Viscosity of PMMA Bone Cement in Percutaneous Vertebroplasty for Osteoporotic Vertebral Compression Fractures: A Randomized Controlled Trial

With over 15000 to 20000 new symptomatic cases each year in the Netherlands,
Osteoporotic Vertebral Compression Fractures (OVCFs)comprehend a substantial
social problem with corresponding burden on the health care system.
Percutaneous augmentation, with Percutaneous VertebroPlasty (PVP) as its main
proponent and by far the most executed procedure, is currently the only
available interventional treatment modality for this problem. After PVP , 80 -
90% of patients experience an immediate, substantial and durable pain relief
which enables them to return to a more active lifestyle and prevents them from
complications due to a bed-bound lifestyle, as well as reducing the continuing
burden on health care systems.

PVP as a treatment modality for OVCFs shows a rather high incidence of cement
leakage, especially when assessed using postoperative CT-scanning (gold
standard). Cement leakage, however, was considered mostly asymptomatic and
harmless to the patient.
Recently, however, several studies have been published indicating clincally
revelevant sequelae of cement leakage may be more common than previously
thought. The first, and thus far only high quality, prospective study on the
occurrence of Pulmonary Cement Emboli (PCE) after PVP in OVCFs reported an
unexpectedly high incidence: in 18 of 78 (23%) patients one or more PCE were
detected. More high-quality studies are required to confirm or discard this
finding. Also, several studies found an association between cement leakage to
the intervertebral space and induction of new, adjacent OVCFs - the very
problem the procedure is treating!

Based on the available literature, the current perception is that increasing
viscosity of PMMA bone cement in PVP for OVCFs reduces the incidence of cement
leakage, but concomittantly might limit the penetration and interdigitation of
bone cement into the cancellous bone, leading to a more clump-like filling
pattern with the potential to meaningfully alter the biomechanics of the
vertebral column and induce new OVCFs. Only the former fact, i.e. reduction of
cement leakage, has been shown by us and several international studies. The
other claims could are not confirmed and also could not be established by our
own study (accepted to Spine) and therefore appear unlikely.

Considering the substantial incidence of cement leakage, the increasing
evidence indicating a higher frequency of clinically revelant sequelae of
cement leakage than previously assumed and the gain expected to be obtained
from usage of high viscosity bone cements, a compelling need for the definitive
establishment of the effects of bone cement viscosity exists. Currently, this
is absent and the very reason this study is proposed.

Establishment whether usage of high viscosity PMMA bone cement in PVP for OVCFs
leads to a reduction in leakage incidence compared to usage of conventional
(low-medium) viscosity PMMA bone cement in PVP for OVCFs.

Since evidence is scarce or conflicting, incidence of cement leakage related
sequelae will assessed, reported and subsequently related to viscosity of bone
cement used. Specifically mentioned regarding this matter are Pulmonary Cement
Emboli (PCE) after PVP and new OVCFs (whether in the presence of cement leakage
etc).

In addition, sensitivity and specificity of radiography of the thorax compared
to CT-scanning of the thorax (gold standard) in detection of PCE are unknown
and will be determined, assessing feasability of chest radiography for routine
screening of PCE .

This study is designed as a randomized, controlled trial comprising two arms:
one group will receive PVP for OVCFs using low-medium viscosity PMMA bone
cement (the control group) and the other group will receive PVP for OVCFs using
high viscosity PMMA bone cement (the treatment group). Analysis will be
performed on both an intention-to-treat basis and on per-protocol basis.

o Primary outcome: Incidence of cement leakage per treated vertebra.

o Secondary outcomes:
* Incidence and clinical relevance of pulmonary and cardiac
cement emboli. The association between emboli and (type of)detected
(local) cement leakage will be assessed.
* Incidence of new (adjacent) OVCFs during the first year after
PVP. The association between new OVCFs and (type of) detected
cement leakage will be assessed.
* Sensitivity and specificity of conventional radiography of
the thoracic region in detection of cement leakage compared to CT-
scanning of this region (gold standard).

After the inclusion of forty patients, an interim analysis will be performed.
When a statistically significant and clinically relevant difference regarding
the aforementioned major adverse outcomes in one arm is detected, it may be
considered unethical to continue the study and termination of the study will be
considered.

PVP with usage of either conventional (low-medium) viscosity PMMA bone cement
or high viscosity PMMA bone cement.

The PVP-procedure is performed on a biplane angiography unit using conscious
sedation. A 10G vertebroplasty needle is gently hammered into the (anterior
third of the) VB and a bone biopsy will be obtained, followed by injection of
PMMA bone cement until a satisfactionary distribution of the cement, i.e.
symmetrical filling of the central and anterior parts of the VB, was obtained
or when cement leakage was noted. When necessary, a second needle was advanced
into the VB through the contralateral pedicle, followed by injection of cement.

Patients are encouraged to start mobilizing after 2 hours and will leave the
hospital at the end of the day. The procedure itself takes less than 30
minutes.

The only additional burden for patients participating in the trial (compared to
patients who do not participate) is additional radiography and CT-scanning of
the chest. Practically, this translates to:
- A slightly longer postoperative work-up, although CT-scanning of the chest
will be performed in the same session as the routine postoperative Ct-scanning
of the treated levels.
- A somewhat higher radiation exposure, although not excessively since it
concerns routine imaging procedures.
- Possible psychological and physical consequences due to accidental findings
of (possibly) pathological nature. Policy of LUMC is to always inform the
patient regarding such findings, possibly leading to distress or difficult
(treatment) desicions. On the other hand, however, early detection might be
beneficial due to generally better chances of curative treatment, which
otherwise might not have been detected (yet).