Adverse Events; Complications - Bioventus Exogen Guia Del Usuario

b. Review information on fracture healing
Apart from Handolin et al. 19-20 the studies reported
above used ultrasound intensity levels ranging and bone formation
from 0.5 W/cm to 2 W/cm and no untoward
2 2
Two review articles
effects were noted. These intensities are 16 to 60
and basic science evidence for the EXOGEN
times higher than the intensity used in the
Ultrasound Bone Healing System. Their analyses
EXOGEN Ultrasound Bone Healing System. It is
suggested the EXOGEN Ultrasound Bone
reasonable to conclude that metal present in a
Healing System induced cellular reactions at
healing fracture would not affect the safety or
each phase of fracture healing from inflammation
effectiveness of the EXOGEN Ultrasound
through to endochondral ossification
Bone Healing System.
a number of preclinical studies have shown
acceleration of bone healing with the EXOGEN
e. Clinical
Ultrasound signal and increased mechanical
properties at the fracture site. Pilla et al.
No device-related adverse reactions or medical
two rabbit bilateral fibular osteotomy place-
complications related to the use of EXOGEN
bo-controlled studies, reported statistically
have been reported during the clinical
significant acceleration of ultrasound treated
studies .
2-11, 19, 21-37
fibulae versus the placebo side 1.7 and 1.4 times
faster, respectively. Wang et al.
Mode of Action
reported on ultrasound fracture treatment in a
model of bilateral closed femoral shaft fractures
a. Mode of Action
made in rats and stabilized by a Kirschner wire,
serving as an intramedullary rod. Ultrasound
The low-intensity pulsed ultrasound delivered by
treated fractures were shown to be significantly
the EXOGEN Ultrasound Bone Healing System is
stronger and stiffer than the controls, showing
a mechanical stimulus. This has been clearly
that the stimulatory effect of ultrasound on
demonstrated by experimental work on cadavers
fracture repair was not inhibited by the presence
in which tissue around an osteotomized bone
of a metallic internal fixation device.
moved in response to the ultrasound signal at a
frequency of 1kHz, the same frequency as the
Azuma et al.
pulse of the EXOGEN ultrasound signal. Tissue
micro-computed tomography, were able to
motion has been calculated to be of the order of determine that accelerated fracture healing in
0.5nm, approximately 1000 times less than
the ultrasound-treated group was typical of
"micromotion." As well as soft tissue movement,
normal bone healing. EXOGEN Ultrasound
it was demonstrated that the bone moved albeit
accelerated early, mid and late stages of fracture
on a smaller scale 38 . This work shows stimulation healing with maximum impact achieved when
with the EXOGEN Ultrasound Bone Healing applied throughout the healing process. Takikawa
System provides motion on a nanometer scale,
et al. 45 studied the impact of the EXOGEN
suggesting the mode of action is independent
Ultrasound Bone Healing System in a hypertro-
of fixation methods such as casting or external
phic non-union model demon-strating 50%
fixation. Mechanical energy is transformed into resolution in the active group versus 0% in the
biochemical energy by transduction at the cell
control group at 6 weeks.
membrane. One family of cell membrane
receptors that are responsible for this transduc-
c. Modes
tion are integrins. It has been demonstrated that
Effects on chondrocytes—Chondrocytes have
the EXOGEN ultrasound signal stimulates cells
been shown to respond to the EXOGEN signal
through an integrin pathway . Within this integrin
39
pathway, cytoskeletal organization, transcription by an increase in proteoglycan synthesis
factor activation, gene upregulation, protein (mediated by calcium signaling) and the
increase in aggrecan mRNA
synthesis and increased cell proliferation have
all been observed.
23
Response of marrow cells to the EXOGEN
ultrasound signal—The EXOGEN signal
accelerated the differentiation of mesenchymal
25,40 have assessed the clinical
cells when cultured in a system designed to
promote chondrocytic differentiation
Periosteal cell response—Human periosteal cell
cultures responded to low intensity pulsed
ultrasound by increasing expression of alkaline
. In addition, phosphatase, osteocalcin and VEGF. In addition
33
long term treatment (4 weeks of 20-minute daily
treatment) increased the level of mineralization
in these cultures 48 .
in
34,41
Osteoblast differentiation—MMP13 and alkaline
phosphatase are two enzymes key to the process
of mineralization. Unsworth et al.
an increase in both these enzymes in MC3T3-E1
cultures after stimulation with EXOGEN ultra-
and Yang et al.
42 43
sound. Further evidence that ultrasound affects
the mineralization process comes from Saito et
al. 50 who demonstrated accelerated calcium
accumulation in MC3T3-E1 cultures. Significant
increases (8.6-fold and 3.6-fold higher than
untreated controls) were seen at day 25 and day
35 respectively. Collectively the findings of these
studies demonstrate that in a pre-osteoblastic
culture system EXOGEN low intensity pulsed
ultrasound accelerates differentiation along the
, through histological analysis and osteoblastic lineage. Animal studies have shown
44
that such effects in a fracture environment can
benefit the formation of a mineralized callus,
stabilizing the fracture and increasing the strength
of the bone.
Clear evidence exists that the EXOGEN
Ultrasound Bone Healing System accelerates the
healing process at all stages of fracture repair
In-vitro evidence supports this by demonstrating
effects on various
cell types, stimulating proteins involved
in various biological processes and demonstrat-
ing acceleration of some processes
in organ culture.
.
43,46

Adverse Events

Unlike conventional (physical therapy)
ultrasound devices, EXOGEN is incapable of
47 .
producing harmful temperature increases in body
tissue . The ultrasound output
14
intensity of EXOGEN is 30 mW/cm
is typically only 1% to 5% of the output
intensity of conventional therapeutic
ultrasound devices. The ultrasound
intensity is comparable to diagnostic ultrasound
(1 to 50 mW/cm ), such as the intensities used in
2
obstetrical sonogram procedures (fetal monitor-
ing). In addition, there is no evidence of non-ther-
mal adverse effects (cavitation).
49 demonstrated

Complications

No device-related adverse reactions or medical
complications related to the use of EXOGEN
were reported during the clinical studies. Some
patients have experienced mild skin irritation
caused by skin sensitivity to the gel. If you feel
your skin is sensitive to the gel, you may change
the gel to mineral oil or glycerin. In the distal
radius study, one patient complained of pain
during treatment but they no longer had the pain
by the next follow up visit; and one patient,
complaining of pain, withdrew from the study.
.
44,51
and
2
24