Treatment of osteoporotic
vertebral compression fractures
Caroline A.H. Klazen
Thesis, University Utrecht
© C.A.H. Klazen, 2010
The copyright of the articles that have been published or accepted for publication
has been transferred to the respective Journals.
Printed by Gildeprint drukkerijen, Enschede, The Netherlands
Dr. M. Sluzewski
Karin van Rijnbach
Publication of this thesis was financially supported by:
Raad van Bestuur Medisch Spectrum Twente
Maatschap Radiologie Medisch Spectrum Twente
Treatment of osteoporotic
vertebral compression fractures
Behandeling van osteoporotische wervelfracturen
(met een samenvatting in het Nederlands)
ter verkrijging van de graad van doctor
aan de Universiteit Utrecht
op gezag van de rector magnificus, prof. dr. J.C. Stoof
ingevolge het besluit van het college voor promoties
in het openbaar te verdedigen
op vrijdag 12 november 2010 des middags te 2.30 uur
Caroline A. H. Klazen
geboren op 7 april 1977 te Berkel-Enschot
Prof. dr. W.P.Th.M. Mali
Prof. dr. J. de Vries
Dr. P.N.M. Lohle
Dr. H.J.J. Verhaar
The research described in this thesis was supported by a grant from the Netherlands
Organisation of Health Research and Development (ZonMW) and COOK Medical
General introduction 7
Clinical course of pain in acute, osteoporotic, vertebral
JVIR 2010; 21:1405-09
Chapter 3 VERTOS II: Percutaneous vertebroplasty versus conservative
therapy in patients with painful osteoporotic vertebral
compression fractures; rationale, objectives and design of
a multicenter randomized controlled trial.
Trials 2007; 8: 33.
Vertebroplasty versus conservative treatment in acute,
osteoporotic vertebral compression fractures (Vertos II):
an open-label randomised trial.
Lancet 2010; 376: 1085-1092
Percutaneous Vertebroplasty Is Not a Risk Factor for New
Osteoporotic Compression Fractures: Results from VERTOS II.
AJNR Am J Neuroradiol 2010; 31:1447–50
Percutaneous Vertebroplasty and Pulmonary Cement
Embolism: Results from VERTOS II
AJNR Am J Neuroradiol 2010; 31:1451–53
Postprocedural CT for perivertebral cement leakage in
percutaneous vertebroplasty is not necessary—results
from VERTOS II
Neuroradiology 2010 May 5 (Epub ahead of print)
Percutaneous Vertebroplasty and Procedural Pain
AJNR Am J Neuroradiol 2010; 31:830-1
General Discussion 107
Chapter 10 Summary
Samenvatting in het Nederlands
Osteoporotic Vertebral Compression Fractures
Vertebral compression fractures (VCFs) following osteoporosis are common in the
elderly population with an estimated 1.4 million clinically new VCFs worldwide
annually 1. About one third of new VCFs come to medical attention, suggesting
that most VCFs are either asymptomatic or with tolerable symptoms 2. Patients
with an acute VCF can present with severe back pain that can last for weeks to
months. The percentage of patients with chronic pain due to an osteoporotic
VCF assumed in literature is 10%-20%3, 4. However, valid evidence is lacking. In
Chapter 2 we prospectively determined the natural course of pain in patients
with conservatively treated acute osteoporotic vertebral compression fractures.
Indications and timing of percutaneous vertebroplasty (PV) may depend on the
natural course of an osteoporotic VCF
Treatment of Osteoporotic Vertebral Compression Fractures
Differential diagnosis of pain from an osteoporotic VCF includes myalgia,
degenerative disease and a herniated disc. Anamnesis, physical examination
and Magnetic Resonance Imaging (MRI) of the spine are needed to differentiate
between these causes. Pain due to an osteoporotic VCF is mostly a focal, sharp
pain at the level of the VCF and at adjacent regions, typical during movement
and on physical exercise. A herniated disc typically presents with radiculair pain.
A VCF can be simply diagnosed on a plain spine radiograph. However, MRI is
needed to discriminate between old, healed VCFs and subacute, non-healed VCFs.
In non-healed VCFs bone edema is present in the vertebral body 5. When MRI is
contraindicated, a bone scintigram should be performed to demonstrate activity
in the vertebral body and the number of vertebral bodies that are involved6.
Without a recent MRI or bone scintigram, it is impossible to demonstrate that the
vertebral compression fracture is the cause of pain.
Treatment of osteoporotic VCFs is treatment of pain. Until recently, bed rest,
analgesia, cast and physical support were the only treatment options for painful
VCFs. Bed rest may result in loss of bone density and muscle mass, while braces
are often poorly tolerated. In general, osteoporotic VCFs heal within 6-8 weeks.
However, some patients develop invalidating chronic pain despite conservative
treatment. For these patients, PV was introduced as an adjunct treatment of pain.
The injected bone cement agglutinates the microfractures in the vertebral body
and as such provides immediate and sustained pain relief.
To prevent new fractures in patients with osteoporosis, adjuvant biphosphonate
medication is important. The risk of a second osteoporotic VCF within the first
year after a VCF is about 20% 7. This risk increases with the number and severity of
pre-existing osteoporotic VCFs. Bisphosphonates reduce this proportion almost
by half 8
In 1984 PV was developed in France for the treatment of painful aggressive
vertebral angioma 9. In the following years the indication for PV was expanded to
vertebral fractures caused by osteoporosis, trauma, malignant or benign vertebral
tumors and vertebral osteonecrosis. Presently, PV is most frequently performed to
treat patients with painful osteoporotic VCFs.
Figure 1. MRI with bone edema of Th10 and Th9.
PV is performed in an angiography suite on a single or biplane angiographic
system (Figure 1). Local anaesthesia is infiltrated from the skin to the periosteum of
the targeted pedicle. Some patients receive additional intravenous fentanyl during
the procedure. Pain management during PV is discussed in Chapter 8. Two 11 or
13 Gauge bone biopsy needles are placed transpedicular in the fractured vertebral
body. Polymethylmetacrylate bone cement is injected through the bone biopsy
needles under continuous fluoroscopic monitoring to timely identify local cement
leakage and cement migration into the venous system towards the lungs. Patients
can be mobilized several hours after the procedure. Post procedural care consists
of physiotherapy, osteoporosis medication and additional pain medication if
Clinical results of Percutaneous Vertebroplasty
Since its introduction, this minimally invasive technique has received widespread
recognition with effective pain reduction both on short- and long-term 10-19.
A recent systematic literature review suggest effectiveness of PV in terms of pain
relief 19. However, the included prospective and retrospective follow-up studies do
not comprise control groups to compare with. The VERTOS I study randomized a
small group of patients with a subacute VCF and found immediate pain relief and
improved mobility on short-term follow-up 20. The study was terminated early due
to many crossovers.
Recently, two randomized studies using a sham control intervention reported
on clinical outcome one 21 and six 22 months after PV in patients with osteoporotic
VCF up to one year old. Both studies seem to indicate that PV and sham treatment
are equally effective. However, clinical interpretation of these studies is hampered
by including also patients with subacute and chronic fractures instead of only acute
fractures, lack of a control group without intervention, not using bone edema on
MRI as a consistent inclusion criterion, lack of specific physical examination and
some other methodological problems 23, 24.
We designed an open-label randomized controlled trial (VERTOS II) to clarify
whether PV has additional value compared with optimal pain treatment in a well
defined group of patients with acute VCFs. Study rationale, objectives and design
are described in Chapter 3. In Chapter 4 the main outcomes of the VERTOS II study
are analysed: pain relief, cost-effectiveness, quality of life and function.
Figure 2. PV Procedure
a. vertebral fracture L1. b.needle placement under fluoroscopic guidance. c. two transpedicular needle are placed. d. mixing
cement and filling 1cc syringes. e. syringes with cement are placed on the needle. f. cement injection. g. cement in the
vertebral body. h and i. CT of the treated vertebral body.
Adverse effects of Percutaneous Vertebroplasty
Controversy exists as to whether PV increases the risk for new VCFs during follow-
up. In Chapter 5 we assessed the incidence of new VCFs in patients with acute
VCFs randomized to PV and conservative therapy. In addition, we assessed further
height loss of the treated vertebral bodies with both therapies.
Cement leakage after PV outside the vertebral body is frequently detected.
Most leakages are into adjacent disks or segmental veins and most patients are
asymptomatic. However, radiculopathy, myelopathy and pulmonary cement
embolism (Figure 3) is occasionally reported 19. In Chapter 6 we assessed the true
incidence of pulmonary cement embolism during follow-up in a large proportion
of patients from the VERTOS II trial. We used baseline and follow-up CT to assess the
incidence, anatomical location, and clinical impact of perivertebral cement leakage
on short- and long-term in a large patient cohort; these results are described in
In the general discussion, Chapter 9, the overall findings are placed in a larger
perspective. A summary of the results of this thesis is presented in Chapter 10.
Figure 3. Pulmonary cement embolus in the left pulmonary artery.
Figure 4. Cement leakage in a segmental vein
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