Clinical trial NCT05565456: Intercorporal Bone Graft Measurement Study
Official title: Prospective Hounsfield Unit Measurements of Intercorporal Bone Grafts Remodelling Towards Spinal Fusion
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Spondylolisthesis
Spinal Fusion
Keywords: Bone Density
Bone Remodelling
Tomography, X-Ray Computed
Lead sponsor: Rijnstate Hospital
Sponsor class: OTHER
First posted: 2022-10-04
Enrollment: 30
Sex: ALL
Minimum age (years): 45
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Thirty patients with a symptomatic spondylolisthesis (lytic/degenerative/iatrogenic) who have an indication for single level lumbar interbody fusion (PLIF/TLIF) will be recruited.

Brief 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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Hounsfield Units (HU)
timeFrame: The HU will be assessed in the first week after surgery, at 6 months, at one year and at two years post-surgery.
Secondary outcomes:
measure: Intercorporal fusion
timeFrame: Intercorporal fusion will be assessed in the first week after surgery, at 6 months, at one year and at two years post-surgery.
measure: Visual Analogue Scale (VAS) for back and leg pain.
timeFrame: Back and leg pain will be assessed at baseline, at 6 months, at one year and at two years post-surgery.
measure: Oswestry Low Back Pain Disability Questionnaire (ODI), Dutch version.
timeFrame: The degree of functional disability will be assessed at baseline, at 6 months, at one year and at two years post-surgery.
measure: 36-item Research and Development (RAND-36) Health Survey, Dutch version.
timeFrame: The self-reported quality of life will be assessed at baseline, at 6 months, at one year and at two years post-surgery.
Other outcomes:
Locations:
city: Arnhem
country: Netherlands
facility: Rijnstate Hospital
state: Gelderland
Study officials:
affiliation: Rijnstate ziekenhuis
name: Job LC van Susante, Dr. PhD.
role: PRINCIPAL_INVESTIGATOR
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