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Efficacy of platelet rich plasma for bone union on lateral lumbar interbody fusion surgery using unidirectional porous beta-tricalcium phosphate (LLIF-PRP)

Efficacy of PRP for bone fusion in LLIF

Hara Akira

Sept. 04, 2023

13

Men and women with diseases such as posterior scoliosis, lumbar spinal canal stenosis, and lumbar spondylolisthesis that are indications for lumbar lateral interbody fusion. PRP-bearing artificial bones were placed in the spinal cage in all 13 cases and all 29 intervertebral spaces.

At 8 months postoperatively, No. 3 underwent additional surgery due to surgical site infection, and an episode of cardiac arrest due to pulmonary embolism occurred one postoperative day after the surgery, which led to resuscitation. Therefore, the study was suspended from December 2021.After hearing opinions from outside experts, a causal relationship between pulmonary embolism and PRP was rejected. However, we revised the research protocol and patient information documents, summarized the information on the relationship between adverse events that may occur during surgery and PRP, and added the information to the explanation documents. In addition, to enable smooth implementation of the study in the future, we voluntarily added exclusion criteria for rheumatoid arthritis patients using biologic agents with high perioperative risk, and the study was restarted in March 2022. (The patient enrollment period and the study period were extended by 3 months due to the delay in patient enrollment. ) The final number of patients included in the study was 13, but the study was terminated because it was an exploratory study and deemed sufficient to evaluate trends regarding the efficacy of PRP.

Adverse events that occurred in this study included herniated disc at the nonoperative site, vertebral fracture at the fixed cephalad end, endplate injury, dural and anterior longitudinal ligament injury at the operative site, deep vein thrombosis as a perioperative complication, and implant fracture. These were known adverse events that occur in corrective spinal fusion surgery with or without PRP. The most serious adverse event was the death of patient No. 3 at 8 months postoperatively due to pulmonary embolism, which occurred one day after additional surgery due to wound infection. As mentioned above, the causal relationship between pulmonary embolism and PRP was ruled out by the opinions of outside experts.

The analysis was based on a total of 23 vertebrae in 11 cases, excluding two cases: No. 3 died in the middle of the follow-up period, and No. 13 was completely missed in the follow-up period because CT imaging at 6 months postoperatively was not available due to reoperation. [Primary endpoints] Intervertebral bone fusion rate at 12 months 60.9% (14/23 cages) in the group with PRP, 34.8% (8/23 cages) in the group without PRP, and 47.8% in total. There was no significant difference in the rate of bone fusion with or without PRP. The bone fusion rate was lower than in previous studies (70.9%) and in other studies using artificial bones (around 80%). The following factors were postulated as possible factors: a; The percentage of patients who underwent corrective fusion surgery for adult spinal deformity (posterior scoliosis) increased (28.5% in 4/14 cases in the previous study by Kumagai et al.) b; The number of patients with a history of PSL medications and bone fragility due to underlying diseases such as SLE and RA was higher in this study. [Secondary endpoints] 1. Intervertebral bone fusion rate at 6 months postoperatively 43.4% (10/23 cages) in the group with PRP and 26.1% (6/23 cages) in the group without PRP, for a total of 34.8%. There was no statistically significant difference in bone fusion rate with or without PRP. 2. The intervertebral bone fusion rate based on the contact condition between the cage and the vertebral body endplate We evaluated the intervertebral bony fusion at 12 months after surgery using CT MPR coronal/sagittal images immediately after surgery to determine whether the artificial bone was in contact with the upper and lower vertebral body endplates. The results were 76.2% (16/21 cages) in the good contact group and 24.0% (6/25 cages) in the poor contact group. Statistically, the bone fusion rate was significantly higher in the group with good grounding of the artificial bone and endplate. The bone fusion rates by presence/absence of PRP for each good/poor grounding group were as follows, In the good grounding group, 84.6% (11/13 cages) had PRP, 62.5% (5/8 cages) had no PRP, and in the poor grounding group, 30.0% (3/10 cages) had PRP, and 20.0% (3/15 cages) had no PRP. There was no statistically significant difference in the comparison of grounding status combined with and without PRP. 3. Evaluation of the behavior of artificial bone over time (resorption and bone remodeling) The behavior of the PRP-loaded beta-TCP bone was followed over time, mainly by CT. As in previous studies without PRP, metabolism began in the area in contact with the vertebral endplate, resulting in resorption of the artificial bone and bone formation with continuous osteoconductivity from the endplate. When the number of patients with and without beta-TCP resorption/bone formation was counted, there was no significant difference: 6 months postoperatively: 14/23 cages with PRP, 9/23 cages without PRP, and 12 months postoperatively: 17/23 cages with PRP, 15/23 cages without PRP. However, there was an impression that the PRP-loaded beta-TCP bone resorption and bone formation occurred earlier than those without PRP under good grounding conditions.e performed a quantitative trial evaluation by measuring HU (Hounsfield Unit) values of the area of interest at the site of artificial bone grafting in CT, and suggested the possibility of detecting differences depending on the presence or absence of PRP. Sub-analysis will be conducted in the future. 4. Functional assessment: Clinical score The five severity scores of the JOA BPEQ take values from 0 to 100 points, with higher values indicating better condition. Although there were differences in the transition from case to case, the average values showed an upward trend from preoperative to 6 months postoperatively for all five parameters, confirming the improvement in clinical scores due to surgery. On the other hand, there was a decreasing trend from 6 months to 1 year postoperatively. The VAS also improved from preoperatively to 6 months postoperatively, and while back pain was maintained up to 1 year postoperatively, lower limb pain and numbness tended to flare up slightly. Similar to the JOA BPEQ, the ODI score decreased from preoperative to 6 months postoperative, indicating improvement due to surgery, but there was a slight increase in the score at 1 year postoperatively. The trends in these endpoints suggest the possibility that ADL impairment due to long-range spinal fusion, as represented by the corrective fusion surgery cases, may have influenced the responses, or that the aforementioned postoperative adverse events may have had an impact on the responses.

We performed an exploratory study on the effect of PRP on promoting lateral lumbar interbody fusion by unidirectional porous beta-TCP with PRP made from the patient's peripheral blood. The intervertebral bone fusion rate at 1 year postoperatively was 47.8% in all patients, 60.9% in the group with PRP and 34.8% in the group without PRP. There was no statistically significant difference between the two groups, indicating that the effect of PRP in promoting bone fusion was limited.

Mar. 31, 2024

Undecided (paper in progress)

https://jrct.mhlw.go.jp/latest-detail/jRCTb032200199

Yamazaki Masashi

University of Tsukuba Hospital

2-1-1, Amakubo, Tsukuba,

masashiy@md.tsukuba.ac.jp

Noguchi Hiroshi

University of Tsukuba Hospital

2-1-1, Amakubo, Tsukuba

+81-29-853-5625

noguhiro0164@md.tsukuba.ac.jp

Interventional

non-randomized controlled trial

open(masking not used)

no treatment control

single assignment

treatment purpose

1. Patients who receives lateral lumbar interbody fusion surgery for vertebral fracture, lumbar canal stenosis, lumbar spondylolisthesis, adult spine deformity, and so on
2. Patients who receives lateral lumbar interbody fusion surgery at 1-4 levels
3. Patients over 20 years old
4. Patients with informed concent and understanding for treatment

1. Patients with a history of lumbar surgery, purulent spondylitis, or spinal tumor
2. Patients who received other Investigational new drug within 3 months of participating in this clinical study
3. Patients who have a primary illness that is clearly inferior to bone formation (bone metabolic disease, dialysis, and so on)
4. Patients who have uncontrolled diabetes
5. Patients with anemia (Hb<9.0g/dL)
6. Patients who have disorder of blood coagulation.
7. Patients with rheumatoid arthritis who are using biologics with high risk of perioperative infection.
8. Women who are pregnant or suspected ofbeing pregnant or breastfeeding
9. Patients with metal allergy
10. Patients who needs the legal representative
11. Patients who are judged inappropriate by the responsible doctor for the study

Both

vertebral fracture, lumbar canal stenosis, lumbar spondylolisthesis, adult spine deformity

A lumbar lateral interbody fusion is performed by the spinal cage with unidirectional beta-tricalcium phosphate (beta-TCP) artificial bone impregnating platelet-rich plasma (PRP) prepared from the patient's venous blood

Interbody fusion rate at postoperative 12 months

1. Interbody fusion rate at postoperative 6 months
2. bone remodeling and Absorption of artificial bone
3. Contact between the implanted beta- TCP and both upper and lower vertebral endplate
4. Clinical outcomes
5. back pain (Visual analog scale)

Complete

+81-29-853-3914

Mar. 30, 2022