Introduction/background

In 2012, the Danish Finance Act (DFA) devoted 11 million Euros to the development of national clinical guidelines. The Danish Health Authority (DHA) was requested to lead the work of publishing national clinical guidelines on different health areas to support evidence-based decision making and uniform high-quality treatment across Denmark. One of these health areas was lumbar spinal stenosis (LSS) which was chosen due to the large variation in treatment practice in the different regions of Denmark and because of the high burden of disease.

Although the prevalence of LSS is uncertain, it is considered a very common condition among elderly patients. In a study by Ishimoto et al. [1], the authors reported the prevalence of symptomatic LSS to be 10% in a Japanese general population (mean age 66) and increasing with age. In Denmark, nearly 30% of the population will be over the age of 60 in the year 2030 [2] and the burden of disease is therefore expected to further increase.

LSS can cause significant pain and disability leading to dramatically reduced quality of life, immobility, and functional limitation. Also, a recent study by Ammendolia et al. [3] investigated the physical and psychological impact of LSS from patients’ perspectives and found that in addition to pain and limited walking ability, the emotional effects of the disability was impactful to the patients’ lives.

Degenerative LSS is caused by age-related changes in the spine, such as arthrosis of the facet joints, thickening of the ligamentum flavum, and bulging of dehydrated disks. Thereby, the spinal canal is narrowed which may result in symptoms due to neural compression such as radiating pain, numbness and weakness, diminished walking capacity, and balance disturbances. The symptoms are often worsened by standing and walking and relieved by sitting or lying down. When crouching while walking, the symptoms may be diminished [4]. In addition, patients with LSS very often have concurrent back pain although this is not specific for LSS. The diagnosis is based on the presence of these symptoms often obtained from the case history and maybe combined with primarily MRI or with CT if MRI is contraindicated.

Furthermore, standing anterior–posterior and lateral radiographs are sometimes used as a supplement to uncover spinal instability and presurgical planning in patients in whom bony anatomy needs to be illustrated accurately [5].

The treatment of patients suffering from LSS is diverse. Some patients are offered pain medications, some are offered nonsurgical treatment such as exercise and manual treatment, and some are recommended decompression surgery of the neural structures with or without concomitant fusion of the spinal segment.

The purpose of this paper was to summarize the Danish national clinical guideline published in Danish September 2017 [6] for treatment modalities of LSS in patients above 65 years of age. The mandate of the working group was to make recommendations on a maximum of ten interventions covering different treatment options both nonsurgical and surgical, to ensure uniform high-quality treatment of patients with LSS.

Materials and methods

Study design

The clinical guideline was based on a critical systematic review of the scientific literature followed by meta-analyses. The final recommendations were a balance between the evidence available and potential risk of harms together with patient preference. A detailed DHA handbook [7] of the method was followed based on the Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) approach. The full clinical guideline in Danish is available on the webpage of DHA [6].

Description of the work process

A project group of employees from DHA consisting of a chairman, a project manager, a lead reviewer, a search specialist, a methodologist, and a multidisciplinary work group was formed. The work group members were appointed by invitation from professional organizations and scientific societies and were composed of two neurosurgeons, two orthopedic surgeons, one rheumatologist, one anesthesiologist, one geriatrician, one radiologist, one nurse, two physiotherapists, one chiropractor, and one medical practitioner. Potential conflict of interest was published on the DHA homepage [8]. The work group members participated in formulating the ten research questions for evaluation, grading the literature, and formulating the recommendations. A reference group with representatives from the Danish public healthcare system and patient organizations approved the clinical questions and gave advice on the recommendations.

The lead reviewer coordinated the work and drafted the report.

Treatment questions

The work group agreed on ten research questions concerning nonsurgical and surgical treatment of LSS to be considered.

The research questions were structured according to the PICO framework in which the questions are divided into four components (population, intervention, comparison, and outcome) [9].

Population

This study was restricted to patients with LSS verified with relevant radiological examination. Additionally, the target group was characterized by significant symptoms such as radiating pain, numbness, balance disturbances, diminished walking capacity, limited function and loss of activity of daily living, and worsening of the symptoms by standing and walking and relieved in rest.

Patients with other kinds of radiating leg pain such as vascular claudication, hip arthrosis, and disk herniation were excluded. Patient populations with radiological signs of spinal instability were excluded.

Even though LSS can be present in all age groups (although prevalence increases with age), the guideline was targeted on patients above the age of 65 years.

Intervention

The intervention included nonsurgical intervention, medical intervention, and surgical intervention.

Comparison

Nonsurgical intervention was compared to either no treatment or to usual care, which was not specified any further to avoid exclusion of relevant literature. Medical intervention was compared to no treatment or to treatment with non-opioid pain medication. Surgical treatment was compared to no treatment or nonsurgical treatment.

Outcome

For each research question, outcomes measures were determined. Up to four of these were determined to be the primary outcome measures. For most questions leg pain, walking distance, and physical disability were the primary outcomes. In the surgical research questions, surgical complications were included as a primary outcome. Other outcome measures comprised of quality of life, risk of falling, the need for pain medication, and side effects to medication. Outcomes were divided into short-term follow-up defined as 0–12 weeks and long-term follow-up defined as 6–18 months.

Literature review

Search parameters and terms were determined by the multidisciplinary group, and a literature search was completed by a specialist from DHA according to the search protocols. The following electronic databases were searched for English, Scandinavian, and German language publications from 2006 to 2016: Medline, Embase, PsycInfo, CINAHL, and Pedro. The search terms and strategies are available at the DHA website [10].

The literature search was performed in three steps: The first search was performed on clinical guidelines, the second on systematic reviews, and the third on randomized controlled trials. The lead reviewer screened and retrieved the titles and abstracts. Potentially eligible papers were collected in full text and a work group member and the lead reviewer independently screened the papers for inclusion and exclusion criteria. In case of disagreements, the paper was discussed to achieve consensus.

The best research evidence available was used to answer the PICO questions. Clinical guidelines were evaluated according to AGREE, systematic reviews according to AMSTAR, and randomized studies according to Cochrane Risk of Bias Tool.

In case of high-quality clinical guidelines or systematic reviews, data were extracted directly from these studies. Data from clinical randomized studies were extracted by the lead reviewer and a work group member independently. Disagreements on the data extraction were solved by consensus. The handling of references and data extractions was performed by the use of the web-based software Covidence. Data were exported to the RevMan software, and meta-analyses were performed by the methodologist.

The quality of the evidence was graded according to the GRADE definition: very low, low, moderate, or high (Table 1).

Table 1 Definitions of grades of recommendation, assessment, development, and evaluation (GRADE) adapted from Balshem et al. 2011
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Creation of recommendations

The evidence was presented to the work group in tables, and forest plots were presented when meta-analyses were performed. From the available evidence, strong or weak recommendation either for or against a treatment was suggested (Table 2).

Table 2 Recommendations and their definitions by the Danish Health Authority (DHA)
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In lack of evidence, expert opinion reached by discussion in the work group was the basis for practical recommendation.

The final recommendations were based on the evidence available together with potential positive or negative effects as well as patient preference. When the recommendations were established, work group members developed the guideline content, referencing the literature that supported the recommendations.

Results

In total, ten clinical questions were covered. Nonsurgical treatment for LSS was covered by two research questions concerning supervised exercise and manual therapy, while one other question addressed rehabilitation after surgery for LSS. Pharmacological treatment was covered in five questions concerning the use of paracetamol, NSAIDs, opioids, muscle relaxants, and neurogenic pain medication. Two questions covered the surgical treatment concerning decompression and fusion. A summary of the interventions and recommendations is presented in Table 3.

Table 3 PICO questions, recommendations, definitions of interventions, supporting evidence, and comments regarding lumbar spinal stenosis
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None of the PICO questions could be answered by means of existing clinical guidelines or reviews (step one and two in the literature search). The recommendations were therefore based on RCTs for seven of the PICO questions and the remaining three on professional consensus. All RCTs were graded as low or very low quality mostly due to indirectness, small study sample, and imprecision.

Only one RCT was identified comparing supervised exercise as treatment for LSS to patient education and information [11]. The study found no statistical significant differences between the two interventions for any of the outcomes. Due to the general benefits of exercise and patient preference, the final recommendation was in favor of supervised exercise.

One RCT compared manual therapy and muscle strength exercise to flexion exercise and walking training and found no statistical significant differences on outcomes except for the treatment-satisfaction subscale of Zurich Claudication Questionnaire improvement in favor of manual therapy, although the effect size did not reach the predefined criterion for clinical relevance [12]. As there are no known general benefits of manual therapy, the final recommendation was not in favor of manual therapy based on the lack of knowledge in the literature.

Postsurgical supervised exercise was compared to home exercise or no exercise in two RCTs [13, 14]. No differences were found in any of the outcomes, but due to the general benefits of exercise and patient preference, the recommendation favored postsurgical supervised exercise.

Treatment with pain medication for LSS was covered by five PICO questions in which the specific pain medication was compared to no pain medication or to pain medication with non-opioid medication.

No studies concerning nonsteroidal anti-inflammatory drugs (NSAIDs), paracetamol, or muscle relaxants were identified. The final recommendations based on consensus did not favor any of the three pain medications primarily due to the lack of evidence and risk of side effects.

With regard to medication for neurogenic pain, two randomized studies were identified [15, 16]. One study comparing gabapentin to placebo found a statistical significant improvement in leg pain and walking distance in favor of gabapentin, but this was not a consistent finding on all time points, and the effect size did not reach clinical significance. The other study showed no difference between pregabalin and placebo in leg pain, walking distance, and clinical outcomes. Because of this lack of evidence and a significant risk of side effects, the recommendation did not favor neurogenic pain medication.

One RCT was identified in which two different opioids (oxymorphone hydrochloride and propoxyphene/acetominophen) were compared to placebo [17]. The study was terminated early due to serious side effects to propoxyphene/acetominophen. The study showed no statistical significant differences between the three medications in pain and physical function. Because of lack of evidence and the risk of side effects, the recommendation did not favor opioids.

Surgical treatment for LSS was covered by two PICOs: decompression and supplementing decompression with fusion either instrumented or noninstrumented.

Surgical decompression was addressed in three RCTs [18,19,20]. In all studies, decompression was compared to exercise or general advice. All studies showed a large proportion of cross-over particular from the nonsurgical arm to the surgical arm, (43% after 2 years in the study by Weinstein and 57% after 2 years in the study by Delitto). In the study by Weinstein, both intention-to-treat analysis and as-treated analysis were performed, and in the as-treated analysis, the results from a cohort study were included. Overall, the studies showed statistical significant improvement in leg pain and ODI in favor of decompression, but predefined cut-points for clinical significance were not reached. The largest effect was seen when including the as-treated analysis, and the smallest effect was seen in the intention-to-treat analysis. The final recommendation was in favor of surgical decompression due to the statistically significant and partly clinical relevant improvement in leg pain and ODI.

Surgical decompression supplemented with instrumented stabilization was identified in one study by Ghogawala et al. [21]. No studies on noninstrumented stabilization were identified. In the study by Ghogwala et al., patients were randomized to either decompression or decompression supplemented with instrumented stabilization. All patients in this study had been diagnosed with stable spondylolisthesis. The study reported a statistical significant improvement in quality of life measured with SF-36, but not in the ODI. The number of patients needing reoperation was lower in the treatment arm with additional stabilization. The final recommendation did not favor instrumented stabilization on patients with stable spondylolisthesis due to the lack of relevant clinical difference in outcome compared to decompression without stabilization.

Discussion

Patients with significant symptoms due to LSS such as radiating pain, numbness, balance disturbances, diminished walking capacity, low back pain, limited function, and loss of activity of daily living verified with relevant radiological examination might benefit from supervised exercise. As we found, no randomized studies showing significant better outcome in patients receiving supervised exercise compared to usual care; the treatment should focus on general conditioning. Manual therapy may be considered for patients with spinal stenosis in case of concomitant low back pain, but has no clinical effect on neurogenic pain. In addition, manual therapy has no effect on general conditioning.

NSAIDs and paracetamol were the only drugs investigated which may be considered for a short time in case of concomitant low back pain. We found no evidence for the effect of the pharmacological treatment options investigated in this guideline on neurogenic pain. The national clinical guideline ‘Diagnosis and Treatment of Degenerative Lumbar Spinal Stenosis’ from North American Spine Society (2011) [22] also found insufficient evidence to make a recommendation for or against the use of pharmacological treatment for patients with LSS. Guidelines on sciatica (radicular neurogenic pain) from both the National Institute of Health Care Excellence (NICE) in the UK (2016) [23] and Danish National Guidelines (DNG) (2016) [24] recommend against routine use of paracetamol and that NSAIDs is used in the lowest effective dose and only after considering the risk for side effects for the individual patient. Also, they recommend that opioids should not be used routinely. Patients with LSS are older than patients with sciatica considered in the guidelines from NICE and DNG and therefore in higher risk of comorbidity and side effects which should be carefully considered when recommending pharmacological treatment.

Surgical decompression should be considered as the treatment option for symptomatic LSS in case of serious symptoms for longer than 3–6 months. Care should be taken to inform the patients about general possible complications associated with decompression, increased risk due to possible comorbidity, and expected outcome [25]. In case of spinal instability, instrumented or noninstrumented spinal fusion could be considered.

Despite the great number of patients with LSS, there is a lack of RCTs concerning this patient population. There are no or only few studies investigating the effect of medical treatment for LSS, and only few studies explore the effect of nonsurgical treatment. The number of studies concerning surgery for spinal stenosis is slightly bigger, but in these studies, the cross-over from one arm to the other, and especially from the nonsurgical arm to the surgical arm, is found in more than 50%, which tends to diminish the treatment effect of decompression. In the study by Weinstein et al. [20], the as-treated analysis was performed to avoid the cross-over problem, but thereby, the effect of randomization is no longer present. In addition to that, the results were combined with the results from a cohort study, and this is blurring the effect of the randomization even more.

Nevertheless, the RCTs included in this guideline concerning decompression surgery show the largest improvement for patients with symptomatic LSS compared to other treatment modalities. Stabilization procedure does not seem to increase the effect based on very-low quality evidence. However, only patients with stable spondylolisthesis were included in the study by Ghogawala et al., and the results might have been different had the patient population included instable spondylolisthesis. The recommendation against spinal fusion is supported by a high-quality RCT by Försth with two and five years follow-up (not included in this guideline) [26].

The major strength of this guideline was the adherence to the relevant scientific standards, and the work was assisted by expert research librarians and guideline methodologists. Also, the working group was composed of clinicians with a wide range of professional background ensuring a broad forum for discussion which was important due to the lack of evidence. The weakness of this work was the lack of clinical trials in most areas, with the consequence that several of the recommendations were reached by consensus in the working group. Also, the recommendations based on the literature were based on either few or only one clinical trial. Overall, the workgroup found a substantial lack of evidence for the effectiveness of the interventions addressed. Therefore, new high-quality trials are likely to impact the recommendations in future guidelines. However, the GRADE working group encourages to make recommendations even though they are not based on solid evidence [27]. In addition, the guideline only addresses 10 PICO questions and had a national focus which means that other treatment options such as epidural steroid injections were not covered in this guideline.

It is recommended that the guideline is updated three years after publication and that guideline recommendations are implemented in national and regional patient course descriptions for primary and secondary care. Collection of process and effect indicators could be achieved by creating a nationwide, multidisciplinary spinal registry for the primary and secondary care units. To move the field of research forward, high-quality RCTs on all aspects of treatment of LSS are needed including research in defining phenotypes of LSS.

Conclusion

A multidisciplinary work group developed a national clinical guideline for nonsurgical and surgical treatment in patients over 65 years of age with LSS. The recommendations were all based on either weak evidence or professional consensus.

The guideline work group recommends that the management of LSS should include surgical decompression for symptomatic LSS. Supervised exercise and postsurgical supervised exercise are recommended due to the general beneficial effects of training on general health, even though there is no evidence on an effect on neurogenic pain. The guideline recommends against manual therapy, paracetamol, NSAIDs, opioids, neurogenic pain medication, muscle relaxants, and decompression combined with instrumented fusion as there was no evidence of the beneficial effect.

Summary of recommendations

Guideline recommendations by the Danish Health Authority:

1. The management of lumbar spinal stenosis should include surgical decompression for symptomatic lumbar spinal stenosis

2. Decompression combined with instrumented fusion is not indicated as there is no evidence of beneficial effect in the stable spine

3. All actions known to be beneficial on general health like supervised exercise and postsurgical supervised exercise are recommended even though there is no evidence on an effect on neurogenic pain

4. The guideline recommends against manual therapy, paracetamol, NSAIDs, opioids, neurogenic pain medication, muscle relaxants