K y p h o p l a s t... C o m p r e s s i o...

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K y p h o p l a s t... C o m p r e s s i o...
Kyphoplasty in the Treatment of Osteolytic Vertebral
Compression Fractures as a Result of Multiple Myeloma
By S. Dudeney, I.H. Lieberman, M-K. Reinhardt, and M. Hussein
Purpose: We prospectively evaluated the safety and
efficacy of kyphoplasty in the treatment of osteolytic
vertebral compression fractures resulting from multiple
myeloma. The principle symptoms in multiple myeloma
result from bone destruction, especially the spine. Kyphoplasty is a new technique that involves the introduction of
inflatable bone tamps (IBT) into the vertebral body. The
purpose of the IBT is to restore the vertebral body back
toward its original height, while creating a cavity that can
be filled with highly viscous bone cement.
Patients and Methods: Fifty-five consecutive kyphoplasty procedures were performed in 18 patients with
osteolytic vertebral compression fractures resulting
from multiple myeloma. Cement leakage and any complications were recorded. Early objective analysis was
made by comparing preoperative and latest Short Form
36 Health Survey scores. Height restoration was estimated by measuring vertebral height on lateral
radiographs.
Results: The mean age of patients was 63.5 years,
mean duration of symptoms was 11 months, and mean
follow-up was 7.4 months. There were no major complications related directly to use of this technique. On
average, 34% of height lost at the time of fracture was
restored. Asymptomatic cement leakage occurred at
two (4%) of 55 levels. Significant improvement in SF36
scores occurred for Bodily Pain (23.2 to 55.4, P ⴝ
.0008), Physical Function (21.3 to 50.6, P ⴝ .0010),
Vitality (31.3 to 47.5, P ⴝ .010), and Social Functioning
(40.6 to 64.8, P ⴝ .014).
Conclusion: Kyphoplasty was efficacious in the treatment of osteolytic vertebral compression fractures resulting from multiple myeloma. Kyphoplasty is associated
with early clinical improvement of pain and function as
well as some restoration of vertebral body height.
J Clin Oncol 20:2382-2387. © 2002 by American
Society of Clinical Oncology.
ULTIPLE MYELOMA IS a tumor of B-cell origin.
Estimates of bone involvement at presentation vary
from 70% to 100% of patients. The principle morbidity in
the disease is as a result of skeletal involvement, particularly
the spine. Myeloma causes the resorption of bone by
stimulating osteoclasts via osteoclast-activating factors.1
The present treatments for multiple myeloma include radiotherapy and chemotherapy to control the disease and
bisphosphonates to deter bone destruction. Unfortunately,
multiple myeloma is presently still incurable; however,
survival rates are steadily improving.
Myelomatous osteolytic destruction of the spinal column
is common and has become more of a clinical issue with the
prolonged survival rates. Typically, the diffuse involvement
that occurs results in painful progressive vertebral compression fractures at multiple levels over time. Treatment with
bed rest, bracing, and analgesics are the standard of care for
most of these patients and have proven to be of limited
benefit, especially when considering the progressive spinal
kyphosis and its subsequent consequences.
Cement augmentation of the vertebral body has been used
for the relief of pain in the spine as a result of tumor
involvement since it was first described by Gallibert in
1984.2 This technique of vertebroplasty involves the injection of low-viscosity liquid bone cement (poly-methylmethacrylate [PMMA]) into the damaged vertebral body via
a percutaneous approach under image guidance. This technique has been shown to relieve pain in unstable vertebral
fractures caused by tumor and in osteoporotic compression
fractures. The difficulty with vertebroplasty as a technique
is two-fold. It makes no attempt to restore lost vertebral
height or correct the resultant spinal deformity. Deformity
becomes more important when there is generalized spinal
involvement as in multiple myeloma, with multiple
fractures occurring over time. The second major difficulty is the very high incidence of cement leakage as a
result of forcing liquid bone cement into the closed
collapsed space of the vertebral body. The rates of
cement leakage are reportedly from 30% to 60%.3-5
Neurologic compression after cement extravasation is a
rare but potentially devastating complication. Pulmonary
embolus of bone cement has also been reported.6,7 Open
surgical decompression in combination with vertebroplasty or surgically controlled vertebroplasty has been
advocated by some workers to overcome the difficulty of
M
From the Department of Orthopaedics and Minimally Invasive
Surgery Center, Cleveland Clinic Foundation; and the Multiple Myeloma Program, the Cleveland Clinic Tausig Cancer Center, Cleveland, OH.
Submitted September 21, 2001; accepted February 11, 2002.
Address reprint requests to I.H. Lieberman, MD, Department of
Orthopaedics, Minimally Invasive Surgery Center, 9500 Euclid Ave
Desk A-41, Cleveland, Ohio, 44195; email: [email protected].
© 2002 by American Society of Clinical Oncology.
0732-183X/02/2009-2382/$20.00
2382
Journal of Clinical Oncology, Vol 20, No 9 (May 1), 2002: pp 2382-2387
DOI: 10.1200/JCO.2002.09.097
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Copyright © 2002 American Society of Clinical Oncology. All rights reserved.
KYPHOPLASTY FOR MYELOMATOUS COMPRESSION FRACTURES
2383
leakage in vertebroplasty.8 This approach, however, defeats the purpose of a minimally invasive technique.
Kyphoplasty is a relatively new technique for cement
augmentation of the vertebra. It involves the placement of a
trochar into the vertebral body posteriorly followed by the
hand drilling of a bone channel in the vertebral body. This
allows the passage of a balloon-like inflatable bone tamp
(IBT) into the vertebral body. The inflation of the IBT under
careful image guidance is designed to produce a cavity
within the vertebral body and to restore lost vertebral
height.9,10 The creation of the cavity within the vertebra is
critical because it allows the insertion of very viscous,
partially cured cement into the vertebral body. This is in
contrast to the liquid state of cement used in vertebroplasty.
The insertion of thick viscous cement into a preformed
cavity has been shown to result in a lower rate of cement
extravasation in patients with osteoporotic vertebral compression fractures.11
The aim of this study was to determine the safety and
efficacy of the kyphoplasty procedure in patients with
vertebral compression fractures secondary to multiple myeloma. Furthermore, we aimed to examine the rates of
cement leakage, to look for evidence of height restoration
and to compare preoperative and early postoperative pain
and functional ability in treated patients.
of biplanar fluoroscopy. This is followed by placement of a cannulated
obturator over the guide wire. The obturator is then tapped into the
bone over the guide wire. A working cannula is placed over the
obturator and advanced until the tip of the cannula is seated in the
posterior portion of the vertebral body. A hand mounted drill bit is then
used to ream a tunnel in bone for the IBT to be passed through. The IBT
is ideally situated under the collapsed endplate on the lateral radiograph. Inflation is slowly performed under fluoroscopy, as are all stages
of guide wire, obturator, and cannula placement. The IBT inflation
pressure is monitored closely during inflation via an in-line pressure
gauge. Inflation is continued up to a maximum pressure of 220 psi or
until the vertebral compression fracture has been reduced. Inflation
should also be stopped if the balloon abuts the anterior, posterior, or
side wall of the vertebral body. When a suitable cavity has been
prepared and as much reduction is achieved as is possible, the PMMA
cement augmented with barium is mixed. Smaller bone cement
cannulae, which fit inside the working cannula, are prefilled with
cement. Before its application, the cement is allowed to thicken. A
2-cubic cm bolus of cement is repeatedly suspended from a wooden
spatula, and when the viscosity is such that the cement does not fall
from the spatula, it is ready for injection. A 0.5 mL portion of cement
is placed onto the drapes near the wound, and the radio opacity of the
cement is confirmed before injection of material into the vertebral
body. The bone filler cannula is then advanced through the working
cannula to the anterior vertebral body wall, and cement is slowly
extruded using a stainless steel stylet, which acts as a plunger. Filling
is performed under continuous lateral fluoroscopic guidance. The use of
the stylet and bone filler cannula enables cement to be applied at
considerably higher viscosity than possible with injection through a
5-mL syringe and 11-gauge needle. Cement filling is stopped when the
cement mantle reaches two thirds of the way back to the posterior
vertebral body cortex on the lateral fluoroscopic images. The number of
bone filler cannulae that need to be prepared is estimated from the final
inflation volume achieved with the IBT. Often the volume applied is 1
to 2 mL greater than the final inflation volume, allowing cement from
the central bolus to interdigitate with the surrounding cancellous bone
(Figs 1 and 2).
PATIENTS AND METHODS
This study was designed as a single cohort using consecutive
prospectively gathered data examining cement leakage, radiographic
vertebral height restoration, and early outcome in patients with multiple
myeloma after kyphoplasty as a treatment for osteolytic painful
progressive vertebral compression fractures.
Patients
Measurement of Height Restored:
Radiographic Assessment
Fifty-five consecutive kyphoplasty procedures were performed in 18
patients with vertebral compression fractures resulting from multiple
myeloma over 27 sessions. The mean age was 63.5 years (range, 48 to
79 years). The indications for kyphoplasty were vertebral compression
fractures caused by myelomatous destruction causing pain and unresponsive to nonoperative modalities. Vertebral fractures that were
unstable (by virtue of myelomatous destruction of the posterior
elements ie, pedicles and facets, along with the vertebral body) or with
retropulsed tissue or bone fragments were not considered for treatment
with this technique. The mean duration of symptoms was 11 months
(range, 0.5 to 24 months). Symptomatic levels were identified by
correlating the clinical data with magnetic resonance imaging findings
of marrow signal changes consistent with compression fractures.
Magnetic resonance imaging was used to confirm the presence of a true
wedge compression fracture and rule out burst type injuries with
retropulsed bone.
The vertical height of all fractured vertebrae were measured both
pre- and postoperatively. Vertebral height was defined as the distance,
endplate to endplate, at the center of the vertebral body on the lateral
radiograph. The vertical height of the vertebra above the fractured
vertebra was also measured to give an estimate of the height of the
fractured vertebra before fracture. Calculations were made as follows:
height regained ⫽ (posttreatment height ⫺ pretreatment fractured
height); height lost ⫽ (estimated prefracture height ⫺ pretreatment
fractured height); and the percentage of height lost that is now restored
⫽ (height regained/height lost) ⫻ 100. Multiple radiographs were
standardized for magnification by measuring and comparing known
landmarks to determine a magnification multiplier. The absolute values
in height (mm) before and after treatment were statistically compared
using paired nonparametric analysis (Wilcoxon signed rank test).
Repeat measurements of the same vertebral levels after a 2-week
interval with the same observer demonstrated an error of ⫾ 1.1 mm.
Kyphoplasty Technique
Assessment of Cement Leakage
IBT placement involves identifying an extrapedicular or transpedicular entry point into the vertebral body using a guide pin, with the use
Cement leakage was recorded prospectively at surgery. Postoperative radiographs were also examined for the presence of leakage of
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2384
DUDENEY ET AL
Fig 1. Steps in the kyphoplasty procedure (a) cannulation of the vertebral body; (b) placement of the IBT; (c) inflation of IBT and restoration of vertebral body
height; and (d) resultant cavity and cement fill.
cement. Cement leakage was recorded on the basis of position and
correlated with any postoperative clinical symptoms.
Measurement of Early Outcome: Clinical Assessment
Outcome data was obtained by comparing preoperative and latest
postoperative Short Form 36 Health Survey (SF36)12 data available at
the time of analysis. Bodily Pain, Physical Function, Vitality, and the
Social Function scores were selected from the SF36 profile before the
study as they were deemed the most relevant with regard to the
treatment of vertebral fractures in this population. Patients completed
the SF36 questionnaire without assistance if feasible at the time of their
preoperative assessment and at subsequent follow-up appointments at
1, 6, 12, 36, and 52 weeks. The Wilcoxon signed rank test was used for
statistical analysis of SF36 data. A P value of less than .05 was deemed
significant.
RESULTS
Patients and Levels
All 18 patients tolerated the procedure well. The 55 levels
treated ranged from T6 to L5, with the majority of treated
levels at the thoracolumbar junction (T11, n ⫽ 9; T12, n ⫽
7; L1, n ⫽ 8; and L2, n ⫽ 7). Twenty-seven percent of
levels were at T12 or L1. Postoperatively, all patients were
admitted to the 23-hour stay unit. Thirteen patients were
discharged home the following morning; 11 were discharged that same afternoon. Three patients stayed for 2 or
more days, all for medical/oncologic reasons unrelated to
the kyphoplasty procedure.
Safety and Efficacy
At final follow-up, there were no major complications
related directly to use of this technique, the IBT, or the use
of PMMA bone cement. There were no injuries to spinal
or extraspinal tissues as a result of guide pin, obturator,
or cannula placement. IBT expansion was bounded by the
vertebral body, and a cavity was created successfully in
all cases.
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2385
KYPHOPLASTY FOR MYELOMATOUS COMPRESSION FRACTURES
Fig 2. Clinical example of kyphoplasty for myeloma; (a) collapsing vertebral body; (b) IBT restoration of vertebral height and anterior wall alignment; (c)
and final cement augmentation.
Cement Extravasation
Cement extravasation was seen at two (4%) of 55 levels.
A small volume of cement entered the epidural space in one
patient. As soon as this was seen on the fluoroscope, cement
application was stopped. In the second patient, a small tail
of cement seeped through a sidewall cortical crack. No
problems were identified clinically as a result of these
extravasations postoperatively or at final follow-up.
Height Restored
Because of the nature of the osteolysis and resulting poor
radiographs, height measurements were only possible in 39
of the 55 levels treated. In those measured, the mean central
vertebral height lost was 7 mm (range, 2 to 17 mm). In
seven levels (18%), there was minimal loss of height (ⱖ 2
mm) before treatment. In all 39 levels, the mean percentage
of height lost that was restored by the procedure was 34%
(range, 0% to 100%). In 12 levels (31%), there was no
appreciable height restoration; at four levels, complete
restoration occurred. In the remaining 23 levels (60%), there
was a mean height restoration of 56%.
SF36 Evaluation
At a mean follow-up of 7.4 months, the SF36 scores for
Bodily Pain, Physical Function, Vitality, and Social Functioning all showed significant improvement. Bodily Pain
scores improved from 23.2 to 55.4 (P ⫽ .0008). Physical
function improved from 21.3 to 50.6 (P ⫽ .0010). Vitality
scores improved from 31.3 to 47.5 (P ⫽ .012). Social
Functioning improved from 40.6 to 64.8 (P ⫽ .014).
General Health, Mental Health, Role Physical, and Role
Emotional scores did not show significant improvement.
DISCUSSION
In this phase I study, kyphoplasty was found to be safe
and effective in the treatment of painful progressive osteolytic vertebral compression fractures resulting from myelo-
matous destruction. Kyphoplasty resulted in a marked
lowering in the leakage rate of cement compared with
previous techniques involving cement augmentation of
the vertebral body. On average, without stratifying for
chronicity or configuration of fracture, we restored 34%
of height lost at the time of fracture. In the vertebral
bodies where height was restored, we restored on average
56% of height lost.
We have previously examined the safety and efficacy of
the kyphoplasty procedure for the treatment of vertebral
compression fractures secondary to osteoporosis.11 In that
cohort, we found a similarly low rate of cement leakage, a
mean height restoration of 48%, and statistically significant
improvements in early postoperative SF36 pain and function scores.
Previous analysis of vertebroplasty has shown effective
pain relief. In this current cohort, we found statistically
significant improvement in bodily pain as measured by the
SF36 (prekyphoplasty ⫽ 23.2, postkyphoplasty ⫽ 55.4, P
⫽ .0008). Every patient in this group recorded a sustained
improvement in pain scores. These encouraging results are
in contrast to more recent vertebroplasty reports that show
at best a 50% improvement in pain scores in metastatic or
myeloma patients13
Cortet et al14 performed vertebroplasty in 37 patients, 29
with metastases and eight with multiple myeloma. They
achieved excellent pain relief but had a 72.5% leakage rate,
with two patients requiring surgical nerve root decompression.14 Cotten et al15 examined vertebroplasty in a similar
group of patients to show that pain relief was not related to
percentage filling. It has been reported that between 4 to 8 mL
of bone cement is estimated as the volume required to restore
strength and stiffness in vertebroplasty.16 This is difficult to
achieve with the vertebroplasty technique as evidenced by the
significant risk of cement leakage. Symmetrical cement placement has also been suggested to be of importance.17
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2386
DUDENEY ET AL
The short coming of this analysis is in the calculation and
reporting of height restored. We have used a simple reproducible method that we have used in previous studies.11 In
these myeloma patients, however, it can be difficult to fully
differentiate the effects of bone osteolysis caused by tumor
versus osteoporosis caused by medications and inactivity. In
our previous study, we documented an intraobserver error of
⫾ 1.1 mm. We did document, on average, a 34% restoration
of vertebral body height restoration, which is less than that
documented in the osteoporotic group (48%). This analysis
did not take into account chronicity of collapse or fracture
configuration. It is our belief that the osteolysis caused by
myeloma results in typically different fracture configurations (usually biconcave fractures) than those seen in true
osteoporotic patients (usually wedge compression).
Improving therapy and supportive care for myeloma and
the probable increase in overall survival18,19 makes effective skeletal care of ever-increasing importance. Even
though bisphosphonates have resulted in a significant decrease of skeletal morbidity,19 skeletal damage already
sustained at the time of diagnosis as well as the pain
resulting from these events limits mobility and, thus, increases morbidity and possibly mortality.
The specific advantages of kyphoplasty are that it makes
cement augmentation of the vertebrae a safer procedure and
provides the opportunity for some restoration in height. The
importance of cement leakage cannot be over emphasized. We advocate the use of biplanar fluoroscopy, with
continuous screening during actual insertion of cement,
and not computed tomography scanning as used by some
workers for vertebroplasty.
As with any new treatment, the main disadvantage is cost.
The cost of kyphoplasty treatment may be offset by the
decrease in morbidity, hospital stay, and pain management
efforts related to spinal disease in myeloma patients. Kyphoplasty needs to be studied with a prospective economic
evaluation of both treatment paths.
Multiple myeloma is grossly a very soft vascular tumor,
as evidenced by the backflow of blood from the working
cannulae during kyphoplasty. The near fluid consistency of
the tumor makes it easy for thick cement to displace it and
results in impressive cement filling of the vertebra. The
effects of dissemination of what is an already widespread
disease is not known. We do not suspect any significant
systemic effects and have not noted any in this initial group.
We were also able to proceed safely with the kyphoplasty in
all patients simultaneously with any chemotherapy, provided their WBC count was adequate and coagulation
profile was normal.
In other fracture types where the posterior wall is deficient, kyphoplasty is presently deemed unsuitable because
of the risk of further displacement of bone fragments by the
inflation of the balloon. Vertebroplasty has been used in
these cases with some success in the past. In these instances,
if open reconstruction is not considered appropriate, this
may be an indication to consider vertebroplasty.
Cement augmentation (vertebroplasty) has been used to
treat other tumors including lung adenocarcinoma,20 multiple eosinophilic granuloma,21 and vertebral hemangioma.2,22 Kyphoplasty may have a role in the safe treatment of
other disseminated lytic tumor types, and this is currently
under investigation.
Probably the most significant clinical issue when considering treatment for myeloma patients is the increasing
survival time associated with improvements in chemotherapy. Nonetheless, by definition, all patients with multiple
myeloma present with bone marrow involvement. The
majority of morbidity and mortality is caused by skeletal
failure because of bone destruction. Therefore, timely intervention of effective skeletal reconstruction is of everincreasing importance. Because we have gained experience
with the technique and have witnessed the early and
sustained clinical improvement in pain and function, we
now advocate early treatment of any fractured or collapsing
vertebral body. This philosophy should avoid the structural
and debilitating functional effects of a progressive spinal
kyphotic alignment.
ACKNOWLEDGMENT
We thank Kyphon Inc, Sunnyvale, CA, for providing the equipment
and technical support for this study.
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KYPHOPLASTY FOR MYELOMATOUS COMPRESSION FRACTURES
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