Bioventus EXOGEN Guia Del Usuario página 25

demonstrated significantly smaller loss of
reduction compared to the placebo group
(p<0.01).
Acceleration of Conservatively
Treated Fresh Tibial Fractures
Study Design
Placebo-controlled, randomized, double-blind
multi-centre study with the prospectively defined
primary end-point of a combination of clinical and
radiographic healing (3 out of 4 cortices bridged
as judged by the blinded principal investigator).
67 patients with conservatively treated closed
or grade-I open, cortical tibia fractures were
randomized into the EXOGEN treated and
control groups (Heckman et al. ).
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Patient population and demographics
The demographics of the trial participants were
comparable across treatment and control groups
with regard to age, sex, fracture characteristics,
interval between fracture and commencement of
fracture, duration of follow-up, and days to start
weight-bearing.
Evaluation schedule
Treatment was started within seven days of the
fracture, and continued for 20 weeks or until the
clinical investigator judged the fracture to have
healed. All patients were scheduled for follow-up
radiographs at 4, 6, 8, 10, 12, 14, 20, 33 and 52
weeks after the fracture. Clinical follow-up
evaluations were performed at the time of any
cast change (usually at 6 and 10 weeks) and at
the follow-up visit when radiographic evaluation
indicated the fracture had healed sufficiently to
allow removal of the cast.
Clinical Results
EXOGEN treatment induced a 38% acceleration
in achieving the prospectively defined primary
end-point of a combination of clinical and
radiographic healing (96±4.9 days in the active
group versus 154±13.7 days in the control group;
p<0.0001).
Analysis of fresh fracture studies:
Cook et al. pooled the data from the tibia and
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distal radius studies to analyze the impact of low
intensity pulsed ultrasound on the incidence of
delayed unions, and on the healing time of
smokers. Using a 150 day definition of delayed
union, Cook et al. determined that the EXOGEN
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Ultrasound Bone Healing System had a statisti-
cally significant effect (p<0.003) on the rate of
delayed unions (treated group 6% versus control
group 36%). Cook et al. also demonstrated a
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significant reduction in the healing time of
smokers for fractures of the tibia and distal
radius.
Other fresh fracture studies:
In addition to long bones, the effect of the
EXOGEN Ultrasound Bone Healing System on
fractures of other types of bone has also been
clinically studied. A single center, prospective,
randomized, double-blind, placebo-controlled
study of 40 scaphoid fractures , demonstrated
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a statistically significant 31% acceleration in the
primary end-point of clinical plus radiographic
healing (active 43 days; control 62 days; p<0.01)
and 41% improvement in percentage trabecular
bridging at 6 weeks (active 81%, control 55%,
p<0.05). A smaller (n=20) single-center, pro-
spective, randomized, double-blind, placebo
controlled study of Jones' fractures
all actively-treated fractures healed within 56
days whilst only 60% of placebo-treated fractures
had healed by 87 days, and 20% had still not
healed after 140 days. In addition, the active-
ly-treated group reached pain free status 31 to
70 days earlier than the placebo group, and on
average took only half the rehabilitation time.
Safety
a. Gross Pathology
Several studies were conducted to assess the
safety of EXOGEN as part of the FDA summary
of safety & effectiveness. Results from a placebo
controlled in-vivo study on rabbits with bilateral
midshaft fibular osteotomies showed no deleteri-
ous effects of EXOGEN as evidenced by
pathological, hematological, and histological a
nalysis .
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b. DNA Analysis
Analysis of the effects of EXOGEN on chromo-
some of bone marrow cells from a rabbit
mid-shaft radius osteotomy reported no
measurable, significant, detrimental effects
c. Temperature
EXOGEN's acoustic output is 20 to 100 times
less than that of other therapeutic ultrasound
devices currently available.
An independent university-based medical expert
in ultrasound
is incapable of producing temperature elevations
greater than 1°C. Such temperature elevations
are not considered significant and the potential
for detrimental thermal effects is not a concern.
d. Metals & Implants
Several reference articles have focused on
conventional therapeutic ultrasound's effect on
surgical metallic implants. Lehman et al.
reported that, based on histological studies,
ultrasound applied in the presence of metal
implants did not produce any untoward effects.
In addition, it has been shown that low intensity
ultrasound does not compromise the integrity of
a standard orthopaedic stainless steel fixation
plate . After 30 hours of continuous exposure,
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no changes or effects could be detected.
Temperature—Gersten
showed
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ture rises were smaller with metal than with bone
at the same depth, and that the presence of metal
was not a contraindication to the use of ultra-
sound.
Migration—Lotsova
carried out with Kirschner needles, used as
fixation in ultrasound-treated patients did not
affect migration of the pins or affect the structural
integrity of the pins as determined by metallo-
graphic analysis.
Degradation—Skoubo-Kristiansen and
Sommer concluded that as a result of ultrasound
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treatment no effect was observed on fixation
screws or the torques necessary for loosening
the screws in an in-vivo study. The compatibility
of the EXOGEN Ultrasound signal on bioabsorb-
able screws has also been investigated in-vitro
and clinically. Handolin et al.
with EXOGEN had no effect on the mechanical or
molecular properties of biodegradable self-rein-
forced poly L-lactide screws and thus biocompati-
bility between the screws and EXOGEN was
good, with no effect on the biodegradation rate.
.
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concluded EXOGEN
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reported that tempera-
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reported that investigations
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showed treatment
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