SPINE Volume 33, Number 8, pp 877– 882 ©2008, Lippincott Williams & Wilkins Early Histologic Changes Following Polymethylmethacrylate Injection (Vertebroplasty) in Rabbit Lumbar Vertebrae Julio Urrutia, MD,* Christopher M. Bono, MD,† Pablo Mery, MD,* and Claudio Rojas, MD* Study Design. An ex vivo histologic study in rabbits. Objective. To evaluate the early histologic effects of polymethylmethacrylate (PMMA) injection on bone and intraosseous neural tissue following vertebroplasty in rabbit lumbar vertebrae. Summary of Background Data. Vertebroplasty with PMMA is performed to treat painful osteoporotic verte- bral fractures. Early pain relief has been consistently doc- umented, but its mechanism has not been elucidated. Among the mechanisms of pain relief may be the imme- diate stabilizing effects of the cement, and the exothermic reaction during curing, which may lead to intraosseous neural ablation. It has been well established that PMMA can induce thermal osteonecrosis after arthroplasty, but the potential for osteonecrosis after vertebroplasty has not been established. Previous studies have suggested that temperature elevations during cement curing may induce thermal bone necrosis. However, this cause-and- effect relationship has not yet been histologically studied in an animal model. Methods. Vertebroplasty with PMMA was performed at 2 levels in 12 New Zealand rabbits (24 levels); trochar insertion without PMMA injection was performed at 3 levels each of 2 control animals (6 levels). Sacrifice was performed 24 hours after the procedure. Histologic ex- amination was performed to evaluate the presence of bone or intraosseous neural tissue necrosis. Results. Half of the levels with PMMA showed evi- dence of necrosis at the bone-cement interface. Almost all (11 of 12) showed only focal necrosis, with only 1 speci- men showing necrosis along the entire periphery of the PMMA. The other 12 specimens and all control levels displayed no bone necrosis. There was no evidence of intraosseous neural tissue necrosis in control or PMMA- injected specimens. Conclusion. Injection of PMMA in rabbit lumbar ver- tebral bodies produces early, focal bone necrosis in only half of cases, suggesting that competency of the cement-bone interface is reasonable in most cases. No evidence of intraosseous neural tissue damage was found. Key words: polymethylmethacrylate, vertebroplasty, rabbit model, osteonecrosis, bone necrosis, neural abla- tion. Spine 2008;33:877– 882 Vertebroplasty is commonly performed to treat painful vertebral compression fractures from osteoporosis or metastatic tumors after nonoperative methods have failed. 1–11 By its design, it requires injection of bone ce- ment, most frequently polymethylmethacrylate (PMMA), which has been modified by the addition of barium sulfate to increase its radiopacity. Cement is in- jected into the vertebral body via a cannula that is in- serted under fluoroscopic guidance. First developed in France in the late 1980s 1 as a treatment for symptomatic vertebral body hemangiomas, initial use in the United States was in 1997 for osteoporotic compression frac- tures. 9 A multitude of studies have shown major im- provements in pain, mobility, and function after the ver- tebroplasty with a low risk of complications. 2–13 A consistently reported finding is that pain relief is observed almost immediately after the procedure, appre- ciable by postoperative day 1 or 2. 3,6,7 Nonetheless, it is still unclear why pain relief is achieved so quickly. Among the theories proposed to explain the pain relief are thermal necrosis of surrounding tissues and nerve ends, chemical toxicity, or mechanical stabilization of the fracture. 8 Some have suggested that thermal necrosis produced by the exothermic reaction generated during polymerization of PMMA can lead to ablation of the intraosseous (presumably nociceptive) neural tis- sue. 14 –21 The concern regarding thermal bone necrosis is still controversial, as to date, there has been no obvious evidence of early bone necrosis to support it. Others have speculated that nerve endings within the vertebral body can be ablated by the cytotoxicity of the PMMA mono- mer. 14,22,23 Perhaps most popular is the belief that the stiffness of the cured PMMA provides mechanical stabi- lization of the fractured vertebra, a mechanism that is independent of the cement’s exothermal reaction. 24 –29 Importantly, these theories are based primarily on ex- trapolation of data from studies of PMMA for total joint surgery. Thus, there is limited histologic data specific to PMMA use in the spine. While a plethora of biomechanical investigations have been performed, to the authors’ knowledge no previous study has evaluated the early (i.e., within 24 hours) tissue changes after PMMA injection into vertebral bodies. Two examinable tissue changes are bone necrosis and From the *Department of Orthopedic Surgery, Pontificia Universidad Catolica de Chile, Santiago, Chile; and †Harvard Medical School, De- partment of Orthopedic Surgery, Brigham and Women’s Hospital, Boston, Massachusetts. Acknowledgment date: August 17, 2007. First revision date: October 25, 2007. Second revision date: November 13, 2007. Acceptance date: November 13, 2007. The legal regulatory status of the device(s)/drug(s) that is/are the sub- ject of this manuscript is not applicable in my country. Institutional funds were received in support of this work. No benefits in any form have been or will be received from a commercial party related directly or indirectly to the subject of this manuscript. Address correspondence and reprint requests to Dr. Julio Urrutia, De- partment of Orthopedic Surgery, Pontificia Universidad Catolica de Chile, Marcoleta 352 Santiago, Chile; E-mail: jurrutia@med.puc.cl 877