Congress of Neurological Surgeons Systematic Review and Evidence-based Guidelines for Perioperative Spine: Preoperative Osteoporosis Assessment
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Sponsored by: Congress of Neurological Surgeons (CNS) and the Section on Disorders of the Spine and Peripheral Nerves
Endorsement: Reviewed for evidence-based integrity and endorsed by the American Association of Neurological Surgeons (AANS) and Congress of Neurological Surgeons (CNS)
Authors:
John Dimar, MD1, Erica F. Bisson, MD, MPH2, Sanjay Dhall, MD3, James S. Harrop, MD4, Daniel J. Hoh, MD5, Basma Mohamed, MBChB6, Marjorie C. Wang, MD, MPH7, Praveen V. Mummaneni, MD, MBA3
Departmental and institutional affiliations:
1. Department of Orthopedics, University of Louisville, Pediatric Orthopedics, Norton Children’s Hospital, Norton Leatherman Spine Center, Louisville, KY, USA
2. Clinical Neurosciences Center, University of Utah Health, Salt Lake City, UT, USA
3. Department of Neurosurgery, University of California San Francisco, San Francisco, CA, USA
4. Department of Neurological Surgery and Department of Orthopedic Surgery, Thomas Jefferson University, Division of Spine and Peripheral Nerve Surgery, Delaware Valley SCI Center, Philadelphia, PA, USA
5. Department of Neurosurgery, University of Florida College of Medicine, Gainesville, FL, USA
6. Department of Anesthesiology, University of Florida College of Medicine, Gainesville, FL, USA
7. Department of Neurosurgery, Medical College of Wisconsin, Wauwatosa, WI, USA
Corresponding Author contact information:
John Dimar, MD
Clinical Professor
University of Louisville Department of Orthopedics
Chief of Pediatric Orthopedics Norton Childrens Hospital
Norton Leatherman Spine Center
210 E Gray St
Suite 900
Louisville, KY 40202
(502) 584-7525
jdimar2@aol.com
Keywords: osteoporosis, vitamin D3, calcium, teriparatides, bisphosphonates, denosamab, bone mineral density
Abbreviations:
BMD: bone mineral density
CT: computed tomography
UE: upper extremity
HU: Hounsfield units
PJK: proximal junctional kyphosis
PJF: proximal junctional failure
PS: pedicle screw
PLIF: posterolateral lumbar interbody fusion
PLF: posterolateral spinal fusion
ABSTRACT
Background: Osteoporosis is a metabolic bone disease that commonly affects the elderly. Degenerative spinal disease that may require surgical intervention is also prevalent in this susceptible population. If undiagnosed or untreated before spine surgery, osteoporosis may result in an increased risk of postoperative adverse events. Nontreatment of osteoporosis preoperatively may be related to a poor understanding of bone physiology, a lack of standardized treatment algorithms, limited cost-effective interventions, and reluctance by spine surgeons to be the primary provider of osteoporosis management.
Objective: The objective of this evidence-based review is to develop guidelines for the preoperative assessment and treatment of osteoporosis in patients undergoing spine surgery.
Methods: A systematic review of the literature was performed using the National Library of Medicine/PubMed database and Embase for studies relevant to preoperative diagnostic studies that predict increased risk of osteoporosis-related postoperative adverse events and if the preoperative treatment of low bone mineral density (BMD) in patients with osteoporosis improves outcome.
Results: Seventeen of 281 studies met the inclusion criteria and were included for systematic review. The task force affirmed a Grade B recommendation that preoperative osteoporosis testing with a dual-energy X-ray absorptiometry (DEXA) scan (T score <−2.5), a computed tomography (CT) scan (Hounsfield units [HU] <97.9), and serum vitamin D3 level (<20 ng/mL) predict an increased risk of osteoporosis-related adverse events after spine surgery. The task force determined a Grade B recommendation that preoperative osteoporosis treatment with teriparatide increases BMD, induces earlier and more robust fusion, and may improve select patient outcomes. There is insufficient evidence regarding preoperative treatment with bisphosphonates alone and postoperative outcome.
Conclusion: This evidence-based clinical guideline provides a recommendation that patients with suspected osteoporosis undergo preoperative assessment and be appropriately counseled about the risk of postoperative adverse events if osteoporosis is confirmed. In addition, preoperative optimization of BMD with select treatments improves certain patient outcomes.
RECOMMENDATIONS
Question:
1. What preoperative diagnostic studies predict the risk of osteoporosis-related adverse events after spine surgery?
Recommendations:
Preoperative testing with a DEXA scan T score <−2.5, a CT scan (Hounsfield Units <97.9), or serum vitamin D3 level <20 ng/mL is associated with poor bone mineral density and predicts an increased risk of a postoperative adverse event in individuals undergoing spinal instrumentation. Preoperative assessment with one of these tests (DEXA scan, CT, or serum vitamin D3 level) should be performed in patients with suspected osteoporosis. Patients with confirmed osteoporosis should be counseled regarding the potential increased risk of postoperative adverse events.
Strength of Recommendation: Grade B
Question:
2. Does preoperative treatment of low bone mineral density decrease risk of postoperative adverse event after spine surgery?
Recommendations:
Clinicians should consider preoperative teriparatide in patients with osteoporosis undergoing spinal instrumentation to decrease risk of postoperative adverse events, including screw loosening and a delayed or lower rate of fusion.
Strength of Recommendation: Grade B
There is insufficient evidence to support the use of bisphosphonates alone in patients with osteoporosis undergoing spinal instrumentation to decrease postoperative adverse events after spinal instrumentation.
Strength of Recommendation: Grade Insufficient
INTRODUCTION
Goals and Rationale
This clinical guideline has been created to improve patient care by outlining the appropriate information gathering and decision-making processes involved in the treatment of patients with preoperative osteoporosis; specifically, if preoperative identification and treatment of this metabolic bone disorder decreases risk of postoperative adverse events after spine surgery. Spinal surgical care is provided in many different settings by many different providers. This guideline has been created as an educational tool to guide qualified physicians through a series of diagnostic and treatment decisions in an effort to improve the quality and efficiency of care.
This guideline should not be construed as including all proper methods of care or excluding methods of care reasonably directed to obtaining the same results. The ultimate judgment regarding any specific procedure or treatment must be made in light of all circumstances presented by the patient and the needs and resources particular to the locality or institution.
Osteoporotic fragility fractures have become a major health care epidemic with the aging population, occurring in 2.1 million patients yearly.1 The spine is affected in 245,000 patients annually, and mortality after a vertebral fracture is 22.4%, 32.7%, and 49.4% at 1, 2, and 4 years, respectively.2 Suboptimal diagnosis and management of bone health before spine surgery can contribute to increased osteoporosis-related postoperative adverse events and unsatisfactory surgical outcomes in the elderly. These include pseudarthrosis, instrumentation complications (particularly loss of fixation at the screw–bone interface), and proximal junctional failure (PJF), with potentially catastrophic spinal fracture with or without neurologic injury.3 The cause of these postoperative complications may be multifactorial; however, poor bone density is often a major contributor that is potentially modifiable with appropriate preoperative diagnosis and management.
Osteoporosis can result from aging, genetic and environmental factors, certain comorbidities, and abnormal homeostasis of calcium and vitamin D metabolism. Despite the relative prevalence of osteoporosis and vitamin D3 deficiency4,5 and various available diagnostic6 and treatment modalities, there is a lack of consensus regarding the management of osteoporosis before spine surgery.7 This deficiency may be related to poor understanding by many spine surgeons of bone physiology, limited cost-effective interventions, and the reluctance of spine surgeons to be the primary provider of treatment or to consult an endocrinologist. The objective of this evidence-based review is to develop guidelines for the preoperative assessment and treatment of osteoporosis in patients who are undergoing spine surgery.
Methods
The guidelines task force initiated a systematic review of the literature and evidence-based guideline relevant to the preoperative treatment of patients with spinal disorders with osteoporosis. Through objective evaluation of the evidence and transparency in the process of making recommendations, this evidence-based clinical practice guideline was developed for the diagnosis and treatment of adult patients with various spinal conditions. These guidelines are developed for educational purposes to assist practitioners in their clinical decision-making processes. Additional information about the methods used in this systematic review is provided below.
Literature Search
The task force members identified search terms/parameters and a medical librarian implemented the literature search, consistent with the literature search protocol (see Supplemental Digital Content 1), using the National Library of Medicine/PubMed database and Embase for the period from 1946 to September 20, 2019, using the search strategies provided in Supplemental Digital Content 1.
Inclusion/Exclusion Criteria
Articles were retrieved and included only if they met specific inclusion/exclusion criteria (Supplemental Digital Content 2). These criteria were also applied to articles provided by guideline task force members who supplemented the electronic database searches with articles from their own files. To reduce bias, these criteria were specified before conducting the literature searches.
Rating Quality of Diagnostic Evidence
The guideline task force used a modified version of the North American Spine Society’s (NASS) evidence-based guideline development methodology. The NASS methodology uses standardized levels of evidence (Supplemental Digital Content 3) and grades of recommendation (Supplemental Digital Content 4) to assist practitioners in easily understanding the strength of the evidence and recommendations within the guidelines. The levels of evidence range from Level I (high quality randomized controlled trial) to Level IV (case series). Grades of recommendation indicate the strength of the recommendations made in the guideline based on the quality of the literature. Levels of evidence have specific criteria and are assigned to studies before developing recommendations. Recommendations are then graded based upon the level of evidence. To better understand how levels of evidence inform the grades of recommendation and the standard nomenclature used within the recommendations, see Supplemental Digital Content 4.
Guideline recommendations were written using a standard language that indicates the strength of the recommendation. “A” recommendations indicate a test or intervention is 2 “recommended”; “B” recommendations “suggest” a test or intervention and “C” recommendations indicate a test or intervention or “is an option.” “I” or “Insufficient Evidence” statements clearly indicate that “there is insufficient evidence to make a recommendation for or against” a test or intervention. Task force consensus statements clearly state that “in the absence of reliable evidence, it is the task force’s opinion that” a test or intervention may be appropriate.
In evaluating studies as to levels of evidence for this guideline, the study design was interpreted as establishing only a potential level of evidence. As an example, a therapeutic study designed as a randomized controlled trial would be considered a potential Level I study. The study would then be further analyzed as to how well the study design was implemented and significant shortcomings in the execution of the study would be used to downgrade the levels of evidence for the study’s conclusions (see Supplemental Digital Content 4 for additional information and criteria).
Revision Plans
In accordance with the Institute of Medicine’s standards for developing clinical practice guidelines, the task force will monitor related publications after the release of this document and will revise the entire document and/or specific sections “if new evidence shows that a recommended intervention causes previously unknown substantial harm; that a new intervention is significantly superior to a previously recommended intervention from an efficacy or harms perspective; or that a recommendation can be applied to new populations.”8 In addition, the task force will confirm within 5 years from the date of publication that the content reflects current clinical practice and the available technologies for the evaluation and treatment for patients with perioperative spinal disease.
RESULTS
The initial literature search encompassed terms relevant to all chapters in this guideline series and yielded 6812 abstracts (5689 after duplicates were deleted). After a double-blind review, the literature review search yielded 281 abstracts for this question. Task force members reviewed all abstracts distilled from the literature search and identified the relevant literature for full text review and extraction in accordance with the Literature Search Protocol that addressed the two clinical PICO (patient/population, intervention, comparison, and outcomes) questions (Supplemental Digital Content 5). Two members of the task force initially screened all the abstracts culled from the literature followed by all members of the entire task force who graded the best research articles that answered the two research questions. The task force graded the articles from Level I through Level IV. The Task force reviewed 281 articles, collected data on 78, and finally selected 17 articles for use in developing the chapter guidelines (Supplemental Digital Content 6).
DISCUSSION
Question
1. What preoperative diagnostic studies predict risk of osteoporosis-related adverse events after spine surgery?
Recommendations
Preoperative testing with a DEXA scan T score <−2.5, a CT scan (Hounsfield Units <97.9), or serum vitamin D3 level <20 ng/mL is associated with poor bone mineral density and predicts an increased risk of a postoperative adverse event in individuals undergoing spinal instrumentation. Preoperative assessment with one of these tests (DEXA scan, CT, or serum vitamin D3 level) should be performed in patients with suspected osteoporosis. Patients with confirmed osteoporosis should be counseled regarding the potential increased risk of postoperative adverse events.
Strength of Recommendation: Grade B
There were 11 articles that specifically addressed this question and met the inclusion and exclusion criteria. These studies primarily evaluated the predictive effect of preoperative serum vitamin D3 levels (1 study) on time to fusion and nonunion and CT and DEXA scan (10 studies) on cage subsidence, pedicle screw loosening, proximal junctional kyphosis (PJK), and outcome measures. There were no level I studies. There were 4 level II studies and 7 level III studies. There were no level IV studies included in the recommendation.
Level II Evidence
There is significant Level II evidence the relationship of osteoporosis to adverse events after spinal fusion surgery. Cho et al9 retrospectively reviewed a 2-year series of 268 patients who underwent posterolateral fusion (PLF=182 patients) or one level posterior interbody fusion (PLIF=86 patients) to evaluate the effect of osteoporosis on patient related outcomes, fusion success, instrumentation failure, and cage subsidence. Two groups were evaluated based on their T scores: group A (non-osteoporotic: T score > -1.0 consisting of 55 patients and group B (osteoporotic: T-score < -2.5 consisting of 31 patients). The authors found that low BMI was associated with both cage subsidence (65.4% vs. 17.6%, P < 0.001) and screw loosening rates (32.3% vs.12.7%, P < 0.029). Other than osteoporosis, the groups had similar demographics except that group A had a higher average BMI, and group B had an expected higher rate of osteoporosis treatment of 48% vs. 4% (p<0.001). Although patient-related clinical outcomes did not differ between the osteoporotic patients (group B) who had cage subsidence or screw loosening and the normal BMD patients (group A), the fusion rate was lower in those that had screw loosening compared with those that did not (71.4% vs 93.9%, P = .038). The authors suggest that surgeons should continue to monitor screw loosening to detect a potential nonunion.
Sakai et al10 retrospectively evaluated the mean value of the HUs inside a rectangle within the pedicle, which was defined as the HU of screw trajectory. The authors used a CT scanning model superimposing preoperative images on the postoperative CT using 3-dimensional image analysis software. They found that the mean HU values of the screw trajectory were significantly less in the osteoporotic patient group compared with the nonosteoporotic group (147 ± 94 vs 208 ± 91, P < .001). The osteoporotic group was associated with increased screw loosening and was particularly a risk factor in women. The authors recommended additional augmentation with cement, hooks, or lamina taping in females with low bone density to prevent pedicle screw loosening.10 Yagi et al11 performed a retrospective propensity-matched study with 2 years postoperative follow-up of patients with preoperative DEXA scans. Two cohorts were compared: a moderate osteoporosis group (M group; T >−1.5) versus a severe osteoporosis group (S group: T <–1.5). They observed that BMD was a risk factor for PJF, and the incidence of PJF was significantly higher in the severe group (33% vs 8%, odds ratio [OR] 6.4 [95% confidence interval {CI} 1.2-32.3], P < .01). They concluded that surgeons should consider prophylactic measures against PJF when correcting adult spinal deformity in patients with low BMD.
One study included for review was not supportive of the effect of osteoporosis on spine surgery’s adverse events. Yagi et al12 in an earlier article reviewing patients with adult spinal deformity found no correlation between DEXA scan T scores of the hip and spine, and curve magnitude, fusion, and complication rates.
Level III Evidence
Ravindra et al13 retrospectively reviewed a series of prospectively enrolled patients to evaluate the relationship between vitamin D3 deficiency (<20 ng/mL) and fusion rate. They found that nonunion at 12 months was associated with vitamin D deficiency (20% of patients with adequate serum vitamin D3 level vs 38% of vitamin D3–deficient patients, P = .063). In addition, multivariate analysis showed that vitamin D3 deficiency was an independent predictor of nonunion (OR 3.449, P = .045) when adjusted for age, sex, obesity, fusion length, location, graft type, smoking, and bone morphogenetic protein use. Finally, when the authors analyzed the vitamin D3–deficient group (<20 ng/mL) versus the insufficient group (20-30 ng/mL) versus the nondeficient group (>20 ng/mL), there was a significantly longer estimated median time to fusion in the vitamin D3–deficient group (12 vs 8.6 vs 6 months, P = .001). They concluded that serum vitamin D3 levels may affect nonunion rate and time to fusion.13
Schreiber et al14 retrospectively reviewed postoperative CT scans at a minimum of 12 months measuring the HUs and found that the successful fusion levels had higher CT HUs than nonunion levels. The authors reported that successful lumbar fusion was associated with higher bone density both globally and within the fusion construct levels compared with patients with CT evidence of nonunion.14 Kim et al15 showed in a retrospectively reviewed consecutive series that patients with osteoporosis trended toward increased posterior spinous process fractures after an interspinous process device placement. There was a trend toward lower BMD in the fractures group as measured by DEXA and CT HU scans, but the association was weak.15 Oh et al16 performed a retrospective review of PLIF and found that BMD had a significant but weak correlation with cage subsidence (r = 0.285, P < .001). Severe osteoporotic segments (T score <−3.0) had greater risk of severe subsidence (>3 mm), but that subsidence did not cause a deterioration in clinical outcomes.16 Kim et al17 retrospectively reviewed a prospectively collected database of 364 patients after adult deformity surgery with 2 years’ postoperative follow-up. All patients underwent preoperative DEXA scans and osteoporosis was defined as a T score <−2.5. Osteoporosis was present in 20.4% of patients who ultimately developed PJK versus only 9.8% of patients who did not develop PJK (P = .016). This observation suggests that a T score <−2.5 is associated with higher likelihood of PJK in patients undergoing adult deformity surgery.17 Puvansearajah et al18 performed a multivariate analysis of patients with 5 years of postoperative follow-up and found that osteoporosis increases the risk of revision surgery (OR 1.98 [95% CI 1.60-2.46], P < .0001). More than one third (44.9%) of patients undergoing revision surgery had osteoporosis. Finally, Salzmann et al19 retrospectively evaluated 21 patients who had long segment spinal fusion surgery (mean 5.6 levels) that included the sacrum and found a weak association between BMD as measured by a standard
qualitative CT scan of the L1/L2 vertebral body. They unexpectedly found no association between sacral fractures and BMD. The study did find, however, that obese patients had a 52.4% (11/21) incidence of sacral fractures (P = .002)(Univariant Analysis Showed the OR 5.99, P = .030).19
Question
2. Does preoperative treatment of low bone mineral density decrease risk of postoperative adverse event after spine surgery?
Recommendations
Clinicians should consider preoperative teriparatide in patients with osteoporosis who are undergoing spinal instrumentation to decrease the risk of postoperative adverse events, including screw loosening and delayed or lower rate of fusion.
Strength of Recommendation: Grade B
There is insufficient evidence to support the use of bisphosphonates alone in patients with osteoporosis undergoing spinal instrumentation to decrease postoperative adverse events after spinal instrumentation.
Strength of Recommendation: Grade Insufficient
There were 6 articles that specifically addressed this question and met inclusion and exclusion criteria. The task force identified 3 Level II studies, 2 Level III studies, and 1 Level IV study.
Level II Evidence
Ohtori et al20 performed a prospective, nonrandomized sequential study of osteoporotic postmenopausal females with equal BMD undergoing instrumented decompression and fusion (local autograft) for symptomatic degenerative spondylolisthesis. There were 57 females divided into 2 groups: the first 28 patients received a weekly dose of a bisphosphonate (risedronate). The next 29 patients received daily teriparatide injections. All patients were followed for 1 year and evaluated with CT scanning preoperatively and at 3, 6, and 12 months postoperatively for fusion. The rate of bone fusion in the teriparatide group was significantly higher (82% fusion rate at 8 months) than that in the risedronate group (68% fusion rate at 10 months; P < .05). The teriparatide group also demonstrated earlier fusion. Although teriparatide was superior to bisphosphonate regarding fusion rate and time to fusion, both groups had similar clinical outcomes.20 Ohtori et al21 evaluated 62 patients divided into 3 groups: 22 patients received no osteoporotic treatment (control), 20 received a bisphosphonate (risedronate), and 20 received teriparatide. They demonstrated that the incidence of pedicle screw loosening was significantly lower in the teriparatide group (7%) compared with the bisphosphonate (risedronate) group (13%), which was similar to the control group (15%; P < .05) Teriparatide was also associated with increased bone mass compared with bisphosphonate.21
Cho et al22 evaluated a prospective cohort of 47 patients undergoing PLIF with pedicle screws that were divided into 2 groups: the first group (23 patients) received daily teriparatide injections for 3 months which was alternated with a bisphosphonate for 3 months; the second group (24 patients) received oral bisphosphonate. Both groups underwent their respective osteoporosis treatment protocol for 1 year postoperatively. In addition to clinical outcome, postoperative T scores (DEXA scan), fusion rate, and duration to fusion (CT) were assessed. The cyclical teriparatide plus bisphosphonate group showed a significantly higher fusion rate at 6 months after surgery versus the bisphosphonate alone group (77.8% vs 53.6 %), while fusion rates were equal at 2 years postoperatively (92.6% vs 96.4%). CT follow-up at 12 months postoperatively demonstrated bridging bone in 88.9% of the bisphosphonate group and 87.5% of the teriparatide group. Screw loosening was 10.7% in the bisphosphonate group and 11.1% in the teriparatide group. Cage subsidence was 14.3% in the bisphosphonate group and 14.8% in the teriparatide group. None of these CT outcomes were significantly different between the 2 groups (P = .374, P = .648, and P = .626, respectively). There was no significant difference in T score between the 2 groups at 12 and 24 months postoperatively, although the teriparatide group trended toward a higher BMD (DEXA T score −3.0 vs −3.4) and earlier improvement in T scores (0.7 ± 1.4 vs 0.1 ± 0.5, P = .013). There was no significant difference between cohorts with respect to clinical outcomes. There authors concluded that there was no significant benefit in fusion rate and clinical outcome when adding teriparatide with bisphosphonate compared with bisphosphonate alone, but the addition of a teriparatide resulted in faster bony union and a higher BMD recovery rate.22
Level III
Wang et al23 performed a retrospective comparative cohort study of 59 patients undergoing anterior cervical discectomy and fusion. Group A (31 patients) was treated for osteoporosis with calcium, vitamin D, and diphosphonate. Group B received no treatment. All patients underwent DEXA scan with osteoporosis defined as a T score <−2.5 with no baseline difference between groups (P = .584). The authors found that group A (osteoporosis treatment) exhibited significantly better bone mineral density (g/cm2) than group B (no treatment) at 8.3 months postoperatively, as well as improved sagittal alignment (P = .03), interbody disc height (P = .03), and visual analog scale (P = .03) for upper limb pain.23 Kang et al24 retrospectively reviewed 97 postmenopausal women undergoing PLIF and compared 63 patients that were treated with bisphosphonates versus 34 that had no treatment. All subjects had osteoporosis as measured by preoperative DEXA scan (bisphosphonate group, T <−2.7 vs no treatment T <−2.3, P < .001). The authors found that bisphosphonates may negatively delay fusion short term for the first 6 months but not at 2 years postoperatively. Regardless, overall fusion rate in those treated with bisphosphonate was >80% and clinical outcomes were comparable to those who were not treated with bisphosphonate.24
Level IV
Kim et al25 retrospectively evaluated 44 patients undergoing PLIF with osteoporosis diagnosed by CT. Patients were treated either with bisphosphonate (alendronate) versus no bisphosphonate. The fusion rate was similar for the bisphosphonate group (66.7%) versus the no bisphophonate (73.9%; P = 599). Subjects that developed nonunion appeared to have more endplate degeneration compared with those who did not (91.3% vs 52.4%, P = .004). The authors concluded that alendronate does not negatively affect fusion rates in osteoporotic patients.25
Future Research
The lack of level I evidence is an area for improvement that would also benefit future guidelines. Future research should include randomized controlled studies to compare the efficacy of preoperative osteoporosis treatment protocols (single or multiagent), such as vitamin D3, teriparatide, bisphosphonates, and denosumab, in improving bone health and clinical outcome after spine surgery.
Conclusions
Undiagnosed and/or untreated osteoporosis can lead to potentially significant postoperative adverse events in patients undergoing spine surgery. A systematic review of the literature identified that preoperative assessment with DEXA scan (T score <−2.5), CT (HUs < 97.9) and serum vitamin D3 level (<20 ng/mL) predicted a risk of adverse events, including lower fusion rate, instrumentation failure (cage subsidence and screw loosening), and PJF. Preoperative treatment with teriparatide was associated with a higher fusion rate, earlier fusion, and lower screw loosening rates, whereas there was conflicting evidence regarding the potential benefit of preoperative bisphosphonates alone. Spine surgeons should consider preoperative assessment and treatment with these modalities in patients with suspected osteoporosis who are undergoing spine surgery and counsel patients regarding the potential risks when indicated.
Conflicts of Interest
All Guideline Task Force members were required to disclose all potential COIs before beginning work on the guideline, using the COI disclosure form of the AANS/CNS Joint Guidelines Review Committee. The CNS Guidelines Committee and Guideline Task Force Chair reviewed the disclosures and either approved or disapproved the nomination and participation on the task force. The CNS Guidelines Committee and Guideline Task Force Chair may approve nominations of task force members with possible conflicts and restrict the writing, reviewing, and/or voting privileges of that person to topics that are unrelated to the possible COIs. See below for a complete list of disclosures.
Author Disclosure
Marjorie Wang, MD Zimmer Biomet, Medtronic, Abbott, ABNS, AANS, JNS Spine Editorial Board
James Harrop, MD Depuy Sysnthesis, Ethician, Globus, Stryker
Erica Bisson, MD PCORI, NREF, MiRvs, nView, Stryker, Medtronic, MiRvs, nView
Praveen Mumanneni, MD AO Spine, NREF, ISSS, Depuy, Globus, Stryker, Spinicity, ISD Depuy, Thieme Publishers, Springer Publishers, CNS/NPA
John Dimar, MD Medtronic, Depuy, Stryker, Johnson & Johnson, Pfizer, Glaxo-Smith Kline, Eli Lily, Abbot, Hoffman La Roche, Abbie, Pfizer, Norton Hospital, Medtronic, Stryker, SRS & FOSA (2020), JAAOS, Spine, Spinal Deformity, GSJ (Reviewer)
Sanjay Dhall, MD Depuy Synthes, Globus Medical, Great Circle Technologies
Daniel Hoh, MD The Spine Journal Editorial Board, CNS Officer, CNS Foundation Board, JNS Spine Editorial Board, The Spine Journal Editorial Board
Funding
These evidence-based clinical practice guidelines were funded exclusively by the Congress of Neurological Surgeons and the AANS/CNS Joint Section on Disorders of the Spine and Peripheral
Disclaimer of Liability
This clinical, systematic, evidence-based clinical practice guideline was developed by a multi-disciplinary physician volunteer taskforce and is provided as an educational tool based on an assessment of the current scientific and clinical information regarding this guideline topic. These guidelines are disseminated with the understanding that the recommendations by the authors and consultants who have collaborated in their development are not meant to replace the individualized care and treatment advice from a patient's physician(s). If medical advice or assistance is required, the services of a physician should be sought. The proposals contained in these guidelines may not be suitable for use in all circumstances. The choice to implement any particular recommendation contained in these guidelines must be made by a managing physician in light of the situation in each particular patient and on the basis of existing resources.
Acknowledgments
The guidelines task force would like to acknowledge the CNS Guidelines Committee for their contributions throughout the development of the guideline, the AANS/CNS Joint Guidelines Review Committee, the AANS/CNS Joint Section on Disorders of the Spine and Peripheral Nerves for their donation to the CNS Foundation to support this project, as well as the contributions of Kirsten Aquino, contracted project manager for the CNS, Trish Rehring, MPH, Associate Director for Evidence-Based Practice Initiatives for the CNS, Janet Waters, MLS, BSN, RN, for assistance with the literature searches and Kenneth Probst for the cover illustrations. Throughout the review process, the reviewers and authors were blinded from one another. At this time, the guidelines task force would like to acknowledge the following individual peer reviewers for their contributions: Patricia Raksin, MD, Jason Stacy, MD, Neil Majmunder, MD, Yi Lu, MD, Alex Beier, MD, Andrew Carlson, MD, Brandon Rocque, MD, Robert Whitmore, MD, Jay Turner, MD, Owoicho Adogwa, MD
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20. Ohtori S, Inoue G, Orita S, et al. Teriparatide accelerates lumbar posterolateral fusion in women with postmenopausal osteoporosis: prospective study. Spine. 2012;37(23):E1464-1468.
21. Ohtori S, Inoue G, Orita S, et al. Comparison of teriparatide and bisphosphonate treatment to reduce pedicle screw loosening after lumbar spinal fusion surgery in postmenopausal women with osteoporosis from a bone quality perspective. Spine. 2013;38(8):E487-492.
22. Cho PG, Ji GY, Shin DA, Ha Y, Yoon DH, Kim KN. An effect comparison of teriparatide and bisphosphonate on posterior lumbar interbody fusion in patients with osteoporosis: a prospective cohort study and preliminary data. European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society. 2017;26(3):691-697.
23. Wang M, Meng X, Li Y, Feng Y, Chang Z, Hai Y. Effects of anti-osteoporosis treatment in the elderly with anterior cervical discectomy and fusion. Acta orthopaedica et traumatologica turcica. 2016;50(2):186-190.
24. Kang T, Park SY, Hong SH, Lee JH, Lee SH, Park JH. Bone union after spinal fusion surgery using local bone in long-term bisphosphonate users: a prospective comparative study. Archives of osteoporosis. 2019;14(1):74.
25. Kim SM, Rhee W, Ha S, Lim JH, Jang IT. Influence of alendronate and endplate degeneration to single level posterior lumbar spinal interbody fusion. Korean Journal of Spine. 2014;11(4):221-226.
Supplemental Digital Content 1. Literature searches
See Chapter 1: Congress of Neurological Surgeons Systematic Review and Evidence-Based Practice Guidelines for Perioperative Spine: Preoperative Opioid Evaluation for details on full PubMed and EMBASE search terms.
Supplemental Digital Content 2. Inclusion Criteria
Articles that did not meet the following criteria, for the purposes of this evidence-based clinical practice guideline, were excluded. To be included as evidence in the guideline, an article had to be a report of a study that:
• Investigated patients with cervical spine surgery, thoracic spine surgery, and lumbar spine surgery;
• Excluded patients with tumor, trauma, or infections;
• Included patients ≥18 years of age;
• Were studies that enrolled ≥80% of cervical spine surgery, thoracic spine surgery, and lumbar spine surgery (we include studies with mixed patient populations if they report results separately for each group/patient population);
• Was a full article report of a clinical study;
• Was not a medical records review, meeting abstract, historical article, editorial, letter, or commentary;
• Appeared in a peer-reviewed publication or a registry report;
• Enrolled a minimum of 20 patients;
• Was of humans;
• Was published in or after 1946;
• Quantitatively presented results;
• Was not an in vitro study;
• Was not a biomechanical study;
• Was not performed on cadavers;
• Was published in English;
• Was not a systematic review, meta-analysis, or guideline developed by others.
Systematic reviews or meta-analyses conducted by others, or guidelines developed by others were not included as evidence to support this review due to the differences in article inclusion/exclusion criteria specified compared with the criteria specified by the Guidelines Task Force. Although these articles were not included as evidence to support the review, these articles were recalled for full-text review for the Guidelines Task Force to conduct manual searches of the bibliographies.
Supplemental Digital Content 3.
Criteria grading the evidence
The task force used the criteria provided below to identify the strengths and weaknesses of the studies included in this guideline. Studies containing deficiencies were downgraded 1 level (no further downgrading allowed, unless so severe that study had to be excluded). Studies with no deficiencies based on study design and contained clinical information that dramatically altered current medical perceptions of topic were upgraded.
1. Baseline study design (i.e., therapeutic, diagnostic, prognostic) determined to assign initial level of evidence.
2. Therapeutic studies reviewed for following deficiencies:
• Failure to provide a power calculation for a randomized controlled trial (RCT);
• High degree of variance or heterogeneity in patient populations with respect to presenting diagnosis/demographics or treatments applied;
• Less than 80% of patient follow-up;
• Failure to utilize validated outcomes instrument;
• No statistical analysis of results;
• Crossover rate between treatment groups of greater than 20%;
• Inadequate reporting of baseline demographic data;
• Small patient cohorts (relative to observed effects);
• Failure to describe method of randomization;
• Failure to provide flowchart following patients through course of study (RCT);
• Failure to account for patients lost to follow-up;
• Lack of independent post-treatment assessment (e.g., clinical, fusion status, etc.);
• Utilization of inferior control group:
• Historical controls
• Simultaneous application of intervention and control within same patient
• Failure to standardize surgical/intervention technique;
• Inadequate radiographic technique to determine fusion status (e.g., static radiographs for instrumented fusion).
3. Methodology of diagnostic studies reviewed for following deficiencies:
• Failure to determine specificity and sensitivity;
• Failure to determine inter- and intraobserver reliability;
• Failure to provide correlation coefficient in the form of kappa values.
4. Methodology of prognostic studies reviewed for following deficiencies:
• High degree of variance or heterogeneity in patient populations with respect to presenting diagnosis/demographics or treatments applied;
• Failure to appropriately define and assess independent and dependent variables (e.g., failure to use validated outcome measures when available).
Rating evidence quality. Levels of evidence for primary research questiona
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Therapeutic studies: Investigating the results of treatment
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Prognostic studies: Investigating the effect of a patient characteristic on the outcome of disease
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Diagnostic studies: Investigating a diagnostic test
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Economic and decision analyses: Developing an economic or decision model
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Level I
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· High-quality randomized trial with statistically significant difference or no statistically significant difference but narrow confidence intervals
· Systematic reviewb of Level I RCTs (and study results were homogeneousc)
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· High-quality prospective studyd (all patients were enrolled at the same point in their disease with
≥80% follow-up of enrolled patients)
· Systematic reviewb of Level I studies
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· Testing of previously developed diagnostic criteria on consecutive patients (with universally applied reference gold standard)
· Systematic reviewb of Level I studies
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· Sensible costs and alternatives; values obtained from many studies with multiway sensitivity analyses
· Systematic reviewb of Level I studies
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Level II
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· Lesser quality RCT (e.g., <80% follow-up, no blinding, or improper randomization)
· Prospectived comparative studye
· Systematic reviewb of Level II studies or Level I studies with inconsistent results
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· Retrospectivef study
· Untreated control subjects from an RCT
· Lesser quality prospective study (e.g., patients enrolled at different points in their disease or <80% follow-up)
· Systematic reviewb of Level II studies
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· Development of diagnostic criteria on consecutive patients (with universally applied reference criterion standard)
· Systematic reviewb of Level II studies
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· Sensible costs and alternatives; values obtained from limited studies with multiway sensitivity analyses
· Systematic reviewb of Level II studies
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Level III
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· Case control studyg
· Retrospectivef comparative studye
· Systematic reviewb of Level III studies
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· Case control studyg
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· Study of nonconsecutive patients without consistently applied reference criterion standard
· Systematic reviewb of Level III studies
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· Analyses based on limited alternatives and costs and poor estimates
· Systematic reviewb of Level III studies
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Level IV
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Case seriesh
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Case series
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· Case-control study
· Poor reference standard
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· Analyses with no sensitivity analyses
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RCT, randomized controlled trial.
aA complete assessment of quality of individual studies requires critical appraisal of all aspects of the study design.
bA combination of results from ≥2 previous studies.
cStudies provided consistent results.
dStudy was started before the first patient enrolled.
ePatients treated one way (e.g., instrumented arthrodesis) compared with a group of patients treated in another way (e.g., uninstrumented arthrodesis) at the same institution.
fStudy was started after the first patient enrolled.
gPatients identified for the study based on their outcome, called “cases” (e.g., pseudoarthrosis) are compared with those who did not have outcome, called “controls” (e.g., successful fusion).
hPatients treated one way with no comparison group of patients treated in another way.
Supplemental Digital Content 4. Linking levels of evidence to grades of recommendation
| Grade of Recommendation |
Standard Language |
Levels of Evidence |
|
| A |
Recommended |
≥2 consistent Level I studies |
|
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B
|
Suggested
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One Level I study with additional supporting Level II or III studies
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≥2 consistent Level II or III studies
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|
C
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Is an option
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One Level I, II, or III study with supporting Level IV studies
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≥2 consistent Level IV studies
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I (insufficient or conflicting evidence)
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Insufficient evidence to make recommendation for or against
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A single Level I, II, III, or IV study without other supporting evidence
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≥1 study with inconsistent findings*
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*Note that in the presence of multiple consistent studies, and a single outlying, inconsistent study, the grade of recommendation will be based on the level of the consistent studies.
Supplemental Digital Content 5. PRISMA Flowchart
*In addition to duplicate removal, the librarian also removed strictly animal or children/adolescent studies not identified by search strategy and case reports dealing with 1 to 2 persons as encountered.
Supplemental Digital Content 6. Evidence table
|
PICO Question
|
Author, Year
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Type of Evidence
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Study Type
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Level of Evidence
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Reviewer’s Conclusions
|
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1
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Cho et al., 20189
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Therapeutic
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Retrospective comparative
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II
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This study affirms radiographic but negates clinical. Although higher cage subsidence and screw loosening, no difference in clinical outcomes
|
|
1
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Kim et al., 201215
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Therapeutic
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Prospective case control
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III
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This is a prognostic study that was downgraded because of insufficient N for power. In the setting of SP fracture after ISP device placement, there was a trend of lower BMD in fracture vs no fracture patients
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1
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Kim et al., 201317
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Therapeutic
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Retrospective case series
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III
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This study affirms osteoporosis related to PJK and is a retrospective review with no adjusted analysis
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|
1
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Oh et al., 201716
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Therapeutic
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Retrospective comparative case series
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III
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This study affirms the radiographic portion but negates the clinical. Also, indicates radiographic adverse outcomes—cage subsidence but not clinical outcome was impacted by osteoporosis
|
|
1
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Puvanesarajah et al., 201618
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Therapeutic
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Retrospective case series
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III
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Study affirm that osteoporosis is predictive of revision surgery in ASD
|
|
1
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Ravindra et al., 20155
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Diagnostic
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Retrospective comparative
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III
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Study affirms low vitamin D is associated with nonunion. Downgraded because of vitamin D levels assessed within 72 hours of surgery
|
|
1
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Sakai et al., 201810
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Diagnostic
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Retrospective comparative
|
II
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Study finds that BMD and HU of screw trajectory were both associated with screw loosening
|
|
1
|
Salzmann et al., 201919
|
Therapeutic
|
Retrospective comparative
|
III
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Negative study finds that BMI and gender are more important risk factors than BMD for fracture after fusion
|
|
1
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Schreiber et al., 201414
|
Diagnostic
|
Retrospective comparative case control
|
III
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Study affirms that successful lumbar fusion was associated with higher bone density both globally and within the fusion construct levels compared to patients with CT evidence of nonunion
|
|
1
|
Yagi et al., 201112
|
Therapeutic
|
Retrospective comparative
|
II
|
Negative study finds no significant correlation between BMD and fusion or complication
|
|
1
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Yagi et al., 201811
|
Therapeutic
|
Retrospective comparative
|
II
|
Study finds low BMD is a risk factor for PJK
|
|
2
|
Cho et al., 201722
|
Therapeutic
|
Prospective comparative
|
II
|
The study negates the use of teripratide over bisphosphonate. Although no difference in overall fusion rate or clinical outcome, the TP group had faster rate to fusion and more improved BMD scores. Negates = teripratide over bisphosphonate--although no difference in overall fusion rate or clinical outcome, the TP group had faster rate to fusion and more improved BMD scores
|
|
2
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Kang et al., 201924
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Therapeutic
|
Prospective comparative
|
III
|
Long-term BP users have longer time to fusion but no difference in overall fusion rates at 2 years compared with nonusers
|
|
2
|
Kim et al., 201425
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Therapeutic
|
Restrospective comparative
|
IV
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Study concludes alendronate does not impact fusion rates. Downgraded because of unknown patients in each group
|
|
2
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Ohtori et al., 201220
|
Therapeutic
|
Prospective
|
II
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Study concludes that teriparatide had faster healing/bony union rates compared with BP
|
|
2
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Ohtori et al., 201321
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Therapeutic
|
Prospective comparative RCT
|
II
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Study affirms therapeutic teriparatide, finding administration of TP, but not BP, decreased screw loosening in patients with osteoporosis
|
|
2
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Wang et al., 201623
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Therapeutic
|
Restrospective comparative
|
III
|
Study negates for ACDF. Patients with antiosteoporosis treatment had better radiographic parameters at final follow-up as well as for VAS in upper limb
|
ACDF, anterior cervical discectomy and fusion; ASD, adult spinal deformity; BMD, bone mineral density; CT, computed tomography; HU, Hounsfield unit; ISP, interspinous process; PICO, patient/population, intervention, comparison, and outcomes; PJK, proximal junctional kyphosis; RCT, randomized controlled trial; SP, spinous process; TP, teripratide; VAS, visual analog scale