Low vitamin D levels affect outcomes of orthopedic spinal surgery: An observational study in clinical practice

Abstract

BACKGROUND:

Low vitamin D is a major risk factor for osteoporotic fractures. Evidence also suggests correlation between deficiency and musculoskeletal pain.

OBJECTIVE:

Non-interventional study in patients undergoing spine surgery to investigate links between vitamin D levels and clinical features.

METHODS:

25-OH vitamin D levels were assessed in two cohorts: Cohort 1 (vertebral fractures; VF) and Cohort 2 (other spinal issues; excluding VF). Lab values as well as painDETECT questionnaires, VAS and Oswestry Disability Index (ODI) were recorded. Follow-up visits were conducted a few days and 6 weeks postoperatively.

RESULTS:

One hundred and nine patients were enrolled. Mean VAS measured 72 mm in Cohort 1 and 55 mm in Cohort 2. Mean vitamin D concentrations were 16.8 $\pm$ 11 ng/ml in Cohort 1 and 18.3 $\pm$ 11 ng/ml in Cohort 2. VAS and ODI significantly correlated with vitamin D levels. Median painDETECT scores were 9 in Cohort 1 and 16 in Cohort 2. Six weeks postoperatively mean VAS was 31.4 $\pm$ 28 mm in Cohort 1 and 23.3 $\pm$ 21 mm in Cohort 2. Median painDETECT scores were 5 in both cohorts.

CONCLUSION:

Interactions are apparent between neuropathic pain and vitamin D serum levels. Consequently, vitamin D should be monitored in all patients requiring spinal surgery.

Keywords

Vitamin D level vertebral fracture neuropathic pain osteoporosis musculoskeletal pain

1. Introduction

Human vitamin D intake may be through cholecalciferol as a product of sunlight-dependent synthesis in the skin or dietary through ergocalciferol or cholecalciferol mainly contained in foods of animal origin like dairy products, eggs or various fishes. Vitamin D helps to control calcium absorption in the small intestine. Vitamin D and parathyroid hormone (PTH) interact to mediate skeletal mineralization and maintain stable blood calcium concentrations. Vitamin D has also been shown to have immunomodulatory properties and is known to influence the release of pro-inflammatory mediators, which has helped to shed light on interactions between deficiency and disease [1, 2]. In 2014 DVO (German Osteology Association) guidelines stated that a 25-OH vitamin D (calcidiol) serum concentration below 20 ng/ml (50 nmol/l) is associated with a moderately increased risk (1.5–2-fold) of non-vertebral fractures [3]. Since a correlation between fracture incidence and serum 25-(OH) vitamin D levels in the 10–20 ng/ml range has not been conclusively established, a vitamin D deficiency should not be considered a directly additive, independent prognostic factor for bone fractures.

According to the results of recent studies [3], adult serum levels of

•
10 ng/ml or below are associated with a serious risk of osteomalacia
•
20 ng/ml or below constitute a relevant deficiency in vitamin D
•
30 ng/ml or below constitute a relative deficiency in vitamin D
•
30–60 ng/ml indicate a physiologically safe vitamin D supply
•
above 88 ng/ml indicate excessive amounts of vitamin D and
•
above 150 ng/ml indicate vitamin D overdose

An extensive Germany study [4] showed that an average of 58% of women and 57% of men exhibit low vitamin D levels. These were subject to seasonal fluctuation, averaging 22 ng/ml in summer and 13 ng/ml in winter. A global study of vitamin D levels documented low vitamin D concentrations ( $<$ 20 ng/ml) in 28% of postmenopausal women with osteoporosis [5].

The prevalence of postmenopausal women with serum vitamin D concentrations below 20 ng/ml in southern and central Europe is 40% [6]. Serum vitamin D concentrations below 30 ng/ml were measured in 97% of women with a history of fractures or falls; 72% even exhibited vitamin D levels below 20 ng/ml [7].

Low vitamin D levels are also an important risk factor for osteoporosis. Evaluation of an extensive data review demonstrated that supplementation of vitamin D (700 IU daily) combined with calcium was associated with documented prevention of bone mass depletion [8]. There was also evidence of a direct correlation between vitamin D deficiency and musculoskeletal pain. Consecutive six-month vitamin D supplementation was associated with increased muscle strength and a substantial reduction in back pain [9]. It has also been shown that restoration of physiological vitamin D levels through supplementation in patients with back pain may eliminate symptoms and produce a substantial improvement in quality of life [10]. Scandinavian studies stated that a daily vitamin D dose of 2000 IU should be prescribed for chronic pain patients. Data suggested that chronic back pain patients have excessively low serum vitamin D concentrations and may benefit from supplementation [11, 12].

A non-interventional observational study to enable analysis of the correlations between vitamin D levels and clinical manifestations was designed for systematic investigation of the situation in patients admitted to hospital for elective spinal surgery.

Aim of the present study was to prove a positive correlation between low levels of vitamin D and the incidence of vertebral fractures.
2. Materials and methods

The study was approved by the local ethics committee and conducted in accordance with the Declaration of Helsinki. The study protocol is registered at http://clinicaltrials.gov under registration number NCT01551901.

This non-interventional, open-label, observational study of vitamin D levels was performed including patients presenting for elective spinal surgery due to a history of back pain. To ensure a broad epidemiological coverup there were no extended specific in- or exclusion criteria. All patients presenting for index surgeries were eligible. Patients were enrolled in the study only after their written informed consent. All data obtained for documentation, assessment and publication in this study were pseudonymized.

Samples for 25-OH vitamin D assays were taken from the blood drawn for routine lab tests in the department’s clinical algorithm. No other diagnostic or therapeutic measures were taken beyond those required for routine medical care in these cases. However, all patients participating in this study received general advice to ensure a regular intake of vitamin D. Supplementation was prescribed for patients with a proven vitamin D deficiency upon lab test ( $<$ 20 ng/l). All findings and lab values were recorded in case report forms. Entries were additionally made in painDETECT questionnaires, questionnaires for assessment of pain in other body regions and an Oswestry Disability Index (ODI) form [21].

Surgical procedures were selected in line with good clinical practice based on the diagnoses established on the strength of clinical features and evidence from imaging procedures (plain radiography, CT and MRI). Patients were divided in two cohorts after inclusion: Cohort 1 (vertebral fractures) and cohort 2 (all other spinal issues requiring surgery).

Cohort 1 (VF) received radiofrequency kyphoplasty [22]. Cohort 2 (non-VF) underwent standard surgical procedures like nucleotomy, decompression and/or spondylodesis.

Follow-up took place during the first few days after surgery, at 6 weeks and again at 6 months. The variables investigated at baseline were repeated at the follow-up visits.

Primary endpoint of the study was a comparison of serum concentrations of 25-OH vitamin D pre- and postoperatively. Another objective was to establish the extent of interdependence between the final scores in the painDETECT questionnaire [20] and the corresponding serum vitamin D concentrations, while distinguishing between neuropathic and non-neuropathic pain.

Secondary objectives were to discover whether supplementation advice resulted in an improvement in vitamin D supply during the follow-up period and whether any correlations could be observed in these patients between the baseline situation and subsequent postoperative abnormalities in specific variables.

All datasets were transferred into the BiAS biostatistics analysis package (version 11.02, programmed by H. Ackermann, Frankfurt, Germany). The following formula packages were used: calculation of means, standard deviation and 95% confidence interval for parametric data; calculation of medians, lower, middle and upper quartiles, minimum and maximum for non-parametric data; Welsh’s t-test for cohort comparisons with parametric data and heterogeneous variances. Calculations were also performed using Cohen’s d effect size with pooled variance ( $d=$ 0.2: small, $d=$ 0.5: medium, $d\geqslant$ 0.8: large effect size), the Mann-Whitney U test for cohort comparisons with non-parametric data, and Rosenthal’s d effect size ( $r=$ 0.1: small, $r=$ 0.3: medium, $r\geqslant$ 0.5: large). Wilcoxon’s matched pairs test was used for non-parametric paired cohorts. In addition, the Hodges-Lehmann estimator was used to estimate differences. Contingency tables were calculated using the Mantel-Haenszel chi square statistic. Spearman’s rank correlation coefficient was used to analyze correlations. Level of significance was set at $p=$ 0.05 for all statistical analyses.

3. Results

3.1 Epidemiologic data

Table 1
Prevalence of diagnoses

Diagnoses	n (%)
Vertebral fracture	40 (37%)
Herniated disk	39 (36%)
Spondylolithesis	9 (8%)
Osteochondrosis	9 (8%)
Nerve compression, constriction, spinal instability	12 (11%)

One hundred and nine patients presenting to the Department of Orthopedic and Trauma Surgery of the University Hospital Bonn with low back pain or other back pain issues were included in the study. The following diagnoses (Table 1) were recorded based on the results of clinical examination and assessment of imaging procedures.

Distribution to both observational cohorts was

•

Cohort 1: patients with vertebral fractures (VF: $n=$ 40; 37%)

•

Cohort 2: patients with spinal abnormalities excluding vertebral fractures (non-VF: $n=$ 69; 63%).

Cohort 1: female: $n=$ 37 (93%), male: $n=$ 3 (7%); Cohort 2: female: $n=$ 34 (49%), male: $n=$ 35 (51%). A mean age difference of 15.3 years was ascertained: Cohort 1: 70.2 $\pm$ 11; 95% CI: 67.2–73.9 years; Cohort 2: 54.9 $\pm$ 15; 95% CI: 50.6–60.0 years; $P<$ 0.00001.

Fifteen patients in Cohort 1 had a history of falls, while only 4 patients in Cohort 2 mentioned a fall that preceded their problem. The reported duration of back pain was 10 $\pm$ 16 weeks in Cohort 1 and 37 $\pm$ 52 weeks in Cohort 2 ( $p=$ 0.0002). Back pain distribution by location is summarized in Table 2.

Table 2

Back pain distribution by location

Location	Cohort 1	Cohort 2
	n (%)	n (%)
Cervical	7 (17%)	44 (70%)
Thoracic	21 (53%)	8 (13%)
Lumbal	8 (20%)	1 (1%)
Sacral	1 (2%)	1 (1%)
Cervical $+$ thoracic	3 (8%)	9 (15%)
Thoracic $+$ lumbar	40 (100%)	63 (100%)

3.2 Baseline results

Assessment of pain intensity (VAS 0–100 mm) at the time of admission disclosed an inter-cohort difference of 17 mm ( $p=$ 0.002), with VAS scores of 72.0 $\pm$ 22 mm (95% CI: 65.1–79.0) in Cohort 1 and 55.0 $\pm$ 33 mm (95% CI: 46.9–63.0) in Cohort 2.

A comparison of median ODI detected no difference between the two diagnostic cohorts: ODI (median; quartiles 1 and 3): Cohort 1: 54 (Q1–Q3: 42–66), Cohort 2: 55.5 (Q1–Q3: 40–66). The following means were determined for the primary endpoint, i.e. blood vitamin D concentration (25-OH vitamin D3; ng/ml) depending on diagnostic cohort: Cohort 1: 16.8 $\pm$ 11 (95% CI: 13.1–20.4), Cohort 2: 18.3 $\pm$ 11 (95% CI: 15.6–21.0). The mean difference was 1.5 ng/ml ( $p=$ 0.5).

A breakdown based on cutoff values revealed the following:

•
Deficiency $<$ 20 ng/ml: $n=$ 69 (65%)
•
Insufficiency $<$ 30 ng/ml: $n=$ 20 (19%)
•
Recommended $>$ 30 ng/ml: $n=$ 17 (17%)

The mean blood vitamin D concentration was 16.8 $\pm$ 12 ng/ml in the female population and 19.5 $\pm$ 10 ng/ml in the male population. The mean difference of 2.6 ng/ml does not constitute a significant difference in vitamin D levels between the genders.

A correlation between patient age (all patients) and all vitamin D levels was not detected ( $p>$ 0.5). However, Cohort 1 patients tended to have slightly higher vitamin D levels with increasing age (correlation coefficient: 0.3, $p=$ 0.06). Blood vitamin D concentrations were not dependent on patient gender (correlation coefficient: 0.11; $p=$ 0.2). Pain intensity (VAS) and disability (Oswestry scores) correlated significantly with vitamin D concentrations (correlation coefficient: $-$ 0.24 and $-$ 0.2; $p=$ 0.02 and $p=$ 0.03, respectively). Pain intensity (VAS) correlated clearly with vitamin D levels in Cohort 2 in particular (correlation coefficient: $-$ 0.34; $p=$ 0.02); low vitamin D concentrations were associated with high VAS scores. No correlation between these two parameters was detected in Cohort 1. A negative correlation between Oswestry score (%) and vitamin D levels was again detected only in Cohort 2 (correlation coefficient: 0.29; $p=$ 0.02); there was no apparent interdependence between the two variables in Cohort 1. VAS scores with specific reference to back pain likewise showed a certain dependence on vitamin D levels (correlation coefficient $-$ 0.2; $p=$ 0.03).

Hemoglobin levels for the entire patient population correlated with vitamin D levels (correlation coefficient: 0.2; $p=$ 0.04), but there were no correlations between the two variables depending on diagnostic group. Blood calcium concentrations did not correlate with blood vitamin D concentrations ( $p=$ 0.1).

The comparisons of the individual symptoms featuring in the painDETECT questionnaires (Fig. 1) reveal clear differences between the cohort of patients with vertebral fractures and those without. The median screening result was 9 for Cohort 1 (minimum: 0 – maximum: 27) and 16 for Cohort 2 (minimum: 3 – maximum: 34). This gives a difference (Hodges-Lehman estimator, HLE) of 7. The effect size of the difference (Rosenthal) is $r=$ 0.48; the difference between the two cohorts is significant ( $p<$ 0.00001). Cohort 2 scores for burning, tingling, lightning pains and numbness were significantly higher than in Cohort 1. The specifications for estimation of neuropathic pain involvement give rise to the figures shown in the comparisons in Table 3.

Table 3
Comparison of scores for the 7 symptoms in the pain DETECT questionnaire

Sum score Cohort 1 Cohort 2

Neuropathic pain component n (%) n (%)

0 negative 1 (2.5%) 0 (0%)

$>$ 0–12 negative 32 (80.0%) 26 (38%)

$>$ 12–18 unclear 5 (12.5%) 20 (29%)

$>$ 18–38 probable $>$ 90% 2 (5.0%) 23 (33%)

$X^{2}=$ 20.6; $p<$ 0.00001.

Based on these figures, involvement of a neuropathic component is highly likely in 33% of cases in Cohort 2, and a neuropathic component may be present in another 29% of cases. Involvement of a neuropathic component is unlikely in more than 80% of cases in Cohort 1, so again, this comparison shows a significant difference. The outcome for the second primary endpoint is that, for the total patient population (not broken down into cohorts), there was a negative correlation between vitamin D concentrations and painDETECT sum scores (correlation coefficient: $-$ 0.21; $p=$ 0.03). A significant correlation was determined for Cohort 2 (correlation coefficient 0.32; $p=$ 0.008) but no interaction was detected between the total scores and vitamin D levels in Cohort 1 patients ( $p=$ 0.2). A more precise breakdown of pain intensities by location is given in the form of comparative assessments in Table 4.

Table 4
Comparison of pain intensities by location at baseline examination (VAS)

Cohort 1 VAS [mm] Cohort 2 VAS [mm]

Pain location Mean $\pm$ SD 95% CI Mean $\pm$ SD 95% CI

Back 64.8 $\pm$ 28 55.8–73.8 56.5 $\pm$ 32 48.6–64.4

Left leg 14.6 $\pm$ 28 5.7–23.4 32.6 $\pm$ 38 23.5–41.7

Left hip 9.0 $\pm$ 21 2.4–15.6 20.0 $\pm$ 32 12.3–27.8

Right leg 8.2 $\pm$ 21 1.9–15.5 37.8 $\pm$ 37 28.8–46.8

Right hip 13.1 $\pm$ 27 4.5–21.6 24.6 $\pm$ 34 16.2–32.9

Significant correlations between VAS scores and vitamin D concentrations in subjects with back pain ( $p=$ 0.04) were detected in Cohort 2.

Assessment of the 10 Oswestry Disability Index sections (ODI; Fig. 2) does not indicate differences in disability between Cohort 1 and Cohort 2 patients. The medians from the percentages calculated for each section differed by only 1 percentage point (Hodges-Lehmann estimator). Thus, there is no evidence of a statistically significant difference.

The final median Oswestry score was 54% in Cohort 1 (min. 18; max. 80) and 54% in Cohort 2 (min 13, max 94).
3.3 Six-week results

Sum score	Cohort 1	Cohort 2
Neuropathic pain component	n (%)	n (%)
0 negative	1 (2.5%)	0 (0%)
$>$ 0–12 negative	32 (80.0%)	26 (38%)
$>$ 12–18 unclear	5 (12.5%)	20 (29%)
$>$ 18–38 probable $>$ 90%	2 (5.0%)	23 (33%)

	Cohort 1 VAS [mm]	Cohort 2 VAS [mm]
Pain location	Mean $\pm$ SD	95% CI	Mean $\pm$ SD	95% CI
Back	64.8 $\pm$ 28	55.8–73.8	56.5 $\pm$ 32	48.6–64.4
Left leg	14.6 $\pm$ 28	5.7–23.4	32.6 $\pm$ 38	23.5–41.7
Left hip	9.0 $\pm$ 21	2.4–15.6	20.0 $\pm$ 32	12.3–27.8
Right leg	8.2 $\pm$ 21	1.9–15.5	37.8 $\pm$ 37	28.8–46.8
Right hip	13.1 $\pm$ 27	4.5–21.6	24.6 $\pm$ 34	16.2–32.9

Patients underwent the following surgical procedures: nucleotomy: $n=$ 41 (38%), RF kyphoplasty: $n=$ 40 (37%), spondylodesis: $n=$ 18 (16%), decompression: $n=$ 7 (6%), repositioning: $n=$ 3 (3%). Twelve patients failed to attend for 6-week follow-up and were classified as dropouts. Fifty percent of Cohort 1 patients and 66% of Cohort 2 patients no longer required analgesic medication at 6 weeks. The response to treatment in Cohort 1 was rated very good by 23 patients (64%) and good by 9 patients (25%). Forty-five percent ( $n=$ 27) of Cohort 2 patients rated response as being very good and 36% said it was good ( $n=$ 22). More than 90% of patients in both cohorts said they would undergo the same treatment again if necessary. Blood vitamin D concentrations were 24.5 $\pm$ 13 ng/ml in Cohort 1 ( $n=$ 30); 95% CI: 19.6–29.4; $\Delta$ : 5.9 ng/ml and 19.4 $\pm$ 11 ng/ml in Cohort 2 ( $n=$ 52); 95% CI 16.2–22.5; $\Delta$ : 0.5. For the total study population, the percentage of patients with vitamin D concentrations below 20 ng/ml decreased by more than 10 percentage points within 6 weeks in response to the supplementation advice. The following mean VAS scores were calculated: Cohort 1: 31.4 $\pm$ 28 (95% CI: 22.8–41.9), Cohort 2: 23.3 $\pm$ 21 (95% CI: 17.9–28.7). The intergroup difference was not significant ( $p=$ 0.09). Median final scores from all painDETECT ratings at 6 weeks were 5 (0–12) in Cohort 1; difference from baseline: HLE $=$ 4; effect size: $r=$ 0.6, and 5 (0–26) in Cohort 2; difference from baseline: HLE $=$ 9; effect size: $r=$ 0.52. The decline in overall scores is significant in both cohorts ( $p<$ 0.00001). The final screening scores regarding the likelihood of a neuropathic pain component are presented in Table 5.

Table 5
Comparison of sum scores for the 7 symptoms in the painDETECT questionnaire 6 weeks postoperatively

Sum score	Cohort 1 n ( %)	Cohort 2 n (%)
0; negative	3 (8%)	6 (10%)
$>$ 0–12; negative	33 (92%)	42 (69%)
$\geqslant$ 12–18; inconclusive		8 (13%)
$>\geqslant$ 18–38; probable		5 (8%)

$p=$ 0.03.

The median total Oswestry score was 34% (0–70) for Cohort 1 and 24% (0–64) for Cohort 2 ( $p=$ 0.06). The differences from baseline were HLE $=$ 20.5; $r=$ 0.5 in Cohort 1; $p<$ 0.00001 and HLE $=$ 25.0; $r=$ 0.5 in Cohort 2; $p<$ 0.00001.

The mean reduction in back pain (VAS) was 30.5 mm in Cohort 1 ( $d=$ 0.85; $p<$ 0.00001) and 34.6 mm ( $d=$ 0.96; $p<$ 0.0001) in Cohort 2. The 11.6 mm difference in VAS scores between the two groups can be termed significant.

The following reductions in VAS scores were observed for the other locations: left leg: Cohort 1: 30%; Cohort 2: 63%, left hip: Cohort 1: 29%; Cohort 2: 48%, right leg: Cohort 1: 50%; Cohort 2: 71%, right hip: Cohort 1: 46%; Cohort 2: 60%.

Correlations with vitamin D concentrations were not established for these variables.

4. Discussion

A large body of evidence has accumulated over the last number of years to show that vitamin D has health benefits far beyond the therapeutic areas originally investigated, such as rickets and osteoporosis prevention. The main effects are regulation of calcium metabolism and prevention of bone loss, and the importance of these effects for patients lies in reducing the risk of falls and the associated fractures. A meta-analysis [23] of several carefully selected studies demonstrated a significant reduction in the risk of falls for follow-up periods of up to 3 years with a pooled adjusted odds ratio of 0.78 (95% CI: 0.64–0.92).

In addition, vitamin D influences neuromuscular and immunological function. Antiinflammatory properties mediated by vitamin D receptors on the involved cells have also been demonstrated. Many genes involved in regulating cell proliferation and cell differentiation are subject to the influence of vitamin D [24, 25, 26, 27].

Serum 25-OH vitamin D concentration has been shown to be the best indicator of vitamin D status, reflecting vitamin D synthesis in the skin and dietary vitamin D intake. The half-life is about 15 hours [28].

Large-scale studies in recent years have repeatedly confirmed based on these serum concentrations that large sections of the population have inadequate vitamin D levels [29]. The results of 25-vitamin D assays in a 2008–2011 study showed mean 25-vitamin D levels in the suboptimal range (below 30 ng/ml) across all age groups [30].

Mortality in the ESTHER study was up to 1.7 times higher in subjects with very low or low vitamin D levels than in those with higher blood vitamin D concentrations [31].

The data from the study presented here confirms these general insights for patients with various back pain problems presenting for orthopedic surgery. The average level in this patient population was 17.7 ng/ml, indicating marked deficiency. There were no relevant age-dependent correlations and serum vitamin D concentrations in women were only slightly lower than those in men. It would have been expected to find lower serum vitamin D concentrations in patients with osteoporotic vertebral fractures than in the reference group, especially given that the first group contained significantly more women, significantly older patients and a higher incidence of falls.

In view of the significant deficiency observed in all subjects, no differences were detected in vitamin D levels that would have been attributable solely to a particular diagnosis or another variable. However, the fact that 69% of VF patients had vitamin D levels below 20 ng/ml and another 11% had vitamin D levels below 30 ng/nl indicates a link between vitamin D deficiency and the incidence of osteoporotic fractures.

The two diagnostic cohorts (VF and non-VF) differed significantly regarding the involvement of neuropathic pain components. A significant correlation between painDETECT sum scores and serum vitamin D concentrations was detected in Cohort 2 (non-VF), which may corroborate previous insights into the correlations between neuropathic pain and vitamin D deficiency [32, 33, 34]. Similarly, patients with herniated disk, spinal compression syndromes and spondylolisthesis were more likely to have referred pain in the hips and legs than patients in the VF cohort. Overall pain intensity (VAS) was substantially higher in the vertebral fracture population, however. The intensive supplementation advice provided to patients resulted in an increase in serum vitamin D concentrations within 6 weeks.

Regardless of age or gender, the possibility of vitamin D deficiency should be considered in patients with chronic back pain, be it due to vertebral fractures or other spinal abnormalities, and serum concentrations should be determined. Supplementation increases vitamin D levels and can help in that manner to reduce the risk for several disorders, not just orthopedic.

Footnotes

Conflict of interest

All authors have no conflicts of interest.

Appendix

Figure 1.

PainDETECT questionnaire.

Figure 1.

continued.

Figure 2.

Oswestry Disability Index questionnaire.

Figure 2.

continued.

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Low vitamin D levels affect outcomes of orthopedic spinal surgery: An observational study in clinical practice

Abstract

BACKGROUND:

OBJECTIVE:

METHODS:

RESULTS:

CONCLUSION:

Keywords

1. Introduction

3. Results

3.1 Epidemiologic data

Table 1 Prevalence of diagnoses

Table 5 Comparison of sum scores for the 7 symptoms in the painDETECT questionnaire 6 weeks postoperatively

Footnotes

Conflict of interest

Appendix

References

Table 1
Prevalence of diagnoses

Table 5
Comparison of sum scores for the 7 symptoms in the painDETECT questionnaire 6 weeks postoperatively