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Effects of suppression of estrogen action by the p450 aromatase inhibitor letrozole on bone mineral density and bone turnover in pubertal boys.
[aromatase deficiency]
The
essential
role
of
estrogen
(
E
)
in
regulation
of
developing
peak
bone
mass
in
males
was
confirmed
when
young
adult
men
were
described
who
can
not
respond
to
or
produce
E
because
of
defective
E
receptor
alpha
or
P-
450
aromatase
enzyme
,
respectively
.
These
men
had
significantly
reduced
bone
mineral
density
(
BMD
)
despite
normal
or
supranormal
androgen
concentrations
,
and
E
administration
improved
BMD
in
the
men
with
aromatase
deficiency
,
whereas
testosterone
(
T
)
was
ineffective
.
Because
new
P
450
aromatase
inhibitors
may
prove
to
be
potential
drugs
in
various
growth
disorders
,
the
effect
of
suppression
of
E
action
on
developing
peak
bone
mass
has
to
be
closely
evaluated
.
In
this
study
,
we
explored
the
effects
of
suppression
of
E
synthesis
on
bone
metabolism
in
pubertal
boys
.
A
total
of
23
boys
with
constitutional
delay
of
puberty
were
randomized
to
receive
T
and
placebo
or
T
and
a
specific
and
potent
P
450
aromatase
inhibitor
,
letrozole
.
We
determined
BMD
in
the
lumbar
spine
and
the
femoral
neck
.
Bone
resorption
was
studied
by
measuring
the
serum
concentration
of
cross-linked
carboxyterminal
telopeptide
of
type
I
collagen
by
two
different
methods
(
CTx
and
ICTP
)
,
and
bone
formation
by
determining
the
serum
concentrations
of
carboxyterminal
propeptide
of
type
I
procollagen
(
PICP
)
,
osteocalcin
,
and
alkaline
phosphatase
.
We
demonstrated
previously
that
,
during
treatment
with
T
and
placebo
,
the
concentrations
of
androgens
and
E
increased
.
During
treatment
with
T
and
letrozole
,
the
E
concentrations
remained
at
the
pretreatment
level
,
but
the
androgen
concentrations
increased
;
the
increase
in
the
T
concentration
was
more
than
5
-
fold
higher
than
during
treatment
with
T
and
placebo
.
We
did
not
observe
any
significant
differences
in
the
changes
in
bone
mineral
content
,
BMD
,
or
bone
mineral
apparent
density
,
an
estimate
of
true
volumetric
BMD
,
between
the
treated
groups
.
Lumbar
spine
bone
mineral
apparent
density
increased
in
both
treated
groups
;
but
in
the
T
-
plus
letrozole-treated
group
,
the
increase
was
statistically
significant
only
6
months
after
discontinuation
of
letrozole
treatment
.
All
bone
resorption
and
formation
markers
increased
during
treatment
with
T
and
placebo
.
During
treatment
with
T
plus
letrozole
,
CTx
,
PICP
,
and
osteocalcin
remained
unchanged
,
whereas
ICTP
and
alkaline
phosphatase
increased
.
Thus
,
1
-
yr
treatment
with
this
new
P
450
aromatase
inhibitor
in
pubertal
boys
is
unlikely
to
be
associated
with
any
major
harmful
effect
on
developing
peak
bone
mass
.
However
,
to
convincingly
exclude
such
effects
,
particularly
rare
or
minor
ones
,
will
require
a
study
with
a
larger
sample
size
;
and
thus
,
close
follow-up
of
bone
metabolism
during
treatment
with
P
450
aromatase
inhibitors
is
still
warranted
.
Diseases
Validation
Diseases presenting
"bone mass"
symptom
aromatase deficiency
dentin dysplasia
dentinogenesis imperfecta
familial hypocalciuric hypercalcemia
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