Clinical Outcome and Histological Findings After Induced Leakage of PMMA Loaded With Methotrexate and Cisplatin During Vertebroplasty: Experimental Model in Pigs

Overview

Journal Global Spine J

Publisher Sage Publications

Date 2021 Feb 19

PMID 33601909

Authors

Alvaro Silva Gonzalez

Rafael Llombart-Blanco

Marcela Gallegos Angulo

Carlos Villas Tome

Matias Alfonso Olmos-Garcia

Affiliations

Soon will be listed here.

Abstract

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.

References

Urrutia J, Bono C, Mery P, Rojas C . Early histologic changes following polymethylmethacrylate injection (vertebroplasty) in rabbit lumbar vertebrae. Spine (Phila Pa 1976). 2008; 33(8):877-82. DOI: 10.1097/BRS.0b013e31816b46a5. View

Fisher C, DiPaola C, Ryken T, Bilsky M, Shaffrey C, Berven S . A novel classification system for spinal instability in neoplastic disease: an evidence-based approach and expert consensus from the Spine Oncology Study Group. Spine (Phila Pa 1976). 2010; 35(22):E1221-9. DOI: 10.1097/BRS.0b013e3181e16ae2. View

Togawa D, Bauer T, Lieberman I, Takikawa S . Histologic evaluation of human vertebral bodies after vertebral augmentation with polymethyl methacrylate. Spine (Phila Pa 1976). 2003; 28(14):1521-7. View

Bartels R, Feuth T, van der Maazen R, Verbeek A, Kappelle A, Grotenhuis J . Development of a model with which to predict the life expectancy of patients with spinal epidural metastasis. Cancer. 2007; 110(9):2042-9. DOI: 10.1002/cncr.23002. View

Ziu M, Traylor J, Paxman J, Goodgame B . Stereotactic Vertebroplasty for Spinal Metastases with Multilevel Bilateral Pedicle Fractures: A Technical Note. Cureus. 2019; 11(2):e4123. PMC: 6478491. DOI: 10.7759/cureus.4123. View

Choi D, Fox Z, Albert T, Arts M, Balabaud L, Bunger C . Rapid improvements in pain and quality of life are sustained after surgery for spinal metastases in a large prospective cohort. Br J Neurosurg. 2016; 30(3):337-44. DOI: 10.3109/02688697.2015.1133802. View

Wang F, Zhang H, Yang L, Yang X, Zhang H, Li J . Epidemiological Characteristics of 1196 Patients with Spinal Metastases: A Retrospective Study. Orthop Surg. 2019; 11(6):1048-1053. PMC: 6904662. DOI: 10.1111/os.12552. View

TARLOV I, Klinger H . Spinal cord compression studies. II. Time limits for recovery after acute compression in dogs. AMA Arch Neurol Psychiatry. 1954; 71(3):271-90. View

Rollins N, Winick N, Bash R, Booth T . Acute methotrexate neurotoxicity: findings on diffusion-weighted imaging and correlation with clinical outcome. AJNR Am J Neuroradiol. 2004; 25(10):1688-95. PMC: 8148738. View

10.

Flecknell P . Refinement of animal use--assessment and alleviation of pain and distress. Lab Anim. 1994; 28(3):222-31. DOI: 10.1258/002367794780681660. View

11.

GALIBERT P, Deramond H, Rosat P, Le Gars D . [Preliminary note on the treatment of vertebral angioma by percutaneous acrylic vertebroplasty]. Neurochirurgie. 1987; 33(2):166-8. View

12.

. Vertebral Augmentation Involving Vertebroplasty or Kyphoplasty for Cancer-Related Vertebral Compression Fractures: A Systematic Review. Ont Health Technol Assess Ser. 2016; 16(11):1-202. PMC: 4902848. View

13.

Bollen L, Dijkstra S, Bartels R, de Graeff A, Poelma D, Brouwer T . Clinical management of spinal metastases-The Dutch national guideline. Eur J Cancer. 2018; 104:81-90. DOI: 10.1016/j.ejca.2018.08.028. View

14.

Balestrino A, Boriani S, Cecchinato R, Parafioriti A, Gambarotti M, Gasbarrini A . Vertebroplasty shows no antitumoral effect on vertebral metastasis: a case-based study on anatomopathological examinations. Eur Spine J. 2020; 29(12):3157-3162. DOI: 10.1007/s00586-020-06555-9. View

15.

Yamashita S, Katsumi H, Sakane T, Yamamoto A . Bone-targeting dendrimer for the delivery of methotrexate and treatment of bone metastasis. J Drug Target. 2018; 26(9):818-828. DOI: 10.1080/1061186X.2018.1434659. View

16.

Jensen M, Kallmes D . Percutaneous vertebroplasty in the treatment of malignant spine disease. Cancer J. 2002; 8(2):194-206. DOI: 10.1097/00130404-200203000-00013. View

17.

Dunning E, Butler J, Morris S . Complications in the management of metastatic spinal disease. World J Orthop. 2012; 3(8):114-21. PMC: 3425630. DOI: 10.5312/wjo.v3.i8.114. View

18.

Nieuwenhuijse M, van Erkel A, Dijkstra P . Cement leakage in percutaneous vertebroplasty for osteoporotic vertebral compression fractures: identification of risk factors. Spine J. 2011; 11(9):839-48. DOI: 10.1016/j.spinee.2011.07.027. View

19.

Pellacani C, Eleftheriou G . Neurotoxicity of antineoplastic drugs: Mechanisms, susceptibility, and neuroprotective strategies. Adv Med Sci. 2020; 65(2):265-285. DOI: 10.1016/j.advms.2020.04.001. View

20.

Pountos I, Giannoudis P . Drug-eluting implants for the suppression of metastatic bone disease: current insights. Expert Rev Med Devices. 2018; 15(4):301-311. DOI: 10.1080/17434440.2018.1456336. View