single-center analyses and therefore represented level IV evidence. According to this review, nine thematically relevant prospective studies have been published so far, all of which were single-center studies apart from one that analyzed the data of two centers in one country. However, effect sizes might vary substantially across different populations, health systems, and surgical procedures which renders it difficult to draw valid and generalizable conclusions from single-center analyses studying a single procedure.
Quantifying the effect of sex on postoperative outcome after spinal fusion surgery could inform clinical decision-making and optimize treatment strategies. In this study, we therefore aimed to analyze the effect of sex on patient-reported outcomes in patients undergoing spinal fusion surgery for LDD in a large multinational, multicenter cohort.
MATERIALS AND METHODS
Patient Population
A data set of a multinational study comprising patient data from 11 centers in seven countries (FUSE-ML15) was analyzed. Four centers (484 patients) provided prospective data, five centers (455 patients) retrospective data, and two centers (176 patients) mixed data. Patients who underwent spinal fusion with or without thoracolumbar pedicle screw placement, for degenerative pathologies [one or multiple of the following: spinal stenosis, spondylolisthesis, degenerative disc disease, disc herniation, failed back surgery syndrome (FBSS), radiculopathy, pseudarthrosis] were included. Exclusion criteria encompassed: surgery as the primary indication for infections, vertebral tumors, traumatic and osteoporotic fractures or deformity surgery for scoliosis or kyphosis; moderate or severe scoliosis (Coronal Cobb angle >30 degrees/Schwab classification sagittal modifier + or ++); surgery spanning more than six vertebral levels; missing endpoint data at 12 months; lack of informed consent; age below 18 years.
Data Collection
Data in each center were extracted retrospectively, from a prospective registry, or collected in a prospective registry and supplemented (S1, Supplemental Digital Content 1, http://links.lww.com/BRS/C549) by retrospectively collected variables, with 12-month follow-up. The following data were collected: age, biological sex, surgical indication, index level(s), height, weight, BMI (body mass Index), smoking status, American Society of Anesthesiologists (ASA) Score, preoperative use of opioid pain medication, bronchial asthma as a comorbidity, prior thoracolumbar spine surgery, race/ethnicity, surgical approach, pedicle screw insertion and minimally invasive technique. Patient-reported outcome measures (PROMs) were evaluated at baseline and at 12 months follow-up and encompassed Oswestry disability index (ODI) (scaled from 0 to 100) or core outcome measures index (COMI) for multidimensional subjective functional impairment, momentary numeric rating scale (NRS) for back pain severity, and NRS for leg pain severity.16,17 COMI scores were converted into ODI scores according to a previously published function.18 This study was approved by their local institutional review board (IRBs) at each study site, and data sharing statements were provided by all centers. Depending on the regulation of the local IRB, patients either provided written informed consent (in the case of prospective data collection), or the need for informed consent was waived (for retrospective data collection of pre-existing data).
Primary Endpoint Definitions
Clinically relevant improvements in ODI or NRS back and leg pain were dichotomized using the minimally clinically important difference (MCID) according to the validated threshold by Ostelo et al.16 (improvement in ODI and NRS pain severity by 30% from baseline to 12 mo postoperatively).
Statistical Analysis
Data were analyzed using R, version 4.2.2 (R Foundation for Statistical Computing, Vienna, Austria).19 Due to the low number of missingness, complete case analysis was performed. Continuous and categorical variables were reported as means (SDs) and absolute frequencies (percentages), respectively. Student t test and χ2 test were performed to test for intergroup differences. Change scores were defined as the degree of improvement from baseline up to 12 months. We controlled for age, smoking status, ethnicity, indication for surgery, minimally invasive surgery, pedicle screw insertion by including them as independent variables in multivariable logistic regression for sex, with MCID as the dependent variable. P-values <0.05 on two-sided tests were considered statistically significant.
RESULTS
Patient Cohort
Overall, data from 1115 patients were provided by 11 participating centers in total. Of them, 660 (59%) patients were female. Baseline demographic and disease-specific characteristics are displayed in Table 1. Female patients were significantly older (61.9±12.1 vs. 59.2±12.8, P<0.001), were more frequently nonsmokers (61.4% vs. 44.4%, P<0.001), of Asian ethnicity (12.1% vs. 5.7%, P=0.002) and operated for spondylolisthesis (58.9% vs. 46.2%, P<0.001). Operative parameters stratified by sex are shown in Table 2. Male patients underwent minimally invasive surgery significantly more often than females (31.2% vs 25.5%, respectively; P=0.041) and less frequently had pedicle screws inserted (95.4% vs 98%, respectively; P=0.019).
TABLE 1.
Baseline Patient Characteristics Stratified by Sex
| Sex, n (%) | ||||
|---|---|---|---|---|
| Parameter | Overall (n=1115), n (%) | Male (n=455) | Female (n=660) | P |
| Age, mean±SD (yr) | 60.80±12.45 | 59.2±12.8 | 61.9±12.1 | <0.001 |
| Smoking status | <0.001 | |||
| Active smoker | 306 (27.4) | 148 (32.5) | 158 (23.9) | |
| Ceased smoking | 192 (17.2) | 101 (22.2) | 91 (13.8) | |
| Never smoked | 607 (54.4) | 202 (44.4) | 405 (61.4) | |
| No. missing | 10 (0.9) | 4 (0.9) | 6 (0.9) | |
| Opioid analgesic use | 364 (32.6) | 152 (33.4) | 212 (32.1) | 0.863 |
| No. missing | 102 (9.1) | 37 (8.1) | 65 (9.8) | |
| Bronchial asthma | 63 (5.7) | 22 (4.8) | 41 (6.2) | 0.351 |
| No. missing | 101 (9.1) | 36 (7.9) | 65 (9.8) | |
| BMI, mean±SD (kg/m2) | 26.58±4.61 | 25.8±3.0 | 25.1±3.7 | 0.228 |
| Race/ethnicity | 0.002 | |||
| Caucasian | 861 (77.2) | 375 (82.4) | 486 (73.6) | |
| Black | 30 (2.7) | 14 (3.1) | 16 (2.4) | |
| Asian | 106 (9.5) | 26 (5.7) | 80 (12.1) | |
| Others | 16 (1.4) | 5 (1.1) | 11 (1.6) | |
| No. missing | 102 (9.1) | 35 (7.7) | 67 (10.2) | |
| Prior thoracolumbar surgery | 257 (23.0) | 112 (24.6) | 145 (22.0) | 0.175 |
| No. missing | 100 (9.0) | 51 (11.2) | 49 (7.4) | |
| Indication | <0.001 | |||
| LDH | 202 (18.1) | 92 (20.2) | 110 (16.7) | |
| Lumbar spinal stenosis | 618 (55.4) | 243 (53.4) | 375 (56.8) | |
| Spondylolisthesis | 599 (53.7) | 210 (46.2) | 389 (58.9) | |
| Radiculopathy | 323 (29.0) | 130 (28.6) | 193 (29.2) | |
| No. missing | 101 (9.1) | 36 (7.9) | 65 (9.8) | |
| Discogenic CLBP/DDD | 457 (41.0) | 200 (44.0) | 257 (38.9) | |
| Pseudarthrosis | 56 (5.0) | 28 (6.2) | 28 (4.2) | |
| No. missing | 100 (9.0) | 35 (7.7) | 65 (9.8) | |
| FBSS | 47 (4.2) | 20 (4.4) | 27 (4.1) | |
| No. missing | 100 (9.0) | 35 (7.7) | 65 (9.8) | |
| ASA class | 0.367 | |||
| Class I/II | 791 (70.9) | 330 (72.5) | 461 (69.8) | |
| Class III/IV | 324 (29.1) | 125 (27.5) | 199 (30.2) | |
| No. missing | 17 (1.5) | 7 (1.5) | 10 (1.5) | |
Statistical significance (P < 0.05) values are in bold.
ASA indicates American Society of Anesthesiologists; BMI, body mass index; CLBP, chronic low back pain; DDD, degenerative disc disease; FBSS, failed back surgery syndrome; LDH lumbar disc herniation.
TABLE 2.
Operative Parameters Stratified by Sex
| Sex, n (%) | ||||
|---|---|---|---|---|
| Parameter | Overall (n=1115), n (%) | Male (n=455) | Female (n=660) | P |
| Surgical index level | 0.711 | |||
| T12-L1 | 39 (3.5) | 14 (3.1) | 25 (3.8) | |
| L1-L2 | 24 (2.2) | 8 (1.8) | 10 (1.5) | |
| L2-L3 | 126 (11.3) | 34 (7.5) | 47 (7.1) | |
| L3-L4 | 305 (27.4) | 74 (16.3) | 130 (19.7) | |
| L4-L5 | 657 (58.9) | 179 (39.3) | 280 (42.4) | |
| L5-S1 | 401 (36.0) | 88 (19.3) | 114 (17.3) | |
| No. missing | 100 (9.0) | 46 (10.1) | 54 (8.2) | |
| Surgical technique | 0.842 | |||
| TLIF | 373 (33.5) | 153 (33.6) | 220 (33.3) | |
| PLIF | 449 (40.3) | 192 (42.2) | 257 (38.9) | |
| ALIF | 7 (0.6) | 4 (0.9) | 3 (0.5) | |
| Lateral | 73 (6.5) | 30 (6.6) | 43 (6.5) | |
| No. missing | 213 (19.1) | 76 (16.7) | 137 (20.8) | |
| Minimally invasive surgery | 310 (27.8) | 142 (31.2) | 168 (25.5) | 0.041 |
| Pedicle screw insertion | 1081 (97.0) | 434 (95.4) | 647 (98.0) | 0.019 |
Statistical significance (P < 0.05) values are in bold.
ALIF indicates anterior lumbar interbody fusion; PLIF, posterior lumbar interbody fusion; TLIF, transforaminal lumbar interbody fusion.
Absolute Outcome Measures
Absolute and relative patient-reported outcome measures are shown in Table 3. Female patients presented with significantly higher functional impairment at baseline in terms of ODI (51.5±17.2 vs. 47.8±17.9, P<0.001), as well as pain in terms of NRS back (6.96±2.32 vs. 6.60±2.30, P=0.010) and leg pain scores (6.49±2.76 vs. 6.01±2.76, P=0.005; Fig. 1). At 12 months follow-up, female patients still reported significantly higher ODI (22.76±16.97 vs. 20.50±16.10, P=0.025), but not higher NRS back (3.13±2.38 vs. 3.00±2.40, P=0.355) or leg pain scores (2.62±2.55 vs. 2.34±2.43, P=0.060) compared with male patients.
TABLE 3.
Absolute and Relative Patient-Reported Outcome Measures Stratified by Sex
| Sex | ||||
|---|---|---|---|---|
| Parameter | Overall (n=1115) | Male (n=455) | Female (n=660) | P |
| Absolute score | ||||
| ODI | ||||
| Baseline | 50.20±17.54 | 47.8±17.9 | 51.5±17.2 | <0.001 |
| 12 months | 21.84±16.65 | 20.50±16.10 | 22.76±16.97 | 0.025 |
| NRS back pain | ||||
| Baseline | 6.81±2.32 | 6.60±2.30 | 6.96±2.32 | 0.010 |
| 12 months | 3.08±2.39 | 3.00±2.40 | 3.13±2.38 | 0.355 |
| NRS leg pain | ||||
| Baseline | 6.29±2.32 | 6.01±2.76 | 6.49±2.76 | 0.005 |
| 12 months | 2.51±2.50 | 2.34±2.43 | 2.62±2.55 | 0.060 |
| Change score | ||||
| ODI | -28.12±20.83 | -27.34±20.92 | -28.65±20.77 | 0.315 |
| NRS back pain | -3.72±2.81 | -3.59±2.88 | -3.82±2.76 | 0.197 |
| NRS leg pain | -3.78±3.29 | -3.69±3.46 | -3.85±3.16 | 0.439 |
| MCID | ||||
| ODI | 811 (76.8) | 330 (77.5) | 481(76.3) | 0.729 |
| No. missing | 60 (5.4) | 29 (6.4) | 31 (4.7) | |
| NRS back pain | 836 (76.3) | 336 (75.0) | 500 (77.2) | 0.451 |
| No. missing | 19 (1.7) | 7 (1.5) | 12 (1.8) | |
| NRS leg pain | 807 (74.0) | 332 (74.4) | 475 (73.8) | 0.855 |
| No. missing | 25 (2.2) | 9 (2.0) | 16 (2.4) | |
Statistical significance (P < 0.05) values are in bold.
Values are provided as absolute numbers (%) and mean±SD.
MCID indicates minimally clinical important difference; NRS, numeric rating scale; ODI, Oswestry disability index.
Figure 1.
Graphic representation of ODI, NRS back pain, and NRS leg pain. Error bars represent 95% CI. NRS indicates numeric rating scale; ODI, Oswestry disability index.
Relative Outcome Measures
The change scores at 12 months were not significantly different among male and female patients in terms of ODI (∆1.31, 95% CI: -3.88 to 1.25, P=0.315), NRS back (∆0.22, 95% CI: -0.57 to 0.12, P=0.197), and leg pain (∆0.16, 95% CI: -0.56 to 0.24, P=0.439). Achievement of MCID at 12 months did not differ significantly between sexes for functional impairment [481 (76.3%) vs. 330 (77.5%), P=0.729], or for back pain severity [500 (77.2%) vs. 336 (75.0%), P=0.451], or for leg pain severity [475 (73.8%) vs. 332 (74.4%), P=0.855].
Multivariable Logistic Regression Analyses
Detailed results of the multivariable logistic regression analyses for MCID achievement for ODI, NRS leg, and back pain are displayed in Table 4.
TABLE 4.
Multivariable Logistic Regression Models With MCID Achievement for Pain Measured by ODI, NRS Back Pain, and NRS Leg Pain as Dependent Variables
| ODI MCID | NRS back pain MCID | NRS leg pain MCID | ||||
|---|---|---|---|---|---|---|
| Variable | OR (95% CI) | P | OR (95% CI) | P | OR (95% CI) | P |
| Sex | ||||||
| Male | 1 | 1 | 1 | |||
| Female | 1.020 (0.734–1.414) | 0.903 | 1.339 (0.979–1.830) | 0.067 | 0.852 (0.626–1.155) | 0.305 |
| Age | 0.995 (0.982–1.008) | 0.453 | 0.996 (0.983–1.009) | 0.525 | 0.985 (0.973–0.998) | 0.022 |
| Smoking status | ||||||
| Active smoker | 1 | 1 | 1 | |||
| Ceased smoking | 1.880 (1.150–3.140) | 0.013 | 1.524 (0.937–2.520) | 0.094 | 1.344 (0.872–2.087) | 0.184 |
| Never smoked | 1.345 (0.924–1.954) | 0.106 | 0.856 (0.592–1.228) | 0.402 | 1.362 (0.956–1.937) | 0.086 |
| Ethnicity | ||||||
| Caucasian | 1 | 1 | 1 | |||
| Black | 1.001 (0.417–2.787) | 0.998 | 1.764 (0.662–6.115) | 0.305 | 3.906 (1.140–24.51) | 0.067 |
| Asian | 0.573 (0.360–0.921) | 0.020 | 0.935 (0.580–1.543) | 0.788 | 1.501 (0.878–2.690) | 0.153 |
| Others | 0.570 (0.199–1.866) | 0.315 | 0.375 (0.135–1.080) | 0.059 | 0.174 (0.058–0.483) | 0.001 |
| Minimally invasive surgery | ||||||
| no | 1 | 1 | 1 | |||
| yes | 1.743 (1.175–2.637) | 0.007 | 1.331 (0.936–1.912) | 0.116 | 0.643 (0.466–0.889) | 0.007 |
| Pedicle screw insertion | ||||||
| no | 1 | 1 | 1 | |||
| yes | 0.245 (0.039–0.832) | 0.057 | 0.461 (0.134–1.212) | 0.157 | 2.078 (0.992–4.293) | 0.049 |
Statistical significance (P < 0.05) values are in bold.
CLBP indicates chronic low back pain; DDD, degenerative disc disease; FBSS, failed back surgery syndrome; LDH, lumbar disc herniation; NRS, numeric rating scale; ODI, Oswestry disability index; OR, odds ratio.
Ceased smoking (OR: 1.880, 95% CI: 1.150–3.140, P=0.013), Asian ethnicity (OR: 0.563, 95% CI: 0.360–0.921, P=0.020), and minimally invasive surgery (OR: 1.743, 95% CI: 1.175–2.637, P=0.007) were identified as independent predictors of achievement of MCID for ODI. Female sex was not associated with MCID achievement measured by ODI (OR: 1.020, 95% CI: 0.734–1.414, P=0.903), NRS back pain (OR: 1.339, 95% CI: 0.979–1.830, P=0.067), or NRS leg pain (OR: 0.852, 95% CI: 0.626–1.155, P=0.305).
DISCUSSION
Clarifying the relationship between sex and postoperative outcome after surgical treatment of LDD could help guide clinical decision-making process, identify patients who are risk of unfavorable postoperative outcome and enable more individualized patient care.
Several studies report female sex to be associated with an inferior preoperative clinical status,4 postoperative outcome in terms of more impaired quality of life,20 more surgery-related complications,11 less chances to return to work21 and an overall higher likelihood of reaching an unsatisfactory outcome.22 The reasons for this observed discrepancy remain unclear but may be manifold:23 as indicated by a previous study by Katz et al.24, female patients tend to get operated at a more advanced stage of the disease. In an analysis of over 250,000 patients with LDD from a US national inpatient sample, Al Jammal et al.11 concluded that female patients had 20% reduced odds of receiving surgery compared with male patients. Similarly, Taylor et al.25 found that sex and ethnicity influenced the preoperative workup and surgical management of patients with LDD. While females were more likely to receive imaging tests, they were 52% less likely to have surgery offered.25 This observation suggests an effect of sex-specific bias in clinical decision-making but may also be due to patient preference, as females have been previously shown to be less inclined to take surgical risks.26 As a consequence, various studies previously reported female sex to be associated with an inferior clinical status at presentation,4,20,27,28 which is further supported by the higher preoperative ODI, NRS back, and leg pain scores of female patients in our study.
The underlying anatomic and physiological causality between sex and pain perception have been explored in numerous clinical and laboratory studies.3,29 However, the results have not produced a clear and consistent pattern.3 Whereas some authors reported no sex differences with regard to pain perception,3 the majority of studies concluded that healthy females and female patients with LDD had decreased heat and pressure pain thresholds, an increased radicular pain perception and were more likely to verbalize pain compared with men.30–32 These findings are supported by human and animal studies that showed an association between estrogen receptor polymorphisms and the perception of back pain in female patients with LDD.33,34 Psychosocial factors may also contribute to pain perception, although there is no clear evidence showing a higher rate of depression in female patients with radiculopathy.35 As the reason for the sex-specific differences at presentation are still not entirely understood, future studies should aim to clarify the underlying reasons for the worse preoperative pain and disability status of female patients at baseline.
Analyzing 1115 patients from a multinational, multicenter data set of the FUSE-ML15 cohort, our study identified that female patients experienced a higher absolute degree of functional impairment preoperatively and postoperatively although they experienced a similar relative improvement in functional impairment (change scores, MCID achievement) from surgery compared with male patients. Similarly, preoperative pain scores appeared higher for female patients, although 12-month absolute scores as well as relative improvement was the same for female and male patients.
Lending support to our results, Ströemquist et al.28 reported the outcomes of 11,237 patients from a prospective registry of the Swedish National Spine Surgical Register and concluded that female patients experienced inferior postoperative clinical status due to higher preoperative functional impairment. Differences in postoperative improvement between the sexes has been inconsistently reported among various studies.10,27,28 Some authors noted a similar or greater improvement in female patients compared with men.12,24,27,36 In our study, the multivariable analysis demonstrated that female sex did not significantly predict the achievement of MCID in terms of ODI, NRS back pain, and NRS leg pain. Siccoli et al.10 analyzed 3279 patients from a single-center prospective registry and reported similar results: female patients reported worse symptoms preoperatively and postoperatively but experienced the same degree of improvement/benefit as male patients. Triebel et al.36 investigated the two-year follow-up of 4780 patients using a multivariable analysis and reported that females had worse preoperative functional status but improved more and had similar postoperative outcomes compared with men. In a retrospective analysis of the preoperative and 12 months postoperative COMI scores of 1518 patients undergoing discectomy for different spinal pathologies, Pochon et al.23 noted that woman experienced the same degree of improvement postoperatively and that gender did not influence the probability of reaching a favorable outcome in the multivariable analysis.
One interesting point that is inconsistently corroborated by the literature24 is the differential sex influence on different dimensions of outcome, particularly for subjective outcome measures. For example, in our study, we found that female patients demonstrated higher preoperative scores for both subjective functional impairment and for pain, but postoperatively, only impairment was still significantly higher than in their male counterparts, whereas pain scores were similar between the sexes. It appears that different dimensions of outcome assessment are differentially influenced by sex.24 In the end, physiological differences among sexes are still poorly understood and diverging disease susceptibility, response to inflammation and analgesia, as well as hormonal and psychological factors may be responsible.3,30,37 In addition, the differential effect of sex differences on various outcome measures can be partially explained by the psychometric properties of questionnaires.10,30 It is conceivable that objective outcome measures, such as the five-repetition sit-to-stand test, may be less prone to such confounders.27,38 For the timed-up-and-go test, it has been shown that it may be an appropriate test to overcome sex bias as there were no differences regarding the presence and degree of ODI measured using age-adjusted and sex-adjusted cutoff values.4
In summary, it is important to recognize that our study along with the vast majority of previously published evidence suggests that female patients benefit from spinal fusion in degenerative disease to the same extent as male patients. In this sense, female sex should not simply be regarded as a predictor for worse outcomes after spine surgery since female patients tend to report higher absolute functional impairment and pain scores for various reasons as outlined above. Rather, our results allow for a more nuanced conclusion: while absolute scores are an adequate measure to quantify the magnitude and severity of functional disability and pain, they may be biased by various influences including sex. Therefore, the use of relative measures of improvement such as 12-month change scores or MCID, adjusted for baseline characteristics, may be preferred when analyzing treatment effects.
Strengths and Limitations
Our study evaluated a large multinational cohort of patients, although some centers collected at least part of the data retrospectively. While the majority of studies in the current literature were restricted to the population of one country, our study evaluated a broader population of a total of 11 international centers and encompassed a variety of indications for spinal fusion surgery. Thus, the data in this study may be more generalizable. On the other side, this aspect also contributed to the heterogeneity of the data in our study, which may complicate drawing conclusions of subpopulations or separate indications based on the results provided herein. Moreover, the follow-up duration in the present study was only 12 months. However, it has been previously suggested that 12-month PROMs allow for appropriate evaluation of clinical outcome after spinal fusion.39,40 Our study was limited in the number of included variables and did not report any data on relevant comorbidities, psychosocial aspects, reoperation, complication rates, return to work, preoperative nonopioid analgesia use, preoperative duration of symptoms, use of steroid injections, use of allied health care providers or other nonsurgeon physician resources (e.g. pain specialists), the impact of mental health status, or operative parameters that related to surgical invasiveness (e.g. estimated blood loss), which may have been potential confounders. Furthermore, we did not account for study design. Several articles demonstrated that considering both sex and gender are crucial to be able to disentangle biological from social determinants of health.41,42 To date, few studies reported treatment outcomes after spinal fusion specifically stratified by gender.2,23,43–45 While sex and gender are two different notions, we did not collect any gender-related variables and investigated only the effect of sex on patient-reported outcomes, which does not allow to draw conclusions about the effect of gender and is a significant limitation of the present study. Future studies should be designed to incorporate such gender-related factors in their data collection.
CONCLUSION
Female patients experienced a similar benefit from surgery in terms of the relative improvement in scores for functional impairment and pain compared with male patients. Although female patients on average reported a higher degree of functional impairment and pain preoperatively, at 12 months only their mean scores for functional impairment remained higher than those of their male counterparts, while absolute pain scores were similar for female and male patients. While absolute scores remain an important measure to quantify the magnitude and severity of functional impairment and pain, our study indicates that relative measures (such as change scores or MCID) should be preferably used to account for baseline symptom severity when evaluating treatment effects.
Key Points
Female patients reported higher functional impairment and pain preoperatively.
Both sexes experienced similar relative improvement in scores for functional impairment and pain.
At 12 months, only mean scores of female patients for functional impairment remained higher than those for their male counterparts, absolute pain scores were similar for female/male patients.
Supplementary Material
ACKNOWLEDGMENTS
The authors thank the patients whose anonymized data were used for this research.
Footnotes
The study was approved by the appropriate national and local authorities at the initiating study site (Medical Research Ethics Committees United, Registration Number: W18.004) and at all participating centers.
The data that support the findings of this study are available from the corresponding author, V.E.S, upon reasonable request.
The authors report no conflicts of interest.
Supplemental Digital Content is available for this article. Direct URL citations are provided in the HTML and PDF versions of this article on the journal's website, www.spinejournal.com.
Contributor Information
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Massimo Miscusi, Email: massimo.miscusi@uniroma1.it.
Andrea Perna, Email: perna.andrea90@gmail.com.
Luca Proietti, Email: luca.proietti@policlinicogemelli.it.
Giorgio Lofrese, Email: giorgio.lofrese@gmail.com.
Michele Dughiero, Email: michele.dughiero@gmail.com.
Francesco Cultrera, Email: francesco.cultrera@auslromagna.it.
Marcello D’Andrea, Email: marcellodan@gmail.com.
Seong B. An, Email: anseongbae@gmail.com.
Yoon Ha, Email: yoonhaucsf@gmail.com.
Aymeric Amelot, Email: aymmed@hotmail.fr.
Jorge B. Cadelo, Email: jorgebedia97@gmail.com.
Jose M. Viñuela-Prieto, Email: jovinuel@ucm.es.
Maria L. Gandía-González, Email: marisagg4@hotmail.com.
Pierre-Pascal Girod, Email: dr.girod@neurospine.at.
Sara Lener, Email: sara.lener@i-med.ac.at.
Nikolaus Kögl, Email: nikolaus.koegl@tirol-kliniken.at.
Anto Abramovic, Email: anto.abramovic@tirol-kliniken.at.
Christoph J. Laux, Email: Christoph.Laux@balgrist.ch.
Mazda Farshad, Email: Mazda.Farshad@balgrist.ch.
Dave O’Riordan, Email: dave.oriordan@kws.ch.
Markus Loibl, Email: markus.loibl@gmail.com.
Fabio Galbusera, Email: Fabio.Galbusera@kws.ch.
Anne F. Mannion, Email: anne@annefmannion.com.
Alba Scerrati, Email: a.scerrati@gmail.com.
Pasquale De Bonis, Email: pasquale.debonis@unife.it.
Granit Molliqaj, Email: granitmolliqaj@gmail.com.
Enrico Tessitore, Email: enrico.tessitore@hcuge.ch.
Marc L. Schröder, Email: mljfschroder@gmail.com.
Martin N. Stienen, Email: mnstienen@gmail.com.
Giovanna Brandi, Email: Giovanna.Brandi@usz.ch.
Luca Regli, Email: Luca.Regli@usz.ch.
Carlo Serra, Email: Carlo.Serra@usz.ch.
Victor E. Staartjes, Email: victoregon.staartjes@usz.ch.
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