Intercorporal Bone Graft Measurement Study

Spondylolisthesis Clinical Trial

Official title:

Prospective Hounsfield Unit Measurements of Intercorporal Bone Grafts Remodelling Towards Spinal Fusion

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05565456
• Other study ID #: NL81678.091.22
• Secondary ID: 2022-13716
• Status: Recruiting
• Start date: December 2, 2022
• Est. completion date: November 2025

Study information

• Verified date: April 2024
• Source: Rijnstate Hospital
• Contact: Joey FH Reijmer, Drs.
• Phone: 088 - 005 7744
• Email: JReijmer[@]rijnstate.nl
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Instrumented lumbar fusion surgery is often accompanied by interbody fusion using an autologous bone graft that is supposed to expand and remodel to achieve a rigid and lasting bony construction between two vertebrae. However, there is a dearth of knowledge regarding the process of biological remodelling of intercorporal bone grafts. Also, a valid and reliable assessment of fusion status remains challenging because there is no objective tool available to quantify the bone remodelling process. CT-based Hounsfield Units correlate with Bone Mineral Density and can be used as a proxy to establish trajectories over time to assess changes in bone mineral density from the bone graft.

Description:

Instrumented lumbar spinal fusion is a surgical procedure that is widely being used to treat various spinal diseases such as deformities, spondylolisthesis, spondylolysis, spinal instability, and degenerative disc disease. Lumbar fusion is an effective treatment to stabilize the degenerative segments and promote bony fusion and is often combined with subsequent decompression of neural structures or correction of deformities. To date, various surgical fusion techniques are used, but consensus regarding a superior technique is lacking. Also, the location where a surgeon wants to achieve bony fusion varies. Interbody fusion is performed to fuse the upper endplate of one vertebra and the lower endplate of the adjacent vertebra. An intervertebral cage is often used to retain intervertebral height and stability. After insertion of the cage, autologous decompressive bone is impacted behind the cage. Over time, this non-vital bone graft is expected to remodel towards new vital bone and subsequently to create a sustainable fusion between two adjacent lumbar vertebral bodies. However, in case of resorption of the bone graft or adequate bone remodeling, solid bridging of bone may fail to develop and this may result in a pseudarthrosis or non-union. This clinically important complication occurs in 5% to 35% of patients treated with spinal fusion and can lead to pain and a decrease in functional status. Also, subsequent revision surgery for symptomatic pseudarthrosis occurs in up to 24% of patients after fusion surgery. The gold standard to assess interbody fusion is surgical exploration, but due to unpractical and ethical considerations, monitoring fusion status is mainly limited to radiographic image evaluation. CT-scanning is the most established radiographic method option for this, but when a patient improves clinically, conventional radiographs are used more commonly. An orthopaedic surgeon can use several existing scoring criteria to judge the degree of solid bony bridging based on this radiographic imaging. However, research has shown that the inter-observer agreement and diagnostic accuracy of these scoring criteria is relatively low. Correct diagnosis of lumbar fusion on CT has been reported to be as low as 67-72% and at the cervical level non-unions are missed in 20% of the cases. The problem is that, to date, there is no quantitative and objective tool available to quantify the bone remodeling process and to precisely judge whether vertebrae have fused or not. In fact, there is an overall dearth of knowledge about the biological process of ongoing spinal fusion and its association with the development of back and/or leg pain. In vivo bone remodeling can be monitored by using repeated Bone Mineral Density (BMD) measurements. BMD values are traditionally generated using two-dimensional dual-energy X-ray absorptiometry (DEXA) scans which are hindered by overprojection from the iliac crest and metal artefacts. A more suitable proxy for these measurements is the use of Hounsfield Units (HU). HU can be measured on CT-images and highly correlate with BMD. HU have already been used to determine vertebral bone quality after spine surgery and have several clinical applications, including the ability to predict the stability of orthopaedic implants and to assist in surgical decision-making. However, none of these studies have succeeded in improving diagnostic accuracy in establishing spinal fusion. Quantifying the biological bone remodeling process in the bone graft over time can help to evaluate bone growth or bone resorption. Knowledge of changes in bone mineral density from the bone graft could be very useful supplementary information when doubts about fusion status exist. To date, only two feasibility studies with relatively small sample sizes have reported on the value of HU measurements to evaluate bone graft remodeling after lumbar interbody fusion surgery. In one previous cross-sectional study from Spruit et al., published almost 18 years ago, HU measurements were only performed once in the first year after spinal fusion surgery. As such, no information with regards to the evolution of bone graft HU over time were obtained. Recently the feasibility of HU measurements after lumbar spondylodesis (Reijmer et al, submitted) was explored. The HU measurement procedure that was developed during this study had excellent intraobserver reliability. The individual HU trajectories also suggested bone remodeling was not yet completed between one and two years after surgery. However, limitations of the study were a small sample size, the absence of postoperative CT-images made shortly after surgery and the absence of information about the participants' postoperative back and leg pain. This limited insight into the progression of pain and the process of bone graft remodeling in the first year after surgery. This study will build upon the results of the former study in an effort to further the state of the art in this important field of orthopaedics.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: November 2025
• Est. primary completion date: November 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 45 Years to 80 Years

Eligibility

Inclusion criteria:

• non-responsiveness to non-operative treatment in the six months prior to study enrolment
• fusion indicated for only one segment in the L1 to S1/ilium region
• between the age of 45 and 80.

Exclusion criteria:

• receiving revision spine surgery
• not wanting to provide informed consent
• pregnant or expecting to be pregnant within in the next two years.

Related Conditions & MeSH terms

• Spinal Fusion
• Spondylolisthesis

Locations

Country	Name	City	State
Netherlands	Rijnstate Hospital	Arnhem	Gelderland

Sponsors (1)

Lead Sponsor	Collaborator
Rijnstate Hospital

Country where clinical trial is conducted

Netherlands, 

References & Publications (23)

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Bridwell KH, Lenke LG, McEnery KW, Baldus C, Blanke K. Anterior fresh frozen structural allografts in the thoracic and lumbar spine. Do they work if combined with posterior fusion and instrumentation in adult patients with kyphosis or anterior column defects? Spine (Phila Pa 1976). 1995 Jun 15;20(12):1410-8. — View Citation

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Cole CD, McCall TD, Schmidt MH, Dailey AT. Comparison of low back fusion techniques: transforaminal lumbar interbody fusion (TLIF) or posterior lumbar interbody fusion (PLIF) approaches. Curr Rev Musculoskelet Med. 2009 Jun;2(2):118-26. doi: 10.1007/s12178-009-9053-8. Epub 2009 Apr 29. — View Citation

Demir O, Oksuz E, Deniz FE, Demir O. Assessing the effects of lumbar posterior stabilization and fusion to vertebral bone density in stabilized and adjacent segments by using Hounsfield unit. J Spine Surg. 2017 Dec;3(4):548-553. doi: 10.21037/jss.2017.09.05. — View Citation

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Lee S, Chung CK, Oh SH, Park SB. Correlation between Bone Mineral Density Measured by Dual-Energy X-Ray Absorptiometry and Hounsfield Units Measured by Diagnostic CT in Lumbar Spine. J Korean Neurosurg Soc. 2013 Nov;54(5):384-9. doi: 10.3340/jkns.2013.54.5.384. Epub 2013 Nov 30. — View Citation

Martin BI, Mirza SK, Comstock BA, Gray DT, Kreuter W, Deyo RA. Reoperation rates following lumbar spine surgery and the influence of spinal fusion procedures. Spine (Phila Pa 1976). 2007 Feb 1;32(3):382-7. doi: 10.1097/01.brs.0000254104.55716.46. — View Citation

Mobbs RJ, Phan K, Malham G, Seex K, Rao PJ. Lumbar interbody fusion: techniques, indications and comparison of interbody fusion options including PLIF, TLIF, MI-TLIF, OLIF/ATP, LLIF and ALIF. J Spine Surg. 2015 Dec;1(1):2-18. doi: 10.3978/j.issn.2414-469X.2015.10.05. — View Citation

Nguyen HS, Shabani S, Patel M, Maiman D. Posterolateral lumbar fusion: Relationship between computed tomography Hounsfield units and symptomatic pseudoarthrosis. Surg Neurol Int. 2015 Nov 25;6(Suppl 24):S611-4. doi: 10.4103/2152-7806.170443. eCollection 2015. — View Citation

Reijmer JFH, de Jong LD, Kruyt MC, van Gorp MJ, Susante JLC. Repeated CT-based Hounsfield Unit Measurements as a Proxy Measure of Intercorporal Bone Graft Remodeling Towards Spinal Fusion; a Feasibility Study. [Submitted].

Sakeb N, Ahsan K. Comparison of the early results of transforaminal lumbar interbody fusion and posterior lumbar interbody fusion in symptomatic lumbar instability. Indian J Orthop. 2013 May;47(3):255-63. doi: 10.4103/0019-5413.111484. — View Citation

Schreiber JJ, Anderson PA, Hsu WK. Use of computed tomography for assessing bone mineral density. Neurosurg Focus. 2014;37(1):E4. doi: 10.3171/2014.5.FOCUS1483. — View Citation

Schreiber JJ, Anderson PA, Rosas HG, Buchholz AL, Au AG. Hounsfield units for assessing bone mineral density and strength: a tool for osteoporosis management. J Bone Joint Surg Am. 2011 Jun 1;93(11):1057-63. doi: 10.2106/JBJS.J.00160. — View Citation

Schreiber JJ, Hughes AP, Taher F, Girardi FP. An association can be found between hounsfield units and success of lumbar spine fusion. HSS J. 2014 Feb;10(1):25-9. doi: 10.1007/s11420-013-9367-3. Epub 2013 Nov 1. — View Citation

Soriano Sanchez JA, Soriano Solis S, Soto Garcia ME, Soriano Solis HA, Torres BYA, Romero Rangel JAI. Radiological diagnostic accuracy study comparing Lenke, Bridwell, BSF, and CT-HU fusion grading scales for minimally invasive lumbar interbody fusion spine surgery and its correlation to clinical outcome. Medicine (Baltimore). 2020 May 22;99(21):e19979. doi: 10.1097/MD.0000000000019979. — View Citation

Spruit M, Meijers H, Obradov M, Anderson PG. CT density measurement of bone graft within an intervertebral lumbar cage: increase of hounsfield units as an indicator for increasing bone mineral content. J Spinal Disord Tech. 2004 Jun;17(3):232-5. doi: 10.1097/00024720-200406000-00011. — View Citation

van Bilsen MWT, Ullrich C, Ferraris L, Hempfing A, Hitzl W, Mayer M, Koller H. Diagnostic accuracy of CT scan-based criteria compared with surgical exploration for the analysis of cervical fusion and nonunion. J Neurosurg Spine. 2020 Mar 6:1-7. doi: 10.3171/2019.12.SPINE191011. Online ahead of print. — View Citation

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* Note: There are 23 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Hounsfield Units (HU)	The participants' individual and group (mean, SD) HU values of their intercorporal bone graft(s) will be calculated from their (four) CT-scans.	The HU will be assessed in the first week after surgery, at 6 months, at one year and at two years post-surgery.
Secondary	Intercorporal fusion	Intercorporal fusion will be assessed using the 5-point intercorporal fusion criteria by Brantigan et al.	Intercorporal fusion will be assessed in the first week after surgery, at 6 months, at one year and at two years post-surgery.
Secondary	Visual Analogue Scale (VAS) for back and leg pain.	Back and leg pain will be assessed using a (100mm) Visual Analogue Scale (VAS). A higher score indicates more pain.	Back and leg pain will be assessed at baseline, at 6 months, at one year and at two years post-surgery.
Secondary	Oswestry Low Back Pain Disability Questionnaire (ODI), Dutch version.	The degree of functional disability will be assessed using the Dutch version of the Oswestry Low Back Pain Disability Questionnaire (ODI). Scores range from 0-50. A higher score (percentage) indicates a higher degree of functional disability.	The degree of functional disability will be assessed at baseline, at 6 months, at one year and at two years post-surgery.
Secondary	36-item Research and Development (RAND-36) Health Survey, Dutch version.	The self-reported quality of life will be assessed using the Dutch version of the 36-item Research and Development (RAND-36) Health Survey. Scores range depending on the calculation method used. Higher scores indicate better self-reported quality of life.	The self-reported quality of life will be assessed at baseline, at 6 months, at one year and at two years post-surgery.