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Clinical Outcome and Histological Findings After Induced Leakage of PMMA Loaded With Methotrexate and Cisplatin
Alvaro Silva González1,2, Rafael Llombart-Blanco1, Marcela Gallegos Angulo3
1Department of Orthopedic Surgery, University of Navarra, Pamplona, Spain.
Study Design:
Animal experimental model.
Objective:
To study the clinical behavior and histological changes in the spinal cord, nerve roots and perivertebral muscles of the spine after induced leakage of polymethylmethacrylate (PMMA) loaded with antiblastic drugs during vertebroplasty in an animal model of pigs.
Methods:
We performed vertebroplasty on 25 pigs. The animals were divided into 3 groups: vertebroplasty with PMMA alone (control group), vertebroplasty with PMMA loaded with methotrexate (MTX) and vertebroplasty with PMMA loaded with cisplatin (CYS). At 2 vertebral levels, epidural and prevertebral, massive cement leaks were induced. Animals were evaluated daily. Two weeks later, the pigs were sacrificed, and the tissues that came in contact with the cement were analyzed.
Results:
The clinical results for each of the groups were reported. The control group had no clinical alterations. In the MTX group, 2 pigs died before 1 week due to pneumonitis. In the CYS group, 4 animals had motor impairment, and 3 of the 4 had paraplegia. The histological results were as follows: the control and MTX groups showed synovial metaplasia, inflammatory reaction, crystal deposits, and giant cell reaction in the dura mater and muscle and all the animals in the CYS group had spinal cord and muscular necrosis.
Conclusions:
Massive cement leak after vertebroplasty with PMMA loaded with cisplatin is extremely toxic to the spinal cord and muscles around the spine. Therefore, its use cannot be recommended for the treatment of vertebral metastases. Using PMMA loaded with methotrexate seems to be a safe procedure, but further research is needed.
Insights
Cement leaks containing cisplatin during vertebroplasty are toxic to the spine. Methotrexate-loaded cement appears safe, but further research is needed for vertebral metastases treatment.
Area of Science:
- Orthopedics
- Oncology
- Toxicology
Background:
- Vertebroplasty is a common procedure for vertebral fractures.
- Polymethylmethacrylate (PMMA) cement is used to stabilize vertebrae.
- Antiblastic drugs are sometimes loaded into PMMA for targeted cancer treatment.
Purpose of the Study:
- To evaluate the safety and toxicity of PMMA cement loaded with antiblastic drugs (methotrexate and cisplatin) when leaked during vertebroplasty.
- To assess the clinical and histological effects on spinal cord, nerve roots, and surrounding muscles in a porcine model.
Main Methods:
- Twenty-five pigs underwent vertebroplasty with either PMMA alone (control), PMMA with methotrexate (MTX), or PMMA with cisplatin (CYS).
- Massive epidural and prevertebral cement leaks were induced at two vertebral levels.
- Animals were monitored clinically, and tissues were analyzed histologically two weeks post-procedure.
Main Results:
- The control group showed no adverse effects.
- The MTX group experienced two deaths due to pneumonitis.
- The CYS group exhibited significant motor impairment, including paraplegia, and extensive spinal cord and muscular necrosis.
Conclusions:
- Massive leaks of cisplatin-loaded PMMA during vertebroplasty are highly toxic to the spinal cord and paraspinal muscles, precluding its use for vertebral metastases.
- PMMA loaded with methotrexate appears to be a safer alternative, warranting further investigation.
