SPINE TRAUMA IN THE ELDERLY

Management of the Elderly With Vertebral

Compression Fractures
Christina L. Goldstein, MD,
FRCSC*
Norman B. Chutkan, MD
Theodore J. Choma, MD*
R. Douglas Orr, MD, FRCSC
*Department of Orthopaedic Surgery,
University of Missouri, Columbia, Missouri;
The Center for Orthopedic Research and
Education, Phoenix, Arizona; Cleveland
Clinic, Richard E. Jacobs Health Center,
Cleveland, Ohio
Correspondence:
Christina L. Goldstein, MD, FRCSC,
Department of Orthopaedic Surgery,
Missouri Orthopaedic Institute,
University of Missouri,
1100 Virginia Ave.,
Columbia, MO 65212.
E-mail: goldsteincl@health.missouri.edu
Copyright 2015 by the
Congress of Neurological Surgeons.
Vertebral compression fractures (VCFs) are the most common type of fracture sec-
ondary to osteoporosis. These fractures are associated with significant rates of mor-
bidity and mortality and annual direct medical expenditures of more than $1 billion in
the United States. Although many patients will respond favorably to nonsurgical care of
their VCF, contemporary natural history data suggest that more than 40% of patients
may fail to achieve significant pain relief within 12 months of symptom onset. As
a result, percutaneous vertebral augmentation is often used to hasten symptom reso-
lution and return of function. However, controversy regarding the role of kyphoplasty
and vertebroplasty in the treatment of symptomatic VCFs exists. The purposes of this
review are (1) to outline the epidemiology of VCFs as well as the physical morbidity and
economic impact of these injuries, (2) to familiarize the reader with the best available
evidence surrounding the operative and nonoperative treatment of VCFs, and (3) to
examine the literature pertaining to the cost-effectiveness of surgical management of
VCFs with the overarching goal of helping physicians make informed decisions
regarding symptomatic VCF treatment.
KEY WORDS: Elderly, Kyphoplasty, Nonoperative management, Osteoporosis, Vertebral compression fracture,
Vertebroplasty
Neurosurgery 77:S33S45, 2015 DOI: 10.1227/NEU.0000000000000947 www.neurosurgery-online.com

Epidemiology between the time periods of 1989 to 1991 and

V
ertebral compression fractures (VCFs) are
the most common type of osteoporotic
fracture, accounting for almost as many
fractures as hip and distal radius fractures com-
bined.1 Prevalence is both sex and age specific,
with VCFs affecting 25% of postmenopausal
women older than 50 years of age and 40% by
80 years of age.2-4 Worldwide, a new VCF
occurs every 22 seconds.5 In a 2010 study, the
prevalence of VCFs ranged between 30% and
50% in adults older than 50 years of age,5 with
a 47% increase in vertebral fractures occurring
ABBREVIATIONS: AE, adverse event; CI, confi-
dence interval; KP, kyphoplasty; HRQOL, health-
related quality of life; INVEST, Investigational
Vertebroplasty Safety and Efficacy Trial; MD, mean
difference; ODI, Oswestry Disability Index; QUALEFFO,
Quality of Life Questionnaire of the European Foun-
dation for Osteoporosis; RCT, randomized, controlled
trial; RMDQ, Roland-Morris Disability Questionnaire;
SF-36, Short Form 36; VCF, vertebral compression
fracture; VP, vertebroplasty
2009 to 2011.2 Recent estimates have placed the
American annual incidence of VCFs close to 1.5
million.6
Although not all patients with a VCF will
seek medical attention, these fractures result in
150 000 hospital admissions7 and more than
160 000 outpatient physician visits per year in
the United States.8 More than 40% of patients
will fail to achieve significant pain relief by
12 months.9 Reflective of the well-recognized
complications associated with nonsurgical
management of VCFs, between 1993 and
2004, the rates of percutaneous treatment of
VCFs increased 12 900%, from 182 in 1993
to more than 23 000 in 2004.10 Use of percu-
taneous vertebral augmentation declined after
the publication of 2 double-blind, randomized,
controlled trials (RCTs) in 2009,11,12 but
annual rates of vertebroplasty (VP) and kypho-
plasty (KP) remain high13,14 and will likely
continue to do so as the number of patients
with symptomatic VCFs continues to increase
in coming decades.

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GOLDSTEIN ET AL
Morbidity and Mortality of VCFs
VCFs are associated with progressive loss of height, spinal
kyphosis, pain, reduced mobility and independence, and psycho-
logical distress.15 Not surprisingly, these impacts lead to
a significant decrease in patient-reported health-related quality
of life (HRQOL) and loss of quality-adjusted life years.16-18
Having had a VCF also places a patient at increased risk of
experiencing another osteoporotic fracture, both in the spine and
elsewhere. One of every 5 women with a VCF will experience
a second VCF in the next 12 months, while the risk of
nonvertebral osteoporotic fractures, including those of the hip,
increases 2 to 3 times.5 Of even greater concern is the observation
that long-term mortality in patients with a history of VCF is
significantly higher than that observed in the general population,
paralleling mortality rates associated with osteoporotic hip
fractures.5
Multiple studies published over the past decade have provided
insight into the population-level morbidity associated with VCFs
in the United States (Table 1), including large reviews of the
Nationwide Inpatient Sample,13,19 reviews of data from the
Centers for Medicare and Medicaid Services,20,21 and data from
the American College of Surgeons National Surgical Quality
Improvement Program database.22 These investigations have
identified significant rates of deep vein thrombosis (0.7%-6.6%),
pulmonary embolism (0.4%-1.9%), pneumonia (3.1%-13.0%),
cardiac complications (0.4%-0.5%), decubitus ulcers (1.1%-
4.4%), and postoperative infections (0.1%-0.15%), regardless of
treatment type. Discharge to a skilled nursing or other facility
occurs in 33.5% to 60% of patients, and 30-day readmission
rates after VCF irrespective of treatment method range from
10.8% to 61.9%. Finally, in-hospital mortality rates for patients
with a VCF range from 0.3% to 1.7%, with rates increasing at 1
year to 5.2% to 26.9%. Mortality rates were consistently shown
to be lower in the augmented patients than in those receiving
nonoperative treatment,19-21 with KP demonstrating lower
mortality rates than VP.13,20 This latter phenomenon may be
partially explained by higher rates of major medical comorbidities
in patients undergoing VP vs KP.13
Economic Burden of VCFs
In addition to the significant medical morbidity and mortality
associated with VCFs, the financial burden of these fractures is
also a major public health concern. In 2002, Tosteson and
Hammond23 estimated the annual direct medical costs of
osteoporotic fractures in the United States to be $12.2 billion
to $17.9 billion. Costs attributable specifically to VCFs have been
appraised at more than $1.07 billion.1 In addition, the indirect
costs due to patient and caregiver loss of productivity have been
estimated at $6 billion annually.24
Although some may argue that these enormous health care costs
are associated with expensive, clinically unproven surgical inter-
vention, this is not necessarily the case, as nonoperative manage-
ment of VCFs is also associated with significant direct and indirect
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health care costs due to the loss of independence and to
complications. In a review of the Medicare population, 2006 total
mean charges to Medicare for inpatient treatment of VCFs was
more than $1.8 billion, 45% of which was for nonoperative care.20
Similar results were found in the 2005 Nationwide Inpatient
Sample; during that period alone, US$98 223 030 were spent on
nonoperative management of VCFs, almost 75% of the total
costs observed in this study.19
As rates of osteoporosis in the United States are expected to
increase by 50% by the year 2025,1 there is no doubt that the
psychological, physical, and economic burden associated with
osteoporotic VCFs will continue to grow.
TREATMENT OF VCFs
Nonoperative Treatment
Osteoporotic VCFs manifest a wide range of symptoms, with
some patients remaining asymptomatic, whereas others report
severe, incapacitating pain. Of the symptomatic patients, a subset
will report significant improvement in pain and function within
days to weeks with supportive, conservative management, whereas
others will remain symptomatic for a prolonged period of time.
The goals of nonoperative management are pain control, early
mobilization, prevention of deformity, and functional restoration.
Initial management usually begins with narcotic analgesics as
tolerated, immobilization with an external orthosis, and the
administration of nasal calcitonin, which, in addition to its
antiresorptive effect, has an analgesic effect as well. Narcotic
medication, although useful in controlling pain, may have signif-
icant side effects in the elderly, including constipation, confusion,
and respiratory depression. The external orthosis most commonly
used to prevent kyphotic deformity is a Jewitt-type hyperextension
brace. These braces are often poorly tolerated in the elderly, and
their utility may be limited by body habitus. In a comparative study
of patients managed with a soft brace, a rigid brace, or no brace, no
significant difference in outcome was seen between the 3 groups.25
Nonoperative treatment is usually continued until the acute pain
has subsided, adequate mobilization is achieved, and absence of
progressive deformity is confirmed. Despite the large number of
osteoporotic VCFs that occur each year, there is a paucity of data
and studies evaluating nonoperative management of these patients.
In a meta-analysis of studies related to conservative management of
osteoporotic compression fractures, the quality of data was rated as
low to very low.26
In addition to the lack of data related to the clinical outcome of
nonoperative management of osteoporotic VCFs, there is also
a lack of data regarding the cost-effectiveness of nonoperative
management. In a retrospective, propensity-matched comparison
of VP, KP, and nonsurgical management for the treatment of
VCFs in patients aged 18 years if age and older using data from the
Thomson Reuters MarketScan database including Commercial,
Medicare Supplemental, and Medicaid data from 2005 to 2009,
VP and KP were found to be significantly more costly at 1 year, but
at 2 and 4 years, no significant difference in cost was seen.27
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NEUROSURGERY

TABLE 1. Summary of Population-Level Studies Examining Morbidity and Mortality Associated With Vertebral Compression Fracturesa
No. of Patient Demographic Discharge
Study Database Queried Time Period Patients Characteristics Treatment (%) Destination (%) Morbidity (%) Mortality (%)
19
Zampini et al, NIS 2005 5766 Mean age, y, 81.1 71.3% Nonop: 84.7 Home: 23.7 Infection (all): 0.1 In-hospital
2010 female CCI, % KP: 15.3 Home with Pneumonia: 3.1-3.4 Nonop: 1.6
0: 36.7 HC: 12.2 DVT: 0.2 KP: 0.3
1: 29.5 SNF: 33.5 Decubitus ulcer: 1-1.1
2: 19.8 Other facility:
31: 14.0 45.3
Chen et al,20 Medicare provider 2006 68 752 Mean age, y: 81.9 76.8% Nonop: 55.6 Home: 37.9 Infection (postop): 0.1 In-hospital
2013 analysis and female CCI, % VP: 11.2 Home with Pneumonia: 3.14 Nonop: 1.72
review file 0: 31.8 KP: 33.2 HC: 14.8 DVT: 2.66 VP: 0.53
database 1: 28.2 SNF: 32.7 PE: 0.29 KP: 0.35
2: 17.0 Other facility: Decubitus ulcer: 0.95 1-y
31: 23.0 14.6 Nonop: 26.9
VP: 21.2
KP: 14.8
3-y
Non-op57.7
VP: 50.3
KP: 40.1
Goz et al,13 NIS 2005-2010 307 050 (VP/KP) VP: 26.7 Not reported (% VP/KP) In-hospital
2013 Mean age, y: 77.8/76.7 KPL 73.3 Infection (postop): VP: 0.93
Female: 74.5/73.2% 0.14/0.11 KP: 0.6
Diabetes: 8.13/18.0 Respiratory: 0.29/0.38
Lung disease: 25.5/24.7 DVT: 1.04/0.71
CAD: 20.2/20.2 PE: 0.72/0.42
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Renal disease: 8.25/6.33 Cardiac: 0.37/0.53

Cancer: 7.67/6.64 CNS: 0.1/0.13
McCullough CMS Outpatient 20% 126 392 (Nonop/augmented) Nonop: 91.7 Not reported Major medical (Nonop/

OSTEOPOROTIC VERTEBRAL COMPRESSION FRACTURES

et al,21 2013 billing and random Mean age, y: 80.2/80.0 VP/KP: 8.3 complications (nonop/ augmented)
Medicare sample Female: 77.5/78.2% augmented) 30 d: 1.5/0.4
Provider Analysis from 2002 Quan comorbidity score 30 d: 10.4/9.3 1 y: 6.7/5.2
and Review to 2006 0: 25.3/24.4 1 y: 28.9/28.9
claims 1: 24.1/23.9
2: 18.4/18.1
31: 32.2/33.7

(Continues)

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GOLDSTEIN ET AL

Operative Treatment

modified Charlson Comorbidity Index; CMS, Center for Medicare and Medicaid Services; CNS, central nervous system; CVA, cerebrovascular accident; DVT, deep vein thrombosis; HC, home care; KP, kyphoplasty;
MAE, minor adverse events; NIS, National Inpatient Sample; Non-op, non-operative treatment; PE, pulmonary embolism; SAE, serious adverse events; SNF, skilled nursing facility; UTI, urinary tract infection;
ACS-NSQIP, American College of Surgeons National Surgical Quality Improvement Program; ARF, acute renal failure; ASA, American Society of Anesthesiologists; CAD, coronary artery disease; CCI, Deyo-
Historically, surgical intervention in patients with osteoporosis
Mortality (%)

Total: 1.5 was reserved for patients with neurological deficits or gross
instability because of the significant complication rate associated
with open surgical procedures in this patient population. The
30 d

introduction of percutaneous vertebral augmentation procedures

such as KP and VP has resulted in a major paradigm shift in the
management of these patients.
In VP, cement is injected percutaneously into the fractured
Pneumonia: 0.5
Morbidity (%)

Stroke/CVA: 0.1

vertebrae without an attempt at vertebral expansion, whereas in

DVT/PE: 1.2
Sepsis: 0.2

KP, a balloon is introduced and inflated in an attempt to restore

ARF: 0.4

UTI: 1.9
MAE: 3.7

vertebral height and create a cavity that is then filled with bone
SAE: 6.6

cement (Figure). Surgical intervention has become quite common

and widespread, and there is now controversy about the
appropriate duration of nonoperative management before offer-
Treatment (%) Destination (%)

ing surgical intervention, with some surgeons advocating early

Facility: 19.8
Discharge

operative intervention and others advocating an initial trial of

Home: 80.2

nonoperative management.28 However, enthusiasm for vertebral

augmentation may be dampened by concerns regarding compli-
cations such as adjacent segment fracture, venous embolization of
cement, and cement extravasation resulting in neurological
injury.
KP: 89.6
VP: 10.4

VP vs Sham
In the August 2009 issue of the New England Journal of
Patient Demographic

Medicine, 2 sham-controlled, RCTs examining the efficacy of VP

Female, 70.8% ASA
Characteristics

for the treatment of osteoporotic VCFs were published, the

Mean age, y: 78.9

INVEST (Investigational Vertebroplasty Safety and Efficacy

1: 2: 22.7%

Trial)12 and A Randomized Trial of Vertebroplasty for Painful

3: 66.7%
4: 10.6%

Osteoporotic Vertebral Fractures.11 All patients had needles

introduced, and the periosteum was infiltrated with a local
anesthetic, with cement also being injected in the operative
group. In both studies, there was no difference in the control and
Patients

treatment groups in any primary or secondary outcome. One-

No. of

850

year follow-up from the INVEST demonstrated a small but

statistically significantly greater improvement in pain in the VP
group compared with the sham group (1.02 points; 95%
Time Period

confidence interval [CI]: 0.04-2.01; P = .04).29 On the surface,

2011-2012

the results from these sham-controlled studies suggest that

a placebo effect of an operative intervention accounts for the
difference between groups treated with surgery and those
Database Queried

managed with conventional medical therapy. However, meth-

odological flaws have been identified in both primary studies, and
the results have been called into question.30-32
Toy et al,22 2014 ACS-NSQIP

Criticisms of the trials have included the inclusion of chronic

fractures (up to 12 months), lack of clarity regarding acute
TABLE 1. Continued

fracture definitions, lack of a true sham procedure due to

injection of a local anesthetic agent, recruitment difficulty
VP, vertebroplasty.

necessitating repowering during enrollment reductions in

sample size, disproportionately high recruitment from a single
site, and refusal of randomization by more than 60% of eligible
Study

subjects. In support of the possibility of these studies being

underpowered was the finding in the Kallmes et al12 trial of
a

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 OSTEOPOROTIC VERTEBRAL COMPRESSION FRACTURES

FIGURE. A 66-year-old woman with a bone mineral density T-score of 24.7 presented with a 6-month history of back pain after a minor trauma. Lateral radiographs
demonstrated T7 and T9 vertebral compression fractures (A). Sagittal short tau inversion recovery magnetic resonance images showed increased signal intensity at the 2 levels
indicating nonunion (B). The patient was taken for balloon kyphoplasty of both fractures using a bilateral technique (C and D). Postoperative radiographs demonstrated good
cement fill of the fractured vertebrae with no cement leakage (E). Four weeks postoperatively, the patient reported a 5-point decrease in visual analog scale back pain score and
improved functional tolerance.

a trend toward a higher percentage of patients undergoing VP
achieving a clinically meaningful improvement in pain, defined
as a 30% decrease in baseline (64% vs 48%, P = .06). This
would suggest the possibility of a b error, rejecting the null
hypothesis where a true effect exists due to low numbers.
VP vs Nonoperative Care
Between 2007 and 2014, 6 RCTs comparing VP with
nonoperative care were published.33-38 In the earliest trial of
treatment for subacute or chronic painful osteoporotic VCFs, the
VERTOS study, Voormolen et al38 randomized 18 patients 50
years of age or older to VP and 16 to medical management. After
2 weeks, 88% of the nonoperative cohort was permitted to cross
over to the VP arm. Two weeks after surgical treatment, there was
a trend toward greater pain improvement in the VP group that
was not statistically significant, and only patients undergoing VP
demonstrated an improvement in HRQOL as measured by the
Roland-Morris Disability Questionnaire (RMDQ).
In 2009, Rousing et al37 published a second RCT of VP vs
conservative treatment in 50 Danish patients 65 years of age or
older with acute (,2 weeks) or subacute (2-8 weeks) osteoporotic
VCFs. At 3-month follow-up, no significant difference was
observed between the operative and nonoperative cohorts with
regard to visual analog scale (VAS) score for back pain or Short
Form 36 (SF-36) score. Patients undergoing VP did demon-
strate better scores on the EQ-5D, although significant baseline
differences in EQ-5D scores existed between the treatment
arms despite randomization. Failure to observe a difference in
the treatment effects between these 2 groups may have been
due to a lack of statistical power or inclusion of patients with
acute fractures that may be more likely to improve with
conservative care.
Subsequently, VERTOS II, a second Dutch randomized
comparison of VP vs conservative treatment in acute (,6 weeks)
osteoporotic VCFs, was published.36 VP was performed in 101
patients 50 years of age and older referred for spine radiographs to
investigate back pain, whereas another 101 received nonoperative
treatment. At 1 year, the decrease in VAS score was significantly
greater in patients treated with VP, and they also demonstrated
greater and faster improvement in HRQOL on the RMDQ and
Quality of Life Questionnaire of the European Foundation for
Osteoporosis (QUALEFFO).
In 2011, Farrokhi et al35 reported on 82 subjects with 4
months to 1 year of refractory pain from an osteoporotic VCF
randomized to VP (n = 40) or optimal medical therapy (n = 42).
At 6-month follow-up, patients in the VP group reported
significantly less pain than those in the medical therapy group

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GOLDSTEIN ET AL
(VAS back pain score, 2.2 6 2.1 vs 4.1 6 1.5, P , .02);
however, similar to other studies, this difference was not
maintained at 12-, 24- or 36-month follow-up. In contrast,
HRQOL as measured by the Oswestry Disability Index (ODI)
was significantly better in the VP group immediately after surgery
and at the final 36-month follow-up compared with the medically
treated group (30.1 6 3.0 vs 44.0 6 2.5, P , .03 and 8.0 6 1.7
vs 22.0 6 1.2, P , .01, respectively).
The next year, Blasco et al33 reported on their prospective,
single-center RCT of 125 patients comparing VP (n = 64) with
conservative treatment (n = 61). Included patients had to have
had symptoms for less than 12 months with a radiographically
confirmed VCF demonstrating edema on magnetic resonance
short tau inversion recovery images or increased activity on bone
scanning. Significantly greater improvement in VAS scores at
2-month follow-up in the VP group (42% vs 25%) with earlier
improvement in QUALEFFO scores was observed. However,
residual back pain was similar in the 2 treatment groups at
12-month follow-up, with no significant differences in total
QUALEFFO score or analgesic use at this time point.
Most recently, Chen et al34 published the results of their single-
center, randomized study of VP (n = 46) vs nonoperative
treatment (n = 50) in patients with 1 or more osteoporotic
compression fractures identified by high signal on T2-weighted
magnetic resonance imaging and at least 3 months of unremitting
pain. Patients were allowed to cross over into the VP arm after 3
months of conservative care, with 4 patients selecting this
treatment option. At the final 1-year follow-up, both groups
had demonstrated improvements in VAS score for back pain and
disability and HRQOL as measured by the ODI and RMDQ.
However, significantly greater improvements were observed in
the VP group compared with the nonoperative group (VAS score
for back pain, 4.0 vs 2.3). This divergence of treatment effects
was observed as early as 1 week after treatment initiation and was
maintained throughout the study period.
KP vs Nonoperative Care
The FREE (Fracture Reduction Evaluation) trial is the only
large-scale RCT of percutaneous balloon KP (n = 149) vs
nonoperative treatment (151) for acute symptomatic VCFs,
although 2 patients with multiple myeloma or metastatic
osteolytic lesions were included in each group.39 Fractures were
a mean of 5.6 weeks and 6.4 weeks old in the KP and nonsurgical
groups, respectively. At 1-month follow-up, the mean SF-36
Physical Component Summary score improvement was 5.2
points greater in the KP group than in the nonsurgical group
(95% CI: 2.9-7.4, P , .0001). This difference decreased to 1.5
points (95% CI: 20.8 to 3.9, P = .21) at 12-month follow-up.
The KP group also demonstrated greater improvements in EQ-
5D quality of life scores at 1 and 12 months (0.18, P = .0003 and
0.12, P = .03, respectively). VAS back pain scores showed a 2.2-
point greater decrease in the KP group at 1 week (95% CI: 1.6-
2.8, P , .0001) and a 0.9-point greater decrease at 12 months
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(95% CI: 0.3-1.5, P = .003). These differences in back pain and
HRQOL favoring KP have subsequently been shown to be
maintained at 24 months.40
VP vs KP
Two RCTs comparing VP with KP for the symptomatic
treatment of VCFs and reporting pain or HRQOL outcomes
have been published since 2010, with the long-term results of 1
RCT having been recently reported.41 In the first head-to-head
comparison of the 2 techniques, Liu et al42 randomized 100
patients with an acute osteoporotic VCF of the thoracolumbar
junction (T12-L1) to VP (n = 50) or KP (n = 50). Although
both groups demonstrated improvement from baseline to the
final follow-up at 6 months (KP = 25.4, VP = 25.6), no
significant differences in VAS score for back pain improvement
were observed between the treatment arms. Disability and
HRQOL were not measured in this trial. These improvements
in back pain were subsequently reported as being durable at
5-year follow-up.41
More recently, Dohm et al43 performed a randomized trial of
patients with osteoporosis and 1 to 3 acute VCFs treated with KP
(n = 191) or VP (n = 190). Patients had to have concordant
clinical findings and either new (,6 months) vertebral height loss
on computed tomography, magnetic resonance imaging, or
radiography; edema on magnetic resonance imaging scans; or
increased uptake on a bone scan. Patients in both treatment arms
demonstrated statistically significant improvements in back pain,
SF-36 Physical Component Summary, EQ-5D, and ODI scores
at 24 months, with concomitant decreases in opioid use.
However, no significant difference in treatment outcome was
observed between KP and VP on any clinical outcome measure.
SYSTEMATIC REVIEWS AND META-ANALYSES
OF RCTs
As the rates of use of VP and KP for the management of
symptomatic VCFs have increased and as more RCTs examining
VCF treatment have been published, multiple investigators have
attempted to synthesize the literature regarding nonoperative and
operative management of VCFs by performing systematic reviews
and meta-analyses.44-53 As would be expected, the findings and
conclusions of the publications vary depending on the year of
publication, intervention, and control groups included and
methods of statistical analysis. A summary of selected findings
of published systematic reviews of RCTs examining the treatment
of osteoporotic VCFs and presenting at least 1 clinical outcome
(VAS score for back pain, disability, or HRQOL) is presented in
Table 2. For a comprehensive list of all trials included in each of
the meta-analyses, readers are directed to the primary references.
Impact on Back Pain
Four different meta-analyses compared improvements in back
pain between VP and nonoperative treatment.49,52-54 At 12
months, 3 studies reported mean differences between the 2
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NEUROSURGERY

TABLE 2. Summary of Meta-Analyses of RCTs of Treatment of Vertebral Compression Fracturesa

Databases Study Type and Patient
Study Queried Time Period Number Comparisons No. of Subjects Demographics Outcomes
Anderson MEDLINE January 1980 RCTs VP 1 KP vs VA = 538 Mean age, y: NR Pain reduction
et al,55 CDSR to 8 (6 included sham 1 nonop Nonop = 437 % Female: NR VP/KP vs nonop (MD 6 95% CI)
2013 CENTRAL July 2011 in meta- Early (2-12 wk): 0.73 6 0.38 (P , .001)
CINAHL analysis) Late (.12 wk): 0.58 6 0.39 (P , .001)
Embase Functional outcome (RMDQ or ODI)
VP/KP vs nonop (SMD 6 95% CI)
Early (2-12 wk): 1.08 6 0.75 (P , .05)
Late (.12 wk): 1.16 6 1.02 (P , .05)
HRQOL (QUALEFFO or EQ-5D)
VP/KP vs nonop (SMD 6 95% CI)
Early (2-12 wk): 0.39 6 0.23 (P , .05)
Late (.12 wk): 0.33 6 0.17 (P , .05)
Liu et al,49 MEDLINE January 1980 RCTs VP vs sham 1 VP = 291 Mean age, y Pain reduction
2013 CDSR to 5 nonop Nonop = 286 VP: 72-80 Total (MD 6 95% CI)
CCRCT December Nonop: 74-80 2 wk: 21.192 6 1.593 (P = .14)
CINAHL 2012 Female: 69.3%-80.3% 2-3 mo: 21.72 6 0.54 (P , .00001)
Embase .6 mo: 21.59 6 0.55 (P , .00001)
Buchbinder CENTRAL Database RCTs and quasi- VP vs sham VP vs sham = 209 Mean age, y Pain reduction (12 mo MD [95% CI])
et al,52 MEDLINE inception to RCTs VP vs nonop VP vs nonop = 566 VP vs sham VP vs sham: 20.5 (21.82 to 0.82)
2015 EMBASE November 12 (11 RCTs and VP vs KP VP vs KP = 545 VP: 73.4-74.2 VP vs nonop: 20.83 (21.55 to 20.11)
2014 1 quasi-RCT) Sham: 74.3-78.9 VP vs KP: 0.30 (20.40 to 1.00)
VP vs nonop Functional Outcome (RMDQ or ODI, MD [95% CI])
VP: 64.6-80 VP vs sham (1 mo RMDQ): 21.09 (22.94 to 0.76)
Nonop: 66.5-80 VP vs nonop (12 mo either): 21.26 (22.61 to 0.08)
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VP vs KP VP vs KP (12-mo ODI): 20.0 (0.0-0.0)

VP: 71.3-75.7 HRQOL (EQ-5D, MD [95% CI])

OSTEOPOROTIC VERTEBRAL COMPRESSION FRACTURES

KP: 63.3-80 VP vs sham (1 mo): 0.05 (0.01 to 0.11)
% Female VP vs nonop (12 mo): 0.07 (20.00 to 0.14)
VP vs sham VP vs KP: 20.0 (0.0-0.0)
VP: 77.9-81.6
Sham: 73.0-77.5
VP vs nonop
VP: 69.3-77.8
Nonop: 69.3-87.5
VP vs KP
VP: 60.0-76.0
KP: 70.0-87.5

(Continues)

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S40 | VOLUME 77 | NUMBER 4 | OCTOBER 2015 SUPPLEMENT

GOLDSTEIN ET AL
TABLE 2. Continued
Databases Study Type and Patient
Study Queried Time Period Number Comparisons No. of Subjects Demographics Outcomes
Chen et al,53 Amed Database RCTs VP vs nonop Nonop = 337 Mean age, y: NR Pain reduction (12 mo, MD [95% CI])
2015 BNI inception to 5 KP vs nonop VP = 241 % female: NR VP vs nonop: 21.81 (23.1 to 0.47)
Embase July 2014 VP vs KP KP = 199 KP vs nonop: 21.1 (21.4 to 0.89)
Ubmed VP vs KP: 0.15 (20.25 to 0.54)
CENTRAL
Google
Scholar
SIGLE
NTIS
NRR (UK)
CCTD
Guo et al,54 CENTRAL Database RCTs VP vs sham 1 VP or KP = 701 Mean age, y Pain reduction ($12 mo, MD 6 95% CI)
2015 PubMed inception to 11 nonop Sham or nonop = VP/KP: 64.8-80 VP vs nonop: 21.38 (22.64 to 20.12)
Embase June 2014 KP vs sham 1 700 Sham/nonop: 63-80 KP vs nonop: 20.69 (21.34 to 20.04)
Web of nonop % female: NR VP/KP vs sham/nonop: 21.24 (22.20 to 20.29)
Science HRQOL
CBMD RMDQ (,3 mo, MD 6 95% CI)
CNKI VP vs sham/nonop: 22.90 (24.34 to 21.45)
Wangfang KP vs sham/nonop: 25.99 (210.6 to 21.38)
VP/KP vs sham/nonop: 24.97 (28.71 to 21.23)
SF-36 ($12 mo, MD 6 95% CI)
VP vs sham/nonop: 1.20 (21.33 to 3.72)

a
BNI, British Nursing Index; CBMD, China Biology Medicine disc; CCTD, Current Controlled Trials Database; CDSR, Cochrane Database of Systematic Reviews; CENTRAL, Cochrane Central Register of Controlled
Trials; CI, confidence interval; CNKI, China National Knowledge Infrastructure; HRQOL, Health-Related Quality of Life; KP, kyphoplasty; MD, mean difference; NR, not reported; NRR(UK), National Research Register
(UK); NTIS, National Technical Information Service; ODI, Oswestry Disability Index; QUALEFFO, Quality of life Questionnaire of the European Foundation for Osteoporosis; RCTs, randomized, controlled trials;
RMDQ, Roland Morris Disability Questionnaire; SMD, standardized mean difference; VA, vertebral augmentation; VP, vertebroplasty.
www.neurosurgery-online.com

Copyright Congress of Neurological Surgeons. Unauthorized reproduction of this article is prohibited


treatment arms ranging from 0.69 to 1.75 in favor of VP.49,52,54 A
single study reported a standardized mean difference of 21.81
(95% CI: 23.1 to 0.47), also in favor of VP.53 Comparing VP
with sham surgery, 2 meta-analyses failed to identify a difference
in pain control at 12 months.49,52 This is possibly due to the
infiltration of local anesthetic at the time of the sham surgery or
a placebo effect of the sham surgical intervention.
Similar to the comparisons of VP with nonoperative treatment,
KP has also been shown to improve pain to a greater extent than
nonoperative modalities. At 12 months, Chen et al53 reported
a 1.1-point standard mean difference (MD) between KP and
nonoperative treatment in favor of surgery, whereas Guo et al54
reported a small, but statistically significant greater improvement
in VAS back pain score favoring KP (MD, 20.69; 95%
CI: 21.34 to 20.04).54 Only a single meta-analysis has directly
compared back pain scores in VP vs KP patients, in which no
significant difference in outcomes pain scores was identified.52
Two meta-analyses examined pooled comparisons of VP and KP
vs a combination of sham surgery and nonoperative treatment. In
2013, a pooled analysis performed by Anderson et al55 revealed
a mean difference in back pain VAS score of 0.73 (95% CI: 0.35-
1.10) for early and 0.58 (95% CI: 0.19-0.97) for late time points,
both of which favored surgical intervention over nonoperative
management (P , .001). More recently, Guo et al54 also identified
significantly greater improvement in VAS back pain score in
patients undergoing surgical intervention compared with sham or
nonoperative treatment (MD, 21.24; 95% CI: 22.20 to 20.29).
Disability and HRQOL
Significant variability exists in the measures used to report
disability and HRQOL outcomes in RCTs of surgical vs non-
operative treatment of VCFs as well as the time points at which
these measures were performed.50 In a more inclusive meta-
analysis comparing VP and KP with sham and nonoperative
treatment, functional outcome measured by the RMDQ and
ODI demonstrated significantly greater improvements in the VP
and KP group at both early and late time points (MD, 1.08; 95%
CI: 0.33-1.82 and MD, 1.16; 95% CI: 0.14-1.18, respectively),
although publication bias was identified in the studies. After
exclusion of a single outlying study,35 the mean differences
decreased, but the results remained statistically significant. Guo
et al54 also observed significantly better disability outcomes as
measured by the RMDQ in surgically treated patients at less than
3 months (MD, 24.97; 95% CI: 28.71 to 21.23]). However,
at 12-month or longer follow-up, HRQOL, as measured by the
SF-36, failed to demonstrate a difference between the treatment
arms (MD, 1.20; 95% CI: 21.33 to 3.72).
More focused comparisons of VP with either nonoperative
treatment or sham surgery failed to demonstrate improvements in
disability or HRQOL as measured on the RMDQ, QUALEFFO,
or EQ-5D at any time point.52 Comparisons between KP and
nonoperative treatment using a meta-analysis of patient-reported
outcome measure scores has not been performed.
NEUROSURGERY
Copyright Congress of Neurological Surgeons. Unauthorized reproduction of this article is prohibited
OSTEOPOROTIC VERTEBRAL COMPRESSION FRACTURES
Adverse Events
The most thorough examination of adverse events (AEs) related
to the surgical treatment of VCFs using percutaneous techniques
was a health technology assessment by Stevenson et al50 published
in 2014. Their systematic review and meta-analysis included both
RCTs as well as large observational studies enrolling $200
subjects and case reports of rare events. In defense of this
methodology, the authors argued that RCTs are underpowered to
detect AEs, and included populations may not be representative
of the target population.
Seven studies examining rates of image-identified cement
leakage were identified. Rates of cement leakage were found to
be 27% in 2 studies using KP and to range from 0% to 72% in 5
studies in which VP was performed. In total, cement leakage
occurred in 458 subjects. Only 2 cases of intracanal cement
extravasation were reported (0.004%), with only 1 requiring
reoperation for a radiculopathy. Asymptomatic pulmonary em-
bolism of cement was identified in 16 subjects (0.035%), 14 of
whom were identified in a cohort of 54 patients, all of whom
underwent routine postoperative computed tomography scans of
the chest.
Incident radiographic vertebral fractures were studied in 3
studies. At 12 months post-intervention, new fractures occurred
in 13.1% to 25% of control patients (n = 241), 16.5% to 26.6%
of patients undergoing VP (n = 155), and 33% of patients
undergoing KP (n = 115). At 2-year follow-up, these rates had
increased to 44.1% in 102 control patients and 47.5% in 118
subjects undergoing KP. Although new fractures are one of the
most common AEs after operative and nonoperative treatment
of VCFs, meta-analysis in multiple systematic reviews has
identified no significant difference in incident fracture rates
after surgical (VP or KP) vs nonoperative treatment of
VCFs.34,49,54,55 A single comparison of new fracture rates in
2 studies comparing VP with sham surgery or conservative care
also demonstrated no difference in incident fracture rates
(relative risk, 0.54; 95% CI: 0.09-3.38; P = .51).
In their meta-analysis of AE rates from 7 trials enrolling 855
patients, Guo et al54 identified no significant difference between
surgical treatment (VP/KP) vs sham and nonoperative treatment
(relative risk, 1.10; 95% CI: 0.85-1.43; P = .46). Similarly,
Buchbinder et al52 found no significant difference in serious AE
rates between VP and sham surgery (relative risk, 1.01; 95% CI:
0.21-4.85). Finally, a meta-analysis of 12-month mortality rates
from 3 studies demonstrated a trend toward improved mortality
outcomes in patients undergoing VP compared with nonoper-
ative treatment (MD, 0.68; 95% CI: 0.30-1.57).49,55
ECONOMIC EFFECTIVENESS OF VERTEBRAL
AUGMENTATION FOR VCFs
As the number of patients who are potential candidates for
vertebral augmentation for painful VCFs increases, rates of
osteoporosis increase, and the population ages, an understanding
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GOLDSTEIN ET AL
TABLE 3. Summary of Cost Analysis Studies of Vertebral Augmentation vs Nonoperative Treatment for Vertebral Compression Fracturesa
Base Case Patient Treatment QOL Data
Study Country Group Comparisons Study Characteristics Source QOL Instrument Cost Data
60
Edidin et al, USA N/A KP or VP vs Cost/LYG Weibull survival model N/A N/A KP
2010 Inclusion criteria: Medicare nonop Lifetime time horizon Medicare Females: $1863-
enrollees $65 y of age with an perspective 2010 costing 3%/y $3751/LYG
index VCF discounting Males: $2318-
$6687/LYG
VP
Females: $2452-
$6603/LYG
Males: $6621-
$13 543/LYG
Klazen et al,36 Netherlands Men and women 75 years of VP vs nonop Cost/QALY Within trial 1-y time VERTOS II EQ-5D (Dutch 22 685/QALY
2010 age with prevalent VCF horizon Health care perspective tariff)
and back pain ,6 wk) 2008 costing No discounting
Strom et al,58 UK Men and women 70 years of KP vs nonop Cost/QALY Markov cohort model FREE trial EQ-5D (UK tariff) 10 900/QALY
2010 age with T-score #22.5 Lifetime time horizon Health
and $1 VCF care perspective 2008 costing
3.5%/y discounting
Fritzell et al,57 Sweden Similar to Swedish patients KP vs nonop Cost/QALY Within trial 2-y time FREE trial EQ-5D (UK tariff) 101 626/QALY
2011 in FREE trial (mean age 72 horizon Societal perspective
y in KP and 75 y in control 2008 costing No discounting
arms, respectively)
Svedbom UK Females 70 years of age KP vs VP nonop Cost/QALY Markov cohort model FREE Trial, EQ-5D (UK tariff) KP vs nonop
et al,59 2012 with a prevalent VCF and Lifetime time horizon Health VERTOS II 3337/QALY KP
T-score #23.0 care perspective 2009 costing vs VP
3.5%/y discounting 19 706/QALY
Flug et al,61 USA N/A Inclusion criteria: VA (KP or VP) vs Cost (total for admission and N/A N/A Total cost
2013 patients admitted with nonop cost/d) Health care perspective VA: $26 074
a VCF Nonop: $15 507
Cost/d
VA: $2040
Nonop: $2069
Stevenson UK Women 70 years of age KP or VP or OPLA Cost/QALY Markov cohort model Multiple Multiple KP vs nonop
et al,50 2014 with a T-score of #23.0 vs nonop Lifetime time horizon Health 10 433/QALY
www.neurosurgery-online.com

care perspective 2010-2011 VP vs nonop

costing 3.5%/y discounting 7448/QALY
OPLA vs nonop
3788/QALY

a
KP, kyphoplasty; LYG, life-year gained; OPLA, operative placebo with local anesthesia; QALY, quality-adjusted life year; VA, vertebral augmentation; QOL, quality of life; VCF, vertebral compression fracture;
VP, vertebroplasty.

Copyright Congress of Neurological Surgeons. Unauthorized reproduction of this article is prohibited


of only the clinical effectiveness of operative and nonoperative
treatment options is no longer sufficient for todays spine care
provider. All treatment strategies are associated with significant
health care costs, so it is also necessary for physicians to be
familiar with the evidence regarding the cost-effectiveness of VP
and KP as applied to VCF management.
Recognizing this, Borgstrm et al56 performed a systematic review
of Embase, PubMed, EconLit, and National Health Service
Economic Evaluation Database to identify peer-reviewed published
investigations on the cost-effectiveness of vertebral augmentation in
patients with osteoporosis. Table 3 outlines the results of the 5 studies
identified by this review. Vertebral augmentation was found to be
cost-effective compared with nonsurgical management in the base
case results of 3 of the 5 studies, with incremental cost-effectiveness
ratios ranging from 3337 to 92 154 in 4 of the 5 studies.36,57-59
The authors reported that variations in cost-effectiveness were most
significantly influenced by the time horizon of the study, the effect of
treatment on quality of life, the time to realization of the treatment
effect, and reductions in length of stay, and mortality after vertebral
augmentation.
In addition to the European studies identified by Borgstrm
et al,56 2 North American cost analyses have also been
performed (Table 3). Using Medicare claims data from January
2005 to December 2008 and including relevant payments for
each patient up to 3 years after their VCF diagnosis, Edidin
et al60 observed that the difference in cumulative median costs
for VP and KP compared with nonoperative treatment ranged
from $8300 to $28 820 for VP and $12 580 to $18 500 for KP
depending on the age and sex of the groups examined.
Comparing KP with nonsurgical treatment, the cost per life-
year gained ranged from $1863 to $6687, whereas it was $2452
to $13 543 for VP compared with nonoperative treatment.
Finally, when KP was compared with VP, the cost per life-year
gained was 2$284 (cost saving) to $2399 for female patients
and 2$4878 (cost saving) to $2763 for males. Based on these
results, the authors concluded that surgical management of
VCFs is cost-effective in the Medicare population compared
with nonoperative treatment, and for patients in whom surgical
treatment is indicated, KP may even be cost-saving compared
with VP.
Subsequently, in 2013, Flug et al61 retrospectively reported
mean treatment costs of vertebral augmentation (n = 61 levels in
39 patients; KP = 40, VP = 21) vs nonoperative management (n =
209) in patients emergently admitted with vertebral compression
deformities. The mean total costs in the augmentation group
were $26 074 vs $15 507 in the nonsurgical cohort (P , .01).
The differences in cost appeared to be driven by differences in
length of stay (13.8 days in the augmented group vs 8.1 in the
medically managed group) that was significantly longer in both
groups than for patients typically treated on an elective basis. This
may have been due to more severe pain and higher levels of
dysfunction necessitating the subjects emergent admission to
hospital. Unfortunately, no investigation of HRQOL was
performed, and thus the cost-effectiveness of the different
NEUROSURGERY
Copyright Congress of Neurological Surgeons. Unauthorized reproduction of this article is prohibited
OSTEOPOROTIC VERTEBRAL COMPRESSION FRACTURES
treatments cannot be estimated or compared with the European
literature or the results of Edinin et al60
CONCLUSION
Osteoporotic VCFs are a common cause of pain, dysfunction,
and loss of mobility and independence in the elderly population.
Although many patients with symptomatic VCFs will respond
favorably to nonoperative management in the form of activity
modification, analgesics, and brace therapy, a high proportion will
fail to have adequate pain relief with this nonsurgical regimen.
Changes in rates of vertebral augmentation for treatment of
symptomatic VCFs and treatment recommendations demon-
strates that the therapeutic pendulum has swung from initial
enthusiasm for VP and KP, to reservations regarding the
effectiveness of these interventions, to an objective, evidence-
based approach to VCF management.
Meta-analysis of contemporary RCTs has demonstrated small,
but consistent greater improvements in back pain in patients
treated with either VP or KP compared with nonoperative
treatment at mid-term follow-up, although no difference has been
identified between VP and sham surgery. Current data would also
suggest that these improvements in back pain are accompanied by
significant, although clinically questionable, improvements in self-
reported disability. Further, no significant difference exists
between VP and KP with regard to complication rates, including
asymptomatic cement extravasation, and rates of incident VCFs
after treatment for a symptomatic fracture do not differ between
patients treated with VP, KP, or nonoperative means.
Given the high rates of morbidity and mortality associated with
nonoperative management and in light of the results from
contemporary cost-effectiveness investigations as well as multiple
systematic reviews and meta-analyses, it is possible that the
primary benefit associated with surgical treatment of VCFs may
be realized in the short term with shorter hospital stays, decreased
rates of complications, more rapid return of functional indepen-
dence, decreased rates of readmission, and fewer admissions to
skilled nursing or long-term care facilities. However, further trials
involving rigorous collection of clinical outcome, complication,
and both direct and indirect cost data are necessary to make this
determination.
Disclosure
The authors have no personal, financial, or institutional interest in any of the
drugs, materials, or devices described in this article.
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