Minimally Invasive Procedures for Vertebral Compression Fractures

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Minimally Invasive Procedures for Vertebral Compression Fractures Ronil V. Chandra | Thabele M. Leslie-Mazwi | James D. Rabinov | Albert J. Yoo | Joshua A. Hirsch

One in two women and one in five men older than 50 years will experience an osteoporotic fracture, which can result in substantial pain, morbidity, and health care utilization. A new osteoporotic vertebral fracture occurs every 22 seconds; 1.4 million occur worldwide every year.1 The majority are asymptomatic or result in tolerable symptoms, with only a third of patients with a new fracture seeking medical attention.2 In the vast majority, the acute back pain symptoms subside over a period of 6 to 8 weeks as the fracture heals.3 Vertebroplasty and kyphoplasty are minimally invasive, image-guided procedures that involve the injection of cement into a fractured vertebral body (Figs. 67.1 and 67.2). The majority of these vertebral augmentation procedures are performed in a small subset of patients with symptomatic osteoporotic compression fractures that fail conservative medical therapy. Failure of medical therapy is variably defined but can be considered if the pain persists at a level that severely compromises mobility or activities of daily living despite analgesic therapy or if unacceptable side effects such as confusion, sedation, or constipation occur as a result of the doses of medication required to reduce the pain to tolerable levels. Notably, the first report of augmentation (published in 1987) was for neoplastic disease.4 As survival rates in cancer patients continue to improve, symptomatic neoplastic vertebral fractures and neoplastic vertebral tumors have increased in prevalence. A selected subgroup of these patients, in particular, those with symptomatic fractures from multiple myeloma and metastasis that fail to respond to conservative therapy, also benefit from vertebral augmentation.5 The primary goal of augmentation is pain relief and enhanced functional status with the secondary goal of vertebral body stabilization in cases of fracture. Key points, indications for, and contraindications to vertebral augmentation are summarized at the end of the chapter.

CONSERVATIVE MEDICAL THERAPY FOR VERTEBRAL COMPRESSION FRACTURES The goals of conservative therapy are pain reduction (with analgesics, bed rest, or both), improvement in functional status (with orthotic devices and physical therapy), and prevention of future fractures (with vitamin D and calcium supplementation and bisphosphonate therapy). Although conservative management of those with mild pain and no limitation of function is appropriate, conservative

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treatment of those with more severe pain or limitation of function is not benign. In this cohort, conservative therapy often involves a period of bed rest, which may lead to undesirable side effects such as loss of bone mass and muscle strength, decubitus ulceration, and venous thromboembolic disease, all of which can prolong the recovery period and result in loss of independence. Bone loss occurs at a rate of approximately 2% per week,6 muscle strength is reduced by 10% to 15%,7 and infectious complications can lead to septicemia and osteomyelitis. Moreover, the presence of fracture or malignancy combined with bed rest elevates the risk for venous thromboembolic disease in this cohort. Overall, the complications of prolonged bed rest, combined with opioid analgesic use and its associated side effects, can result in a vicious cycle of physical deconditioning, poor nutrition, and subsequent increased risk for vertebral insufficiency.

TECHNICAL ASPECTS OF VERTEBRAL AUGMENTATION Evaluation of patients for vertebral augmentation should identify those likely to benefit from vertebral augmentation, as well as screen for contraindications. The decision to proceed with treatment must be based on a good history, physical examination, appropriate laboratory evaluation, and imaging, as summarized in Boxes 67.1 and 67.2.

SEDATION Analgesia is typically necessary for vertebroplasty and kyphoplasty. In the majority of cases, it is achieved with a combination of local analgesics (e.g., lidocaine with bicarbonate or bupivacaine) and moderate sedation (intravenous midazolam and fentanyl). In some cases, general anesthesia is needed to provide adequate comfort and safety, particularly in patients at high risk for airway or respiratory complications with prone positioning or those with significant preprocedure narcotic analgesic requirements. However, having the patient awake is desirable because it allows feedback (e.g., increasing pain, neurologic dysfunction) that can alert the operator to potential complications. In all cases, continuous monitoring is performed with a minimum of electrocardiography, blood pressure measurements, and pulse oximetry. Sedation and monitoring are performed by anesthesiologists, nurse anesthetists, or certified nursing

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Figure 67.1  Vertebroplasty involves insertion of a needle into the vertebral body (A) with subsequent delivery of cement (B) into the vertebral body.

Figure 67.2  Kyphoplasty. Once access to the vertebral body is achieved (A), the inner stylet is removed and a balloon tamp is inflated within the vertebral body (B) to create a cavity within the bone (C) into which cement is delivered (D).

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Box 67.1 Indications for and

Contraindications to Vertebral Augmentation

Indications 1.  Treatment of symptomatic osteoporotic vertebral body fractures that are refractory to conservative medical therapy 2. Treatment of symptomatic vertebral bodies weakened or fractured because of neoplasia that are refractory to medical therapy Absolute Contraindications . Active systemic infection, in particular, spinal infection 1 2. Uncorrectable bleeding diathesis 3. Insufficient cardiopulmonary health to safely tolerate sedation or general anesthesia 4. Myelopathy resulting from fracture retropulsion or epidural tumoral extension 5. Known allergy to bone cement Relative Contraindications (Should Be Treated Only by Experienced Practitioners) 1. Marked loss of vertebral body height (greater than 75% loss of height), which makes the procedure more difficult since there may be little space for placement of a cannula. 2. Vertebroplasty above T5, which is challenging because of the small size of the vertebral bodies and pedicles. The shoulders often limit fluoroscopic imaging at these levels. 3. Severe osteopenia resulting in poor visualization of osseous structures on fluoroscopy, which increases the risk for improper needle placement and cement leakage. This can be overcome with guidance by computed tomography. 4. Disruption of the posterior cortex, which increases the risk for posterior cement leakage and therefore the risk for spinal cord or nerve root compression. This is frequently seen with burst fractures and neoplasm. The integrity of the posterior cortex is best evaluated with computed tomography. 5. Substantial canal narrowing (without neurologic dysfunction), which increases the risk that even a small amount of cement leakage will produce neurologic compromise. 6. Retropulsion of fracture fragments, which increases the risk for further canal compromise with vertebral augmentation, particularly if the posterior vertebral body wall is unstable. 7. Epidural extension of tumor, which in the setting of pathologic fractures results in significantly higher rates of spinal canal leakage than osteoporotic fractures do.

personnel. In patients with substantial preexisting respiratory or cardiac disease, an anesthesiologist can be asked to evaluate the patient and determine whether monitored anesthesia care is warranted. The patient should not eat or drink for at least 4 to 6 hours before the procedure.

PATIENT POSITIONING Prone or oblique prone is the ideal patient position for thoracic and lumbar procedures. In practical terms, we allow patients an amount of freedom to place themselves in the prone oblique position should it promote greater comfort throughout the procedure. This can introduce 10 to 15 degrees of obliquity, depending on the patient’s position. In addition to the clear advantage of easy access, this position with proper cushion support under the upper part of the chest and lower

part of the abdomen maximizes extension of the fractured segments, thereby promoting reduction of kyphosis.9 The patient's arms should be placed sufficiently toward the head to keep them out of the path of the fluoroscope. Analgesia should be considered before placement on the table because this part of the procedure may be quite painful. Particular care must be taken when transferring patients who are aged or have osteoporosis or myelomatous infiltration since this may result in new rib or vertebral fractures.

ANTIBIOTIC PROPHYLAXIS AND SKIN PREPARATION The risk for infection is minimized by following standard operating room guidelines for sterile preparation of the skin, draping, operator scrubbing, and use of sterile gowns, masks, and gloves. Few data support or oppose antibiotic administration, but there are reports of spine infections after these procedures,10,11 and the presence of polymethyl methacrylate (PMMA) makes these infections difficult to treat successfully. We routinely use antibiotic prophylaxis. Prophylaxis for these procedures comes in one of two forms. An intravenous antibiotic such as cefazolin (1 g) or clindamycin (600 mg with penicillin allergy) may be administered before skin incision. Alternatively, the PMMA may be mixed with an antibiotic, such as tobramycin (1.2 g), as the cement is being prepared; this practice has diminished in favor of intravenous antibiotics.

NEEDLE PLACEMENT The most important aspect of needle placement is to keep the needle trajectory lateral to the medial cortex and superior to the inferior cortex of the pedicle. This prevents entry of the needle into the spinal canal or neural foramen. The needle may be placed via a transpedicular or parapedicular approach. In the transpedicular approach, the needle is directed from the posterior surface of the pedicle, through the length of the pedicle, and into the vertebral body. The long intraosseous path protects the postganglionic nerve roots and other soft tissues. However, the pedicle configuration can limit one's ability to achieve a final needle tip position near the midline. In the parapedicular approach, the needle is directed along the lateral surface of the pedicle, with the pedicle being penetrated along its path or the vertebral body at its junction with the pedicle. This approach may permit more medial tip placement, which can be useful during treatment of levels with anatomically small pedicles, in particular, in the thoracic spine. For either of these approaches there are multiple potential image guidance strategies, including anteroposterior (AP) and end-on (“down the barrel”) views, with the latter technique involving ipsilateral oblique rotation of the image intensifier to place the fluoroscopy beam and needle track parallel to each other. The following description assumes the use of two perpendicular image intensifiers simultaneously (biplanar fluoroscopy): 1. Rotate the image intensifier to a true AP position by aligning the spinous process midway between the pedicles (Fig. 67.3). 2.  Change the craniocaudad angulation by bringing the pedicles to the midportion of the vertebral body. Use

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Box 67.2 Preprocedure Workup Identify patients who will probably benefit from vertebral augmentation. Screen for absolute contraindications. Document failure of conventional medical therapy. Symptoms: • Fractures possibly occurring with little or no trauma • Deep pain with a sudden onset • Midline location • Exacerbation by axial mechanical loading (worsened with standing or weight bearing and often at least partially relieved by recumbency) • Exacerbation with motion (especially flexion) • Referred lateral radiation in a dermatomal pattern possibly present Signs: • Point tenderness at the spinous process of the fractured vertebra. Local signs may be surprisingly absent. However, up to 30% of patients may have subjective off-midline pain or tenderness over nontarget vertebrae and still gain significant benefit.8 • Localization to a specific level if possible is important in targeting treatment in patients who have multiple compression fractures, some of which may be healed and do not require treatment. In difficult cases, examination can be performed with fluoroscopic assistance to localize the pain to a specific anatomic level. Assess lower extremity neurologic function.

Laboratory evaluation: • Screen for infection, coagulopathy, and metabolic abnormality. • Additional tests such as urinalysis, electrocardiography, and/or chest radiography are left to the discretion of the practitioner. Imaging: • Its role is to confirm the clinical diagnosis, identify and assess the acuity of the acute painful fracture, identify potential difficulties, and plan the procedure. • MRI with STIR or T2-weighted sequences with fat saturation should be obtained in all patients if not contraindicated. These sequences identify marrow edema, which distinguishes acute from chronic fractures. MRI also distinguishes between benign osteoporotic and pathologic fractures and assesses the degree of fracture retropulsion, epidural tumor extension, spinal canal compromise, and compression of the spinal cord or nerve roots. Fracture clefts appear as a linear band of T1 hypointensity and T2 hypointensity or hyperintensity within the vertebral body. • In patients who cannot undergo MRI, nuclear scintigraphic bone scanning or single-photon emission computed tomography in combination with CT are the tests of choice. Acute fractures will take up the injected 99mTc-MDP tracer in much higher concentrations; CT evaluates bone integrity and the spinal contents. In patients with pathologic fractures, CT also helps define the extent of sclerosis and posterior wall osteolysis, which in turn predict increased technical challenges associated with the procedure.

CT, computed tomography; MDP, methylene diphosphate (medronate); MRI, magnetic resonance imaging; STIR, short tau inversion recovery.

the lateral fluoroscopic view to aid in determination of the correct craniocaudad adjustment required. a. For the end-on view, rotate image intensifier approximately 20 degrees ipsilateral to the target pedicle so that the medial cortex of the pedicle is at the middle third of the vertebral body. The vertebra adopts the “Scotty dog” configuration. Place the needle so that it is "end on" to the image intensifier and appears as a dot. 3. Plan the trocar trajectory. For the AP and partial ipsilateral oblique views, the trocar entry site should be at the 3-o’clock position of the right pedicle or the 9-o’clock position of the left pedicle for the transpedicular approach. In the end-on view, it is centered within the circle formed by the cortex of the pedicle. For parapedicular approaches an entry site just lateral to the 3- or 9-o’clock position of the pedicular cortex is best. 4. Anesthetize the skin and periosteum by subcutaneous injection of lidocaine or bupivacaine via a 22-gauge needle along the planned trajectory. Use this smaller-gauge needle to assess and adjust the planned trajectory. 5. Make a small vertical skin incision (allows easier craniocaudal needle angulation), and insert the 11- or 13-gauge diamond-tipped needle stylet (sheathed in a cannula). 6. Advance the needle to the bone surface while making small corrections in craniocaudad angulation on the true lateral view (care is needed to angle the image intensifier so that a true lateral view is obtained). For the parapedicular approach, the position at which bone is encountered

(i.e., at the junction of the pedicle and vertebral body) is more anterior on the lateral view. 7.  Once in the bone, advance the needle either with a drilling motion and controlled forward pressure or by carefully tapping the needle handle with an orthopedic mallet. 8.  Maintain a true AP view of the image intensifier for advancement of the needle unless using the end-on view, in which case the needle is kept as a dot during initial placement through the pedicle. The needle must remain lateral to the medial cortex of the pedicle until it has traversed the entire pedicle on the lateral view. 9.  Once the needle has traversed the pedicle, one can replace the diamond-tipped needle with a straight beveltipped needle or curved needle for better maneuverability (Fig. 67.4). Advance the needle further via the lateral view to the anterior third to quarter of the vertebral body. ADDITIONAL STEPS FOR KYPHOPLASTY For vertebroplasty, the PMMA is delivered through the cannula after placement of the needle as just described. Kyphoplasty involves the additional steps of balloon tamp insertion and inflation to create a cavity within the bone (Fig. 67.5). For kyphoplasty, pull the cannula back to the posterior aspect of the vertebral body to allow the insertion of the balloon tamp. After the needle stylet is removed, insert the balloon tamp through the cannula and slowly inflate with iodi­ nated contrast medium. The balloon is attached to a locking syringe with a digital manometer

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Figure 67.3  Initial positioning of the needle for a transpedicular approach. A, Anteroposterior (AP) fluoroscopic image. The image intensifier is first rotated to a true AP position to align the spinous process midway between the pedicles (vertical dotted line). The craniocaudad angulation is changed to bring the pedicles to the midportion of the vertebral body (horizontal dotted lines). B, Lateral fluoroscopic image. The image intensifier is rotated to a true lateral position by overlapping the cortices of both pedicles and ensuring that the posterior margin of the vertebral body is aligned (dotted lines). Note that the entire needle trajectory within the vertebral body should be considered during initial transpedicular access for optimal final needle position (solid line). C, Near “end-on” projection during needle placement with preservation of the medial and inferior cortices of the pedicle. Note that a “T-grip” needle handle can obscure bony landmarks and slight rotation of the image intensifier may be required. D, Midline needle position obtained via a unilateral transpedicular approach, which can be achieved with larger target pedicles, typically in the lumbar vertebrae.

(Fig. 67.6). Monitor the inflation with both the pressure transducer and intermittent fluoroscopy. Continue inflation until one of two conditions is met: the system reaches significant pressure or maximum balloon volume or further inflation results in patient discomfort. Balloon placement can be either unipedicular or bipedicular. Deflate and then remove the balloon.

CEMENT PLACEMENT The consistency of the cement, when ready for injection, is similar to that of toothpaste. Wong and Mathis recommend a drip test, in which the cement should ball up at the end of the needle and not drip downward, which will result in a cement consistency that is slightly more viscous than

toothpaste.12 Working time varies from 10 to 20 minutes, depending on temperature and the specific PMMA formulation being used. A variety of delivery systems are available for the cement. These systems vary from a few 1-mL syringes with a spatula and a mixing bowl to self-contained delivery devices. A screw-syringe injector with long, flexible delivery tubing has the advantage of minimizing exposure of the operator to radiation.13

VERTEBROPLASTY • After removing the needle stylet, fill the cannula with saline to prevent pressurized injection of air and air embolism. Connect the delivery system to the cannula and inject the cement slowly.

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Figure 67.4  Photographs of typical vertebroplasty needles. A, Typical coaxial vertebroplasty needle—the inner stylet locks into the outer cannula. Note the large handles to facilitate insertion and removal from the bone. Manufacturers may use different colored or marked handles to indicate the type of needle tip (magnified in B). A needle with a beveled tip can be used to facilitate directing the needle along the desired trajectory.

Figure 67.6  Balloon kyphoplasty. The balloon is attached to a digital manometer, which allows assessment of balloon pressure. Note the long flexible tubing, which permits the operator’s hands to remain out of the primary radiation beam during fluoroscopic assessment of balloon inflation.

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Figure 67.5  Additional steps for kyphoplasty. A, Lateral fluoroscopic image. The unipedicular needle has been placed into the anterior third of the T10 vertebral body. B, The needle is withdrawn to the posterior third of the vertebral body and the inner stylet removed. C, The balloon tamp is introduced into the needle track and inflated to create a cavity within the bone. D, Cement opacifies both the cavity and extends into adjacent trabecular bone.

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• Monitor carefully with fluoroscopic imaging to ensure that the cement remains within the vertebra. Posterior or posterolateral leakage could result in irritation of or damage to the spinal cord or nerve roots and should be avoided. New pain with a different character should prompt an immediate pause in the procedure and additional views. • End points for cement injection include passage of cement beyond the marrow space or cement reaching the posterior quarter of the vertebral body on the lateral projection. In the case of cement leakage, one may wait 1 to 2 minutes to allow the cement to harden and then reinject to see whether the cement is redirected within the vertebral body.14 Ideally, the cement will extend across the midline to the opposite pedicle by the end of the injection. The optimal volume of cement remains a matter of controversy. • The final portion of cement may be delivered by inserting the needle stylet. Alternatively, the cement may be allowed to harden and the needle removed with a gentle rocking motion to ensure that the cement within the cannula separates at the tip of the cannula.

KYPHOPLASTY • The cavity created by the balloon tamp allows injection of cement that is more viscous than that typically used for vertebroplasty. The cavity and more viscous cement theoretically minimize the risk for extravasation of cement. Sufficient time is allowed for the cement to reach a doughy consistency, with loss of the "sheen" of the initially mixed cement. • Many practitioners use manual bone filler devices to inject cement, although one can use injector systems. The delivery system is connected to the cannula and the cement is injected slowly under fluoroscopic guidance. The cavity is filled with cement from anterior to posterior until it matches or slightly exceeds the volume of the inflated balloon tamp.

CONTROVERSIES AND SPECIAL TOPICS BIPEDICULAR VERSUS UNIPEDICULAR APPROACH Vertebroplasty and kyphoplasty can be performed with placement of bilateral needles or a single needle.15 In either case the goal is to place cement across the midline within the vertebral body—we use placement of PMMA to the opposite pedicle as our general landmark. Therefore, use of a single needle with a relatively medial position of the needle tip is sufficient in many cases. If a unilateral approach is attempted during kyphoplasty and balloon expansion does not cross midline, a second system may then be placed on the other side, depending on the distribution of cement fill. In many cases, cement fill will continue across the midline, thereby obviating the need for a second needle. Moreover, hemivertebral fill (cement traverses <10% of the contralateral unfilled vertebra) has been shown to be as efficacious in reducing pain and improving function without an increased risk for fracture.16 Importantly, there is no statistically significant difference in the pain relief achieved with unipedicular and

bipedicular vertebroplasty17 or kyphoplasty.18 There are advantages to each approach. Advantages of a unipedicular approach include a decrease in procedure time and elimination of the risk associated with placement of a second needle. A unipedicular approach is also associated with lower rates of cement leakage.19 The major advantage of a bipedicular approach is that access is typically transpedicular with a less aggressive lateral to medial approach that may result in less paravertebral vessel and nerve injury and a potential biomechanical advantage for bilateral delivery of cement.

VOLUME OF CEMENT INJECTED The optimal volume of cement is a matter of controversy, with some practitioners advocating injection of maximal amounts of cement to completely fill the vertebral body and others advocating lower cement volumes with an emphasis on safety. The theoretical goal of more complete filling is to achieve restoration of biomechanical strength within the vertebral body to prevent refracture without creating excessive stiffness that may be transmitted to the adjacent levels. Based on an in vitro biomechanical study, Mathis and Wong recommended filling 50% to 70% of the residual volume of the vertebral body with cement.20 However, much smaller amounts of cement (as little as 0.5 mL) appear to result in similar clinical outcomes as do larger-volume injections in terms of the primary goal of pain relief, with no association between the volume of cement injected and the clinical outcomes of pain and medication use.20 The decreased risk for extravasation of cement with smaller-volume injections and meticulous attention to the end-of-injection criteria outlined earlier favor an approach using a smaller volume of cement.

VERTEBRA PLANA When the vertebral body loses 70% of its original height, safe needle placement becomes a challenge. According to Stallmeyer and associates, at least 8 mm of residual height is required for cannula placement.21 Vertebra plana often adopts a bow-tie configuration in which the center is compressed the most. This usually requires a lateral needle position with placement of bilateral needles.22 Only a small amount of cement is needed to achieve pain relief.23 If there is a cystic cleft within the fracture (Kummel’s disease), the needle may be placed near the midline within the cleft in the hope of expanding the height of the vertebra during needle placement and cement injection.

FRACTURES WITH AN INTRAOSSEOUS VACUUM PHENOMENON (KUMMEL’S DISEASE) The intraosseous vacuum phenomenon is thought to be related to osteonecrosis. A fluid-filled cleft seen on magnetic resonance imaging (MRI) is an equivalent finding. Pain in this setting is believed to arise from motion between the unhealed fracture fragments. In some cases this motion can even be seen under fluoroscopy as the height of the vertebral body changes with respiration. Prone positioning during the procedure promotes restoration of height because of the traction placed across the vertebral body. The needle

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should be placed into or as close to the cleft as possible so that cement will fill the cleft. Vertebral augmentation yields significant rates of pain relief in the setting of an intraosseous vacuum phenomenon,24,25 and in our experience it can provide considerable restoration of height. It is important to keep the patient prone for 15 to 20 minutes after injection of the cement to allow the cement to harden within the cleft before moving the patient off the fluoroscopy table.

MALIGNANT FRACTURES WITH POSTERIOR WALL OSTEOLYSIS OR EPIDURAL TUMOR EXTENSION Although vertebral augmentation may be performed in the setting of posterior wall osteolysis or epidural tumor extension, there should be heightened awareness of the potential neurologic complications related to epidural extension of cement or posterior displacement of tumor. In a study of 51 patients with a vertebral lesion and epidural extension treated by vertebroplasty, 30% had preprocedure symptoms of partial or complete cord compression/cauda equina syndrome.26 These patients were terminally ill and did not undergo surgical decompression because their paraplegia was deemed irreversible (present for more than 1 month or associated with spinal cord atrophy) or their general condition was a contraindication to surgery. Although no further clinical deterioration was observed in this subgroup after vertebroplasty, in 1 of the 36 patients without neurologic symptoms, cauda equina syndrome developed 2 days after vertebroplasty and required surgical decompression.26 Cement leakage (as detected on postprocedure computed tomography [CT]) occurred in 62%, with half of these leaks extending into the epidural space. Importantly, extension of cement beyond the confines of the vertebral body but within the epidural tumor was still classified as a leak.27 Nonetheless, the aforementioned was the only symptomatic cement leak. No systemic complications occurred. Analgesic efficacy, based on 50% or greater improvement in pain as compared with baseline, was impressive—94% (48 of 51 patients) at day 1, 86% (31 patients) at 1 month, 83% (19 patients) at 6 months, and 92% (11 patients) after 1 year (data are from surviving patients).26 Safeguards to prevent complications in this cohort include performing the procedure with the patient awake (new pain may be the first sign of dangerous cement leakage) and more modest cement injection than used for routine cases. Limiting the cement to the anterior two thirds of the vertebral body may be a good rule of thumb, as well as injection of thicker cement, which may in turn reduce the risk for epidural cement leakage.28

SAFETY OF MULTILEVEL TREATMENT A patient scheduled for vertebral augmentation may have multiple fractures that require treatment. Ideally, all the levels would be treated at one time. However, treating an excessive number of levels in a single session raises many concerns, including PMMA toxicity, difficulty for the elderly to lie prone and cooperate for the extended amount of time that this would require, discomfort after the procedure related to placement of multiple needles, and fat emboli being extruded from marrow during the cement injection. There have been two reported deaths in patients who underwent vertebral augmentation at eight or more levels.29 Even

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though there is no established guideline, a good rule of thumb is to treat a maximum of three levels per session.30,31

OUTCOMES ASSOCIATED WITH VERTEBRAL AUGMENTATION The mechanism by which vertebroplasty and kyphoplasty relieve pain is uncertain.32 Hypotheses include mechanical stabilization of mobile fracture fragments, thermal or chemical neurolysis, or inherent tumoricidal or cytotoxic effects on malignant fractures. A cadaveric study has also demonstrated new bone formation after PMMA injection.33 Two highly publicized placebo-controlled randomized clinical trials on vertebroplasty have been published in the New England Journal of Medicine. Both trials used a sham procedure in the placebo arm that involved injection of local anesthetic down to the periosteum of the pedicle34 or injection of local anesthetic combined with passage of a 13-gauge needle to rest on the lamina.35 Both studies found that there was no significant reduction in pain or pain-related disability in patients undergoing vertebroplasty versus the sham procedure. The INvestigational Vertebroplasty Efficacy and Safety Trial (INVEST) included 131 patients, with 68 randomized to vertebroplasty and 63 to the sham procedure.34 Even though at 1 month there was a trend toward a higher rate of clinically meaningful improvement in pain (30% decrease from baseline), no statistical difference in regard to pain scores, back pain–related disability, or quality of life was noted.34 Buchbinder and colleagues studied 78 patients, with 38 randomized to vertebroplasty and 40 to the sham procedure.35 After the procedure, both groups had similar improvements in pain, physical functioning, and quality of life. There were no significant differences between the groups at 1 week, 1 month, 3 months, and 6 months of follow-up.35 These reports are in contrast to previous retrospective case series that had documented impressive rates of pain relief with these procedures.36 The New England Journal of Medicine trials were criticized for potential inclusion of patients with chronic fractures of up to 12 months in duration. The average duration of back pain was 18 weeks in INVEST, with a third of all randomized patients having pain for longer than 6 months. The trial of Buchbinder and coworkers had four patients randomized after 6 months. In the INVEST trial, marrow edema seen on MRI or increased uptake on bone scanning was required only for fractures of an uncertain age (rate of use was not reported). In the trial of Buchbinder and colleagues, MRI demonstrating marrow edema or a fracture line (or both) was required; however, determination of bone marrow edema was not described. Further criticisms include inconsistent use of physical examination, difficulties in recruitment, and absence of a control group without intervention. Since then, the vertebroplasty versus conservative treatment in acute osteoporotic vertebral compression fractures (VERTOS II) investigators37 performed a nonblinded trial in which 202 patients with severe back pain for 6 weeks or less, focal tenderness at the fracture level, and MRI demonstration of bone edema were randomized equally into the vertebroplasty or conservative arms. All patients were prescribed analgesics that were individually titrated, bisphosphonates, and calcium and vitamin D

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supplements. Vertebroplasty was performed at a mean of 5.6 weeks after the onset of symptoms. There were statistically significant reductions in mean visual analog scale (VAS) scores in favor of vertebroplasty at 1 month (P < 0.0001), with the benefit persisting at 1 year (P < 0.0001).37 There were significant reductions in the use of drugs in the vertebroplasty group at 1 day (P < 0.0001), 1 week (P = 0.001), and 1 month (P = 0.033).37 Moreover, significant pain relief (reduction in VAS score of 3 or more points) was achieved earlier and in more patients after vertebroplasty (29.7 days; 95% confidence interval [CI], 11.45 to 47.97) than after conservative treatment (115.6 days; 95% CI, 85.87 to 145.40).37 Notably, the same investigators have already planned VERTOS IV—a prospective, multicenter, randomized controlled trial using the same strict inclusion criteria as in VERTOS II that is designed to compare pain relief after vertebroplasty and a sham intervention in patients with acute osteoporotic vertebral compression fractures.38 The FREE trial was another large trial supporting the efficacy of vertebral augmentation. A total of 300 patients were randomized to undergo kyphoplasty (n = 149) or conservative therapy (n = 151).39 Fractures were to have a minimum of 15% loss of height and MRI evidence of edema. Although both osteoporotic and malignant fractures were included, 96% of the fractures were related to primary osteoporosis. At randomization, fractures were a mean of 6 weeks old, kyphoplasty was performed at a mean of 7 days after randomization, and patients with fractures older than 3 months were excluded. The primary outcome measure was the mean 36-Item ShortForm Health Survey (SF-36) physical component summary (PCS) scale, a validated global quality-of-life measure weighted on physical ability.39 Statistically significant improvements in SF-36 PCS scores in favor of kyphoplasty were noted at 1 month (P < 0.0001) and 12 months (P = 0.0004). There were greater reductions in Roland-Morris Disability Questionnaire (RDQ) scores in favor of kyphoplasty at 1 month (P < 0.0001) and 12 months (P = 0.0012).39 Patients in the kyphoplasty group also had greater reductions in back pain scores, lower rates of narcotic analgesic use, and fewer days of restricted activity than did those managed with conservative therapy.39 By 12 months, the differences between the conservative therapy arm and kyphoplasty group were diminished, most likely because of fracture healing.39 Further randomized controlled trial evidence comes from the Cancer Patient Fracture Evaluation (CAFE) study, which reported a benefit of kyphoplasty over conservative therapy for malignant painful vertebral compression fractures.5 The CAFE study investigators recruited 134 patients with malignant fractures at 22 sites in Europe, the United States, Canada, and Australia. Approximately 50% of the patients had breast, lung, or prostate cancer metastasis, and 40% had multiple myeloma–related fractures. Patients with osteoblastic tumors, primary bone tumors such as osteosarcoma, or plasmacytoma at the index compression fracture were excluded. Patients were randomly assigned to kyphoplasty (n = 70) or conservative therapy (n = 64). The median estimated symptomatic fracture age was 3.5 months (interquartile range, 1.2 to 6.8); 87 of 129 patients had edema on MRI. The primary end point was back-specific functional status as measured by the RDQ at 1 month. There was a statistically significant reduction in RDQ scores in favor of kyphoplasty at 1 month (P < 0.0001).5 The mean RDQ score in the kyphoplasty

group was reduced from 17.6 at baseline to 9.1 at 1 month, as opposed to a mean change in score from 18.2 to 18.0 in the control group, and the kyphoplasty treatment effect on the RDQ score was −8.4 points at 1 month (95% CI, −7.6 to −9.2; P < 0.0001). Patients in the kyphoplasty group also had greater reductions in back pain—both groups had baseline mean back pain score of 7.3; the mean score at 7 days was 3.5 versus 7.0 in the conservative arm (P < 0.0001), which remained significant at 1 month (P < 0.0001). In addition, there were significant reductions in analgesic use and days of bed rest and improvement in quality of life (as measured by the SF-36 PCS) and Karnofsky performance status in the kyphoplasty group versus the conservative arm. These improvements in pain, overall functional status, and quality of life continued for the 12 months of the study period.5 With regard to longer-term outcomes, there are few data. Two-year outcome data from the FREE trial revealed that although there were no longer statistically significant differences in SF-36 PCS or RDQ scores at 24 months, patients in the kyphoplasty arm maintained a statistically significant reduction in back pain scores relative to conservative therapy at 24 months (P = 0.009).40 A similar benefit was also reported at 36 months following kyphoplasty in a smaller prospective nonrandomized study of 60 patients.41 For height restoration, the results are less dramatic. Studies have shown that the magnitude of partial height restoration after vertebroplasty ranges from 2.5 to 8.4 mm and is overall similar to that reported after kyphoplasty.42 However, many of these studies did not report the incidence of fracture clefts. Overall, restoration of height appears to be related to dynamic mobility of fracture fragments from the presence of a fracture cleft.43 Dynamic mobility refers to a change in vertebral body height during changes in position, typically an increase in vertebral body height with supine or prone positioning versus the erect position; this typically occurs with fractures at the thoracolumbar junction (T11-L1), where the relatively fixed thoracic spine joins the more mobile lumbar spine. A study of 65 vertebral compression fractures referred for vertebroplasty revealed dynamic mobility in a third of treated levels.44 All fractures that were mobile had a fracture cleft, and all fractures that were fixed did not have a fracture cleft. Fractures that were mobile had an average absolute increase in anterior vertebral height of 8.4 mm (range, 2.0 to 17.4 mm) and a decreased kyphosis angle of 7.2 degrees (40%) after vertebroplasty. There was no restoration of height or correction of kyphosis in fixed fractures.44 In general, restoration of vertebral body height and correction of kyphosis may be desirable to improve postural endurance, reduce abdominal crowding, and improve overall pulmonary capacity. However, it remains unclear whether these results have any clinical significance.42

COMPLICATIONS ASSOCIATED WITH VERTEBRAL AUGMENTATION With adherence to careful technique and optimal visualization, the risk for morbidity or mortality from vertebral augmentation is low (Box 67.3). For treatment of benign osteoporotic fractures, complication rates are approximately 1%.31 Not surprisingly, they are higher for inexperienced practitioners or those attempting the procedure without

CHAPTER 67 — MINIMALLY INVASIVE PROCEDURES FOR VERTEBRAL COMPRESSION FRACTURES

Box 67.3 Potential Complications • Infection (osteomyelitis, epidural abscess) • P  araspinal hematoma • F  racture (of a rib, pedicle, or vertebral body) • F  ailure to improve pain or worsening of pain • P  neumothorax (for thoracic levels) • C  ement leakage • Nerve or spinal cord damage resulting in paralysis or bowel/bladder dysfunction • P  ulmonary embolism (secondary to cement or fat emboli) • H  ypotension or depressed myocardial function (secondary to free methylmethacrylate monomer or fat emboli) • D  eath from cardiovascular collapse or anaphylaxis to the cement

adequate image guidance or cement opacification.31 In the VERTOS II trial, the only complications referable to vertebroplasty that occurred in the 101 patients treated were a urinary tract infection in 1 patient and asymptomatic cement deposition into a segmental pulmonary artery in another.37 Similarly, in the FREE trial, complications referable to kyphoplasty in the 149 patients treated were one soft tissue hematoma and one urinary tract infection.39 Of note, almost all kyphoplasty procedures in the FREE trial were performed under general anesthesia, and in neither cohort were rates of urinary catheterization reported. In our experience, both vertebroplasty and kyphoplasty can be performed with local anesthesia and conscious sedation in most cases, and urinary catheterization is not required. The risks are greater in patients with malignancy-related fractures, with an overall complication rate of 5% to 10% being reported.45 In the CAFE trial, of the 70 patients treated with kyphoplasty for malignancy-related fractures, the only complications referable to kyphoplasty were one superficial wound infection and one patient with leakage of cement to the adjacent disk who had an adjacent fracture the day after the procedure.5 There were no serious adverse events that were deemed device related. Importantly, kyphoplasty was not performed on those who had vertebral fracture morphology deemed unsuitable as determined by the treating physician. Thus, patients with vertebra plana, comminuted fractures, fractures with posterior wall involvement, or those with epidural involvement, which would incur higher risk, were excluded. Extraosseous passage of cement is an important source of complications during vertebral augmentation. With vertebroplasty for osteoporotic fractures, small amounts of cement leakage are very common—in VERTOS II, 72% of treated vertebral bodies demonstrated cement leaks on postprocedure CT, with the majority being discal or into segmental veins; none extended into the spinal canal.37 All patients remained asymptomatic. There was one patient (1%) with an asymptomatic cement segmental pulmonary embolus.37 In performing kyphoplasty, a cavity is created and will fill first, which theoretically results in a lower rate of cement leakage.46-49 In the FREE trial, extravasation of cement occurred in 27% of treated vertebrae; however, this was assessed with intraoperative fluoroscopy and postoperative radiographs.39 Most were end-plate or discal leakages; there was one foraminal leakage, none extended into the spinal

931

canal, and no cement embolisms occurred. All patients remained asymptomatic.39 In a small retrospective series with postprocedure CT, the rate of local leakage of bone cement was 87.5% (21/24) with percutaneous vertebroplasty and 49.2% (29/59) with kyphoplasty.50 Cement leaks are also common with pathologic fractures.45,51,52 A recent retrospective study of CT-guided vertebroplasty for 331 malignant vertebral lesions revealed local cement leaks in 59 (194 of 331 vertebrae).53 Although osteolysis of the posterior wall was evident in 49% (162 of 331 vertebrae), only 5% (15 of 331) of leaks extended into the spinal canal through the posterior cortex. Pulmonary cement emboli were detected on 1 of 53 (2%) chest radiographs and 10 of 88 (11%) chest CT scans.53 A large single-center study of 106 patients with multiple myeloma treated by vertebroplasty revealed CT-detected extravasation of cement in 23% of the treated vertebrae, mainly into perivertebral (85%) and epidural (9%) veins. In five patients (5%), cement emboli were detected in the lungs. All leaks were asymptomatic.54 Although most extraosseous cement produces no symptoms or long-term morbidity, even small amounts of PMMA adjacent to a nerve root, including cement within the foraminal veins, can produce radicular pain.45 When radiculopathy is produced by cement leakage, the pain can be treated with a nerve root block or systemic steroids. The need for surgical decompression is rare,30 but it may be necessary when there is sufficient foraminal cement to cause frank root compression or when sufficient cement has been placed in the spinal canal to cause cord compression or cauda equina syndrome.26

POSTPROCEDURE AND FOLLOW-UP CARE AFTER VERTEBRAL AUGMENTATION Immediately following the procedure, manual compression is applied over the needle access sites for 5 minutes to promote clotting and prevent hematoma formation, which might increase postprocedure pain. Transfer to the stretcher using logroll precautions may be performed immediately after the procedure, except in the setting of a vertebral cleft, where we keep the patient prone on the fluoroscopy table for 15 to 20 minutes. The patient is kept supine and flat in bed for 2 hours, followed by a further hour with the head of the bed inclined 30 degrees after the procedure. To alleviate immediate postprocedure pain, the patient may be given 15 to 30 mg of intravenous ketorolac, unless renal insufficiency is present. Most patients can be discharged later the same day, although more fragile patients may be observed overnight in the hospital. Assessment of the patient shortly after the procedure commonly reveals improvement in the back pain. Frequently, the patient will be able to differentiate any new procedure-related pain, which is typically treated with nonsteroidal anti-inflammatory drugs and should resolve over a period of 24 to 72 hours. In the setting of clinical deterioration suggestive of cement leakage, crosssectional imaging should be performed. Postprocedure follow-up of the patient is important. The patient’s progress should be reviewed in the near term (e.g., 3 weeks) to assess pain and mobility levels and the need for analgesia. It is important to counsel the patient to report any sudden increase in back pain or new back pain because it may indicate a new fracture, and imaging should

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PART 7 — INTERVENTIONAL TECHNIQUES

be performed. Importantly, up to a third of patients will suffer a repeated fracture within 1 to 3 years, with the greatest risk in those with steroid-induced osteoporosis.55,56 Thus, prevention of future fractures is particularly important. Although the vast majority of recurrent fractures occur at new levels, a small percentage of patients suffer recurrent fracture at a previously treated level and may gain pain relief from repeated vertebral augmentation.57 This being said, caution should be taken when interpreting marrow edema at a previously treated level because according to one study, normal MRI findings following vertebroplasty include persistent or progressive marrow edema at the treated level in up to a third of patients and for up to 6 months after the procedure.58

KEY POINTS • Vertebral compression fractures are a common cause of pain and loss of independence in the middle-aged and elderly. • Vertebroplasty and kyphoplasty are minimally invasive, image-guided vertebral augmentation procedures that involve the injection of cement into a fractured vertebral body that fails conventional medical therapy. The primary goal of augmentation is pain relief and enhanced functional status with the secondary goals of vertebral body stabilization in cases of fracture. • Although two recent high-profile trials in the New England Journal of Medicine found no benefit with vertebroplasty, more recent randomized controlled trials of vertebral augmentation versus conservative therapy for both osteoporotic and malignant fractures have

KEY POINTS—cont’d demonstrated significant improvements in back pain, reduction in disability, and improvement in quality of life in favor of vertebral augmentation. • Complications are rare and generally result from unrecognized extraosseous leakage of the injected polymethyl methacrylate. Complications include radiculopathy, paralysis, and pulmonary embolism. These risks can be minimized and vertebral augmentation performed safely by experienced operators with the use of high-quality imaging, preferably with biplane fluoroscopy.

SUGGESTED READINGS Berenson J, Pflugmacher R, Jarzem P, et al. Balloon kyphoplasty versus non-surgical fracture management for treatment of painful vertebral body compression fractures in patients with cancer: a multicentre, randomised controlled trial. Lancet Oncol. 2011;12:225-235. Buchbinder R, Osborne RH, Ebeling PR, et al. A randomized trial of vertebroplasty for painful osteoporotic vertebral fractures. N Engl J Med. 2009;361:557-568. Kallmes DF, Comstock BA, Heagerty PJ, et al. A randomized trial of vertebroplasty for osteoporotic spinal fractures. N Engl J Med. 2009;361: 569-579. Klazen CA, Lohle PN, de Vries J, et al. Vertebroplasty versus conservative treatment in acute osteoporotic vertebral compression fractures (VERTOS II): an open-label randomised trial. Lancet. 2010;376: 1085-1092. Wardlaw D, Cummings SR, Van Meirhaeghe J, et al. Efficacy and safety of balloon kyphoplasty compared with non-surgical care for vertebral compression fracture (free): a randomised controlled trial. Lancet. 2009;373:1016-1024.

The references for this chapter can be found at www .expertconsult.com.

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