Calcium and Phosphorus Metabolism in Osteomalacia. V. The Effect of Varying Levels and Ratios of Calcium to Phosphorus Intake on their Serum Levels, Paths of Excretion and Balances, in the Presence of Continuous Vitamin D Therapy


Liu, S.H.; Su, C.C.; Chou, S.K.; Chu, H.I.; Wang, C.W.; Chang, K.P.

Journal of Clinical Investigation 16(4): 603-611

1937


In two patients, one with osteomalacia. being treated by vitamin D, and the other with syphilitic osteitis of radius and tibia, the serum Ca was fairly constant, but in the osteomalacia case the serum P tended to decrease with increased Ca: P ratio in the diet. A reciprocal relation between urinary Ca and P excretion, and intake was shown in both cases. Faecal Ca and P were also related to intake (see also Abst. 3007, Vol. 5). Retention of both Ca and P was more dependent on the Ca than on the P intake although both were required in fairly large amounts, and with an optimum Ca: P ratio of 2 in order to obtain good healing of the osteomalacia. Continuous administration of vitamin D in this study gave no better healing than the limited dosage in previous cases (see Abst. 2116, Vol. 4).

CALCIUM
AND
PHOSPHORUS
METABOLISM
IN
OSTEOMALACIA.
V.
THE
EFFECT
OF
VARYING
LEVELS
AND
RATIOS
OF
CAL—
CIUM
TO
PHOSPHORUS
INTAKE
ON
THEIR
SERUM
LEV—
ELS,
PATHS
OF
EXCRETION
AND
BALANCES,
IN
THE
PRESENCE
OF
CONTINUOUS
VITAMIN
D
THERAPY
BY
S.
H.
LIU,
C. C.
SU,
S.
K.
CHOU,
H.
I.
CHU,
C.
W.
WANG
AND
K.
P.
CHANG
(Department
of
Medicine,
Peiping
Union
Medical
College,
Peiping,
China)
(Received
for
publication
January
8,
1937)
Osteomalacia
is
a
bone
disease
more
commonly
seen
and
with
greater
clinical
implications
in
North
China
than
elsewhere
(1,
2,
3).
The
prin-
cipal
cause
of
the
skeletal
demineralization
re-
sides
in
vitamin
D
deficiency,
a
combination
of
its
lack
in
the
diet
and
exclusion
of
sunlight.
By
reason
of
such
deficiency,
calcium
given
by
mouth
fails
to
be
absorbed.
Poor
intestinal
absorption
rather
than
excessive
elimination
is
incriminated
because
it
has
been
demonstrated
by
the
studies
of
Hannon
et
al.
(4)
that
the
endogenous
calcium
metabolism
in
patients
with
osteomalacia
on
low
intake
is
within
normal
limits
and
that
calcium
administered
parenterally
is
largely
retained.
Un-
der
such
circumstances
while
the
endogenous
de-
structive
activity
in
the
bones
may
not
be
exces-
sive,
the
reparative
process
is
very
much
inter-
fered
with
through
defective
intestinal
absorption
so
that
skeletal
decalcification
inevitably
ensues.
The
limited
intake
of
calcium
in
common
Chinese
dietaries
(5),
and
periods
of
mineral
stress
inci-
dent
to
pregnancy
and
lactation
are
some
of
the
contributing
factors
that
enter
into
the
pathogene-
sis
of
osteomalacia.
Studies
of
the
effect
of
vitamin
D
in
the
treat-
ment
of
osteomalacia
(4,
6)
demonstrate
the
re-
markable
'conserving
action
of
vitamin
D
on
cal-
cium
and
phosphorus
metabolism.
As
a
result
of
its
administration,
intestinal
absorption
is
pro-
moted
and
endogenous
elimination
is
decreased
so
that
large
quantities
of
calcium
and
phosphorus
are
available
for
deposition
in
the
bones.
The
ac-
tual
amount
of
calcium
and
phosphorus
retained
depends
upon
the
level
and
ratio
of
intake
of
these
elements.
It
has
been
shown
in
two
patients
with
osteomalacia
undergoing
reparation
initiated
by
vitamin
D
(7)
that
calcium
retention
varied
di-
rectly
with
calcium
intake
while
phosphorus
re-
tention
was
limited
by
both
calcium
and
phos-
phorus
intake.
Fecal
calcium
likewise
varied
directly
with
calcium
intake
while
fecal
phos-
phorus
was
parallel
with
both
calcium
and
phos-
phorus
intake.
When
calcium
supply
is
limited
in
relation
to
phosphorus
(low
Ca
:
P
ratio)
prac-
tically
all
the
calcium
absorbed
is
deposited,
none
appearing
in
the
urine.
On
the
other
hand,
when
phosphorus
supply
is
short
compared
with
calcium
(high
Ca
:
P
ratio),
all
the
available
phosphorus
is
retained
and
urinary
phosphorus
vanishes.
Con-
servation
of
excretion
through
the
urinary
tract
and
efficient
absorption
through
the
intestinal
ca-
nal
account
for
the
markedly
positive
balances
in
osteomalacia
when
reparation
is
brought
about
under
the
influence
of
vitamin
D.
Similar
observations
on
the
effects
of
variations
of
the
levels
and
ratios
of
calcium
to
phosphorus
intake
on
their
serum
levels,
paths
of
excretion
and
balances
have
been
made
on
another
patient
with
healing
osteomalacia.
But
in
contrast
to
the
previous
patients
who
received
vitamin
D
only
prior
to
the
observations,
the
present
subject
was
given
vitamin
D
throughout
the
entire
study
so
as
to
obviate
any
uncertainty
in
ascribing
the
metabolic
results
obtained
to
vitamin
D
action.
Moreover,
attempt
was
made
in
the
present
study
to
secure
more
nearly
metabolic
equilibrium
by
using
three
4-day
periods
for
each
level
or
ratio
of
dietary
intake.
The
data
obtained
from
this
pa-
tient,
together
with
those
from
another
subject
having
syphilitic
osteitis
of
right
radius
and
tibia
without
general
metabolic
disturbance,
taken
as
a
control,
constitute
the
basis
of
discussion
in
the
present
communication.
PROCEDURE
The
clinical
histories
of
the
two
subjects
are
briefly
described
in
the
appendix.
Subject
1,
H.
F.
M.,
was
a
woman
of
32
with
advanced
osteo-
603
Articles
of
food
Millet
Rice
Glutinous
rice
Oatmeal
White
wheat
flour
Mung
bean
flour
Peanut
Egg
Egg
white
Pork
Chicken
Beef
Aroid
Potato
Sweet
potato
Carrot
Turnip
Cabbage
Onion
Chinese
lettuce
Spinach
Apple
Banana
Orange
Lard
Butter
Sesame
oil
Table
salt
Sugar
Soy
bean
sauce
Protein
Carbohydrate
Fat
Calories
Calcium
Phosphorus
Nitrogen
Diet
1
300
300
100
50
30
40
4
60
71
286
120
2508
0.178
0.402
10.82
D
Vitamin
Subject
1
(H.
F.
M.)
Subject
2
(L.
Y.
H.)
Diet
1
50
50
150
100
50
50
100
50
32
4
21
5
65
102
63
1235
0.138
0.914
10.40
Diet
2
50
150
75
50
50
50
50
100
50
45
4
20
5
59
192
70
1642
0.140
0.627
9.12
Diet
2
200
50
200
100
25
50
50
100
31
20
20
6
24
62
392
76
2500
0.118
0.582
8.69
Diet
3
100
100
150
100
100
100
50
100
50
50
6
80
307
76
2232
0.173
1.094
11.51
Diet
5a
Diet
5b
20
16
150
120
100
80
300
240
100
50
50
70
4
50
5
58
284
73
2022
0.176
0.324
8.28
80
40
40
56
3.2
40
4
46
227
58
1614
0.140
0.259
6.64
Diet
3
50
200
30
50
50
75
50
100
150
50
50
4
20
5
69
232
79
1923
0.191
0.925
10.68
Diet
4
50
100
75
25
30
25
75
75
50
50
100
50
4
24
5
77
211
94
2000
0.181
1.163
12.39
604
S.
H.
LIU,
C.
C.
SU,
S.
K.
CHOU,
H.
I.
CHU,
C.
W.
WANG
AND
K.
P.
CHANG
malacia
of
seven
years'
duration.
While
skele-
tal
rarefaction
and
deformities
'were
marked,
her
serum
calcium
and
phosphorus
were
within
nor-
mal
limits.
She
was
placed
on
various
diets,
the
compositions
of
which
are
given
in
Table
I.
All
the
diets
were
low
in
calcium
but
contained
vary-
ing
amounts
of
phosphorus.
The
desired
high
levels
of
calcium
intake
were
attained
by
giving
appropriate
quantities
of
a
saturated
solution
of
calcium
lactate
(7.7
per
cent).
At
a
given
level
of
calcium
intake,
the
phosphorus
level
was
pro-
gressively
increased
by
giving
Diets
5,
2,
3
and
4
in
that
order.
There
were
'altogether
3
levels
of
calcium
and
4
levels
of
phosphorus
intake,
making
a
total
of
12
different
ratios.
Three
four-day
pe-
riods
were
devoted
to
each
ratio
of
calcium
to
phosphorus
intake.
The
first
five
periods
con-
cerned
preliminary
observations
without
vitamin
D,
but
after
that
1
cc.
of
Vigantol,
an
oily
solution
of
irradiated
ergosterol
containing
15,000
interna-
tional
units
of
vitamin
D
per
cc.,
was
given
daily.
Subject
2,
L.
Y.
H.,
was
a
man
of
24
with
syphilitic
osteitis
of
right
radius
and
tibia,
the
rest
of
the
skeleton
showing
normal
density
and
texture
on
x-ray
examination.
As
localized
bone
involvement
by
infection
usually'
does
not
give
rise
to
general
metabolic
disturbances,
the
patient
may
be
regarded
as
a
control
for
the
present
purpose.
He
was
given
Diets
1,
2
and
3
in
that
sequence.
With
each
diet,
namely,
with
each
level
of
phos-
TABLE
I
Composition
of
diets
in
grams
per
day
t
t
Calcium,
phosphorus
and
nitrogen
values
are
actually
determined,
and
vitamin
D
values
taken
from
Wu
(8);
+
good
amount;
+
fair
amount;
±
no
appreciable
amount;
*
doubtful
or
undetermined.
Approximate
computation
of
the
acid
base
balance
of
the
diets
according
to
Sherman
(9)
gives
potential
acidities
ranging
from
19
to
35
cc.
of
normal
acid
for
Subject
1,
and
30
to
44
cc.
for
Subject
2.
CALCIUM
AND
PHOSPHORUS
METABOLISM
IN
OSTEOMALACIA.
V
605
phorus
intake,
calcium
was
raised
by the
addition
of
desired
amounts
of
calcium
lactate.
With
this
patient,
3
levels
each
of
calcium
and
phosphorus
were
studied,
giving
9
combinations.
No
vitamin
D
was
administered.
Calculation
6f
the
acid
base
balance
of
the
diets
according
to
Sherman
(9)
showed
that
all
the
diets
were
potentially
acid
with
relatively
small
variations,
but
the
computation
should
be
consid-
ered
only
approximate,
because
of
'the
uncertainty
of
the
applicability
of
Sherman's
figures
to
local
foodstuffs.
Stool
and
urine
respectively
of
each
period
were
pooled
for
analysis.
Venepuncture
was
done
be-
f
ore
breakfast
at
the
beginning
of
each
period.
Metabolic
ward
routine
and
analytical
methods
for
calcium,
phosphorus
and
nitrogen
of
food,
urine,
stool
and
blood
were
described
previously
(7).
RESULTS
Serum
calcium
and
phosphorus.
As
seen
from
Figure
1,
Subject
1
maintained
a
fairly
stationary
level
of
serum
calcium
throughout
the
period
of
212
days
of
continuous
observation,
the
range
be-
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FIG.
I.
CALCIUM
AND
PHOSPHORUS
METABOLISM
AND
THEIR
SERUM
LEVELS
IN
RELATION
TO
VARYING
INTAKE
OF
CALCIUM
AND
PHOSPHORUS
IN
SUBJECT
1
606
S.
H.
LIU,
C.
C.
SU,
S.
K.
CHOU,
H.
I.
CHU,
C.
W.
WANG
AND
K.
P.
CHANG
ing
from
8.7
to
9.6
mgm.
per
100
cc.
and
the
trend
bearing
no
apparent
relation
to
the
dietary
changes.
The
serum
inorganic
phosphorus
level,
however,
varied
from
2.9
to
5.3,
a
difference
of
2.4
mgm.
per
100
cc.
The
phosphorus
level,
be-
ginning
at
4.3
mgm.
per
100
cc.,
gradually
went
down
to
3.0
as
calcium
intake
in
the
diet
was
stepped
up
to
1.7
grams
(
Period
4)
.
While
the
calcium
intake
was
maintained
at
this
high
level,
the
phosphorus
curve
began
to
climb
as
vitamin
D
was
given,
and
rose
to
a
maximum
of
5.3
as
the
phosphorus
intake
was
progressively
raised
(
Pe-
riod
15)
.
The
phosphorus
curve
showed
a
sec-
ond
drop
in
Periods
18
to
20
when
the
phosphorus
intake
was
suddenly
decreased
to
a
minimum,
and
a
subsequent
recovery
to
the
high
level
in
Periods
27
to
29
when
high
phosphorus
intake
was
re-
stored.
When
calcium
intake
was
maintained
at
a
lower
level,
namely,
1.0
gram
as
in
Periods
30
to
41,
similar
changes
in
the
phosphorus
intake
brought
about
a
repetition
of
the
cycle
of
events
in
the
serum
phosphorus
curve,
but
to
a
lesser
extent.
But
when
the
calcium
intake
was
kept
minimal
(Periods
42
to
53)
,
lowering
of
the
phosphorus
intake
failed
to
elicit
any
significant
change
in
serum
phosphorus.
In
other
words,
serum
phosphorus
varied
more
with
the
ratio
of
calcium
to
phosphorus
than
with
their
actual
levels
in
the
intake.
Whenever
the
ratio
is
high
serum
phosphorus
drops.
In
Subject
2
(Figure
2)
the
serum
calcium
level
was
also
relatively
constant,
varying
from
a
mini-
mum
of
9.0
to
a
maximum
of
10.2
mgm.
per
100
cc.,
irrespective
of
the
calcium
and
phosphorus
intake.
The
serum
phosphorus,
compared
with
that
of
Subject
1,
showed
much
less
fluctuation,
ranging
as
it
did
between
3.9
and
5.1
mgm.
per
100
cc.
Moreover,
the
trend
of
variation
with
dietary
intake
seemed
to
be
opposite
in
direction
to
that
seen
in
Case
1.
When
the
calcium
supply
was
short
in
relation
to
phosphorus
(low
Ca
:
P
ratio),
the
serum
phosphorus
tended
to
fall
with
a
subsequent
rise
when
calcium
intake
was
stepwise
increased.
However,
the
changes
observed
were
not
sufficiently
pronounced
to
render
their
signifi-
cance
indubitable.
From
the
above
observations
it
may
be
con-
cluded
that
dietary
variations
of
calcium
and
phos-
phorus
are
not
significantly
reflected
in
the
serum
calcium
level.
This
is
true
in
osteomalacia,
as
LEdrENOS-
.4
-
Is4TAKM.
&aft's
,
sys
Siva.
erMair
is
Mole
1.1
-11-4.1••••
milky
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sum
'&5676
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9ot,
Azi
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1419a.21212pigassi
FIG.
2.
CALCIUM
AND
PHOSPHORUS
METABOLISM
AND
THEIR
SERUM
LEVELS
IN
RELATION
TO
VARYING
INTAKE
OF
CALCIUM
AND
PHOSPHORUS
IN
SUBJECT
2
well
as
in
the
control
case,
probably
on
account
of
the
protective
influence
of
vitamin
D,
as
in
its
absence
the
serum
calcium
-
and
inorganic
phos-
phorus
reflect
remarkably
the
ratio
of
these
ele-
ments
in
the
diet
as
shown
by
Shohl
(10)
in
ex-
perimental
rickets
in
rats.
Dietary
changes
may
cause
fluctuations
in
serum
phosphorus,
however,
even
when
vitamin
D
is
added
to
the
diet.
In
healing
osteomalacia,
for
example,
where
there
is
marked
deposition
of
calcium
and
phosphorus
in
the
bones,
a
deficiency
in
intake
of
phosphorus
relative
to
calcium
intake
results
in
a
fall
in
serum
phosphorus
;
and
excess
phosphorus
intake
rela-
Cu
IS
.
Aof.
Synous
-
op
z
goo
'
Intake
Balances
Output
mgm.
0
5
19
7
6
209
31
4
19
77
6
8
6
3
4
1
4
1.39
1.93
3.05
2.12
2.94
2.67
2.50
3.49
3.44
5.50
3.13
2.00
Period
number
Diet
number
Ratio
Ca
:
P
Urinary
Ca
P
Dry
weight
P
cor-
rected
Ratio
Ca
:
P
corrected
Fecal
Ca
P
Ca
P
Ns
1
1
2
3
4
5
2
3
4
5
2
3
4
5a
2
3
4
3-
5
*6-
8
9-11
12-14
15-17
18-20
21-23
24-26
27-29
30-32
33-35
36-38
39-41
42-44
45-47
48-50
51-53
mgm.
1738
1738
1740
1691
1681
1676
1640
1691
1681
976
940
994
981
141
140
194
181
mgm.
914
914
627
925
1163
324
627
925
1163
324
627
924
1163
259
627
924
1163
mgm.
222
190
25
62
297
23
85
238
393
37
252
413
528
184
436
593
744
grams
19.4
12.7
17.0
17.9
22.8
20.1
18.9
18.3
22.2
19.7
15.9
16.5
19.0
18.4
11.6
18.3
20.2
mgm.
294
777
759
862
846
522
639
752
702
313
389
451
435
27
58
64
40
mgm.
272
486
319
535
428
14
281
391
326
-
31
126
210
227
-
224
34
89
84
grams
1.05
1.43
1.22
2.24
2.40
0.98
0.71
1.56
2.17
1.59
0.22
2.17
1.50
-0.01
0.70
1.40
1.11
tsgm.
212
404
249
406
287
-
44
239
301
201
-
124
113
82
139
-
223
-
6
7
20
1.90
1.90
2.14
1.83
1.45
5.18
2.60
1.83
1.45
3.01
1.50
1.08
0.84
0.54
0.22
0.21
0.16
Ca
mgm.
1444
956
962
822
829
945
970
935
960
582
545
535
540
111
78
129
137
P
mgm.
420
238
283
328
438
287
261
296
444
318
249
301
408
299
157
242
335
CALCIUM
AND
PHOSPHORUS
METABOLISM
IN
OSTEOMALACIA.
V
607
tive
to
calcium
intake
may
result
in
a
rise
in
serum
phosphorus.
On
the
other
hand,
in
the
case
of
localized
bone
disease
and
presumably
in
normal
individuals
where
excesses
in
supply
are
excreted
and
deficiencies
in
intake
are
made
up
from
the
large
skeletal
store,
serum
phosphorus
level
is
less
subject
to
fluctuation.
Paths
of
excretion.
The
data
from
Subject
1
as
presented
in
Figure
1
and
as
averaged
in
Table
II
demonstrate
a
general
reciprocal
relationship
between
urinary
calcium
and
phosphorus.
At
a
constant
level
of
calcium
intake,
progressive
in-
crement
of
phosphorus
supply
tended
to
decrease
the
urinary
calcium
sometimes
to
the
point
of
disappearance,
and
at
the
same
time
to
augment
the
urinary
phosphorus.
If
the
results
at
the
same
level
of
dietary
phos-
phorus
are
taken
for
comparison
successive
addi-
tion
of
calcium
intake
increased
the
urinary
cal-
cium
coincident
with
a
gradual
and
steady
diminu-
tion
of
urinary
phosphorus.
In
general,
the
mag-
nitude
of
urinary
excretion
of
calcium
was
small
or
negligible
but
it
became
considerable
when
cal-
cium
was
supplied
far
in
excess
of
the
dietary
phosphorus
(Periods
18
to
20).
Likewise,
uri-
nary
excretion
of
phosphorus
was
very
much
limi-
ted
on
low
phosphorus
diet,
but
became
dominant
when
phosphorus
supply
was
far
in
excess
of
dietary
calcium
(Periods
51
to
53).
Fecal
calcium
increased
consistently
with
the
calcium
intake,
having
little
relation
with
the
phos-
phorus
supply,
while
fecal
phosphorus
was
di-
rectly
related
not
only
with
dietary
phosphorus,
but
also
with
dietary
calcium.
Intestinal
elimina-
tion
of
phosphorus,
then,
depends
not
only
on
its
supply
in
the
diet,
but
also
on
the
amount
of
cal-
cium
presented
in
the
intestine
for
excretion.
In
Subject
2
(Figure
2
and
Table
III)
similar
results
were
obtained.
The
magnitude
of
urinary
calcium
excretion
was
greater,
and
it
never
dis-
appeared,
even
when
the
supply
was
minimal
in
the
presence
of
large
'phosphorus
intake
(Periods
19
to
21).
Likewise,
when
phosphorus
intake
was
minimal
in
the
presence
of
excessive
dietary
calcium,
urinary
phosphorus,
though
decreased,
was
still
considerable,
compared
with
that
in
heal-
ing
osteomalacia.
The
fecal
elimination
of
cal-
cium
and,
to
a
lesser
degree,
of
phosphorus
in
Subject
2
was
greater
also,
but
the
'correlation
be-
tween
the
intake
of
calcium
and
phosphorus
and
their
output
in
the
stool
was
just
as
close.
In
addition
to
the
tendency
for
fecal
phosphorus
to
vary
directly
with
calcium
intake,
there
was
a
TABLE
II
Subject
I.
Average
daily
calcium
and
phosphorus
metabolism
*
Vigantol
1
cc.
daily
started
from
this
period
and
continued
throughout.
608
S.
H.
LIU,
C.
C.
SU,
S.
K.
CHOU,
H.
I.
CHU,
C.
W.
WANG
AND
K.
P.
CHANG
TABLE
III
Subject
2.
Average
daily
calcium
and
phosphorus
metabolism
Intake
Balances
Output
Ca
P
P
Period
number
Diet
number
Urinary
Ratio
Ca
:P
Ca
P
Fecal
P
Ca
Dry
weight
P
corrected
1-
3
4-
6
7-
9
10-12
13-15
16-18
19-21
22-24
25-27
mgm.
178
1058
2043
118
1023
2080
173
1078
2084
grams
20.3
20.5
18.2
16.5
21.4
21.2
21.0
20.7
25.4
mgm.
28
89
115
-
14
-23
42
-
72
83
155
mgm.
1.65
2.27
2.33
1.16
1.09
1.16
0.60
0.50
0.48
mgm.
-
69
-
45
-
22
-
82
-
87
-
26
-107
54
127
mgm.
402
402
402
582
582
582
1094
1094
1094
0.44
2.63
5.08
0.20
1.76
3.58
0.16
0.99
1.91
1
1
1
2
2
2
3
3
3
mgm.
73
189
252
79
153
211
19
36
116
mgm.
232
158
104
341
282
221
695
519
414
mgm.
153
155
183
255
323
319
471
492
525
mgm.
-
102
133
230
-
202
58
374
-
219
183
156
Ca
mgm.
207
736
1561
241
928
1495
373
859
1812
discernible
but
slight
tendency
for
the
fecal
cal-
cium
to
vary
directly
with
phosphorus
intake.
As
the
average
daily
dry
fecal
weights
in
both
cases
varied
only
slightly
on
the
various
diets,
it
is
unlikely
that
variations
in
roughage
were
suffi-
ciently
large
to
play
an
important
role
in
the
in-
testinal'
elimination
of
calcium
and
phosphorus.
Balances.
While
calcium
balance
may
be
taken
to
represent
the
state
of
bone
metabolism,
phos-
phorus
balance
is
under
the
dual
influence
of
bone
and
soft
tissue
metabolism.
For
every
17
grams
of
nitrogen
retained
or
lost,
1
gram
of
phosphorus
is
retained
or
lost.
To
calculate
the
amount
of
phosphorus
actually
involved
with
calcium
in
bone
metabolism,
the
total
phosphorus
balance
is
cor-
rected
by
an
amount
equivalent
to
nitrogen
bal-
ance.
The
corrected
phosphorus
balances
are
set
forth
in
Tables
II
and
III.
In
Table
II
it
may
be
of
interest
to
note
the
remarkable
effect
of
vita-
min
D
on
calcium
balance
in
osteomalacia.
Prior
to
vitamin
D
administration
the
patient
retained
294
mgm.
of
calcium
on
an
intake
of
1738
mgm.
per
day
(Periods
3
to
5),
but
after
its
administra-
tion
the
retention
increased
to
777
mgm.
on
'the
same
intake
(Periods
6
to
8),
the
improvement
being
mainly
due
to
lessened
elimination
in
the
stool.
To
facilitate
comparison,
Tables
IV
and
V
are
constructed
in
which
calcium
and
corrected
phos-
phorus
balances
are
grouped
according
to
intake.
Subject
1
(as
seen
in
the
upper part
of
Table
IV)
exhibited
a
striking
dependence
of
calcium
balance
on
calcium
intake.
Calcium
retention
on
the
aver-
age
increased
steadily
from
47
to
654
mgm.
per
day
as
calcium
intake
was
progressively
raised
from
164
to
1672
mgm.
per
day,
regardless
of
phosphorus
intake.
On
the
other
hand,
at
a
given
TABLE
IV
Subject
I.
The
effect
of
calcium
and
phosphorus
intake
on
their
balances
Calcium
Calcium
balance
at
the
phosphorus
intake
intake
of
Range
mgm.
0.16
40
1.08
451
2.60
639
Average
of
Ca
balance
at
same
P
intake
regard-
less
of
Ca
intake
Calcium
intake
Phosphorus
balance
at
the
phos-
phorus
intake
of
324
627
922
1163
mgm.
mgm.
mgm.
mgm.
0.52
0.22
0.21
0.16
-223
-6
7
20
-50
8.01
1.50
1.08
0.84
-124
113
82
139
6.18
8.60
239
1.88
301
45
1.
-44
239
301
201
Average
P
bal-
ance
at
same
P
intake
regardless
of
Ca
intake
*
Figures
in
italics
are
ratios
of
calcium
to
phosphorus
intake.
1640-1691
1640-1691
940-994
mgm.
140-194
940-994
140-194
Range
Level
mgm.
164
Level
1672
1672
973
973
164
mgm.
0.52*
27
8.01
313
5.18
522
324
mgm.
-130
287
627
mgm.
mgm.
0.22
58
1.60
389
362
115
922
mgm.
mgm.
0.21
64
1.88
752
422
130
120
0.84
435
1.45
702
1163
mgm.
392
Average
Ca
balance
at
same
Ca
intake
re-
gardless
of
P
intake
Average
P
balance
at
same
Ca
intake
re-
gardless
of
P
intake
mgm.
47
397
654
52
174
CALCIUM
AND
PHOSPHORUS
METABOLISM
IN
OSTEOMALACIA.
V
609
level
of
calcium
intake,
progressive
increment
of
dietary
phosphorus
up
to
922
mgm.
per
day
re-
sulted
in
a
slight
ascending
tendency
in
the
cal-
cium
balance,
but
further
increase
to
1163
mgm.
failed
to
improve
the
calcium
balance
which,
in
fact,
f
ell
somewhat
at
the
latter
level
of
phos-
phorus
intake.
Corrected
phosphorus
balance
likewise
depended
more
on
calcium
than
on
phos-
phorus
intake.
When
calcium
intake
was
raised
from
164
to
1672
mgm.,
the
average
phosphorus
balance
increased
from
50
to
174
mgm.
;
whereas
various
levels
of
phosphorus
intake
made
no
striking
difference
to
the
phosphorus
balance
except
in
the
case
of
minimal
phosphorus
intake
where
negative
balance
prevailed.
Balance
data
on
Subject
2,
summarized
in
Ta-
ble
V,
show
essentially
the
same
findings,
namely,
the
greater
importance
of
calcium
as
the
limiting
factor
in
both
calcium
and
phosphorus
balances.
However,
on
a
minimal
calcium
intake
of
145
mgm.
he
lost
on
the
average
174
mgm.
per
day
in
TABLE
V
Subject
2.
The
effect
of
calcium
and
phosphorus
intake
on
their
balances
Average
Ca
balance
at
same
Ca
intake
re-
mgm.
1094
gardless
of
P
intake
mgm.
0.44*
—102
2.63
113
6.08
230
Average
Ca
balance
at
same
P
intake
re-
gardless
of
Ca
intake
Calcium
Phosphorus
balance
at
the
intake
phosphorus
intake
of
Level
mgm.
mgm. mgm.
402
582
1094
0.44
0.20
0.18
69
—82
—107
2.63
1.78
0.99
45
—87
54
6.08
3.68
1.91
22
—26
126
26
Average
P
balance
at
same
P
intake
re-
—45
—65
24
gardless
of
Ca
intake
*Figures
in
italics
are
ratios
of
calcium
to
phosphorus
intake.
contrast
to
Subject
1
who
gained
47
mgm.
on
an
intake
of
164
mgm.
The
degree
of
calcium
loss
on
a
minimal
intake
in
Subject
2
was
within
nor-
mal
limits
(11),
while
the
behavior
of
Subject
1
was
usually
conservative.
Thus
the
latter
stored
approximately
95
grams
of
calcium
and
43
grams
of
phosphorus
in
the
period
of
200
days,
equiva-
lent
to
15
per
cent
of
the
stores
which
should
be
in
the
body,
in
contrast
to
the
control
patient
who
retained
only
5.9
grams
of
calcium
and
4.8
grams
of
phosphorus
in
108
days.
Examination
of
the
ratios
of
calcium
to
cor-
rected
phosphorus
balance
(Table
II)
shows
that
they
are
above
2
in
the
majority
of
instances,
and.
above
3
in
several
instances,
bearing
no
close
rela-
tionship
with
the
ratios
of
intake.
If
we
accept
the
'mineral
composition
of
normal
bone
as
CaCO
3
.2Ca
2
(
PO
4
)
2
according
to
the
x-ray
analy-
sis
of
Roseberry,
Hastings
and
Morse
(12),
then
the
ratio
of
Ca
:
P
should
be
2.26.
The
fact
that
the
ratios
of
retention
in
Subject
1
were
usually
higher
than
that
prescribed
for
normal
bone
would
suggest
that
more
calcium
was
deposited
as
CaCO
3
than
Ca
2
(PO
4
)
2
in
the
new
bone
forma-
tion
or
'that
calcium
suffered
to
a
greater
extent
than
phosphorus
during
the
prior
demineraliza-
tion.
As
to
the
actual
amount
of
calcium
re-
tained,
the
maximum
was
752
mgm.
(or
45
per
cent
of
intake)
on
an
intake
of
1672
mgm.
calcium
and
922
mgm.
phosphorus
giving
a
ratio
of
1.83
(Table
IV).
This
happens
to
be
also
the
level
and
ratio
of
intake
associated
with
the
largest
re-
tention
of
phosphorus,
namely,
301
mgm.
(or
32
per
cent
of
intake).
Thus
both
calcium
and
phos-
phorus
have
to
be
given
at
fairly
high
levels
with
a
ratio
approaching
2
in
order
to
secure
maximal
retention
of
both
elements.
Otherwise,
the
ratio
made
very
little
difference
to
the
calcium
balance
which
'depended
mainly
on
the
level
of
intake,
in
conformity
with
the
work
of
Shohl
(10).
DISCUSSION
The
present
results
obtained
with
the
patient
with
osteomalacia
receiving
continuous
admin-
istration
of
vitamin
D
are
in
entire
agreement
with
those
of
previous
studies
on
patients
whose
treat-
ment
with
vitamin
D
was
discontinued
after
rela-
tively
short
periods
of
4
to
6
weeks
when
its
maxi-
mum
effect
had
been
attained.
The
behavior
of
2012-2084
1012-1078
2012-2084
1012-1078
mgm.
112-178
112-178
Range
Range
Calcium
intake
Level
mgm.
145
2055
1040
2055
1040
145
Calcium
balance
at
the
phos-
phorus
intake
of
402
mgm.
87
582
mgm.
mgm.
0.20
—202
3.58
374
1.76
—58
38
mgm.
0.18
—219
0.99
183
1.91
156
40
Average
P
balance
at
same
Ca
intake
re-
gardless
of
P
intake
mgm.
—174
—86
—26
253
86
610
S.
H.
LIU,
C.
C.
SU,
S.
K.
CHOU,
H.
I.
CHU,
C.
W.
WANG
AND
K.
P.
CHANG
serum
calcium
and
phosphorus,
the
manner
of
conservation
of
these
elements
through
the
uri-
nary
and
intestinal
tracts,
the
ability
of
the
pa-
tients
to
maintain
positive
calcium
balance
on
minimal
intake
and
to
retain
large
amounts
of
it
on
higher
levels
of
intake,
and
finally
the
relatively
greater
importance
of
calcium
intake
rather
than
phosphorus
intake
as
the
limiting
factor
in
both
calcium
and
phosphorus
'retention
are
essentially
the
same
in
both
instances.
Thus
vitamin
D,
once
given
to
the
extent
of
its
maximum
effect,
will
maintain
its
action
unabated
for
at
least
eral
months
after
its
discontinuation,
and
its
con-
tinuous
administration
in
the
treatment
of
osteo-
malacia
does
not
seem
to
offer
any
substantial
advantage.
In
the
therapy
of
osteomalacia,
while
vitamin
D
administration
corrects
the
basic
metabolic
defect,
it
is
essential
that
both
calcium
and
phosphorus
be
given
at
fairly
high
levels,
preferably
with
a
ratio
of
approximately
2
in
order
to
promote
large
re-
tention
of
both
elements
and
tlref
ore
rapid
restoration
of
the
mineral
contents
of
the
de-
pleted
osseous
system.
With
ordinary
Chinese
dietaries
which
are
low
in
calcium
and
fairly
high
in
phosphorus,
the
desired
high
level
of
calcium
intake
has
to
be
supplied
as
calcium
salts,
while
that
of
phosphorus
intake
can
easily
be
taken
care
of
by
the
diet.
The
behavior
of
the
patient
without
skeletal
de-
calcification
resembles
that
of
patients
having
heal-
ing
osteomalacia
in
respect
to
the
reciprocal
rela-
tionship
between
urinary
calcium
and
phosphorus,
the
approximately
parallel
relationship
between
stool
calcium
and
phosphorus,
the
dependence
of
both
calcium
and
phosphorus
balances
on
calcium
intake,
and
the
slight
effect
of
phosphorus
intake
as
a
limiting
factor
in
both
calcium
and
phos-
phorus
retention.
On
the
other
hand,
he
differs
in
that
the
serum
phosphorus
is
relatively
more
stable
toward
dietary
changes,
and
in
that
the
magnitudes
of
urinary
and
stool
excretion
of
cal-
cium
and
phosphorus
are
greater,
resulting
in
negative
balance
on
low
intake
and
only
slight
retention
on
higher
levels
of
intake.
These
dif-
ferences
are
but
an
expression
of
the
fact
that
in
a
relatively
normal
individual
measures
of
min-
eral
conservation
are
less
urgently
in
need
of
ap-
plication.
SUMMARY
1.
In
two
patients,
one
with
osteomalacia
under
reparation
and
the
other
with
syphilitic
osteitis
of
radius
and
tibia,
the
serum
levels
of
calcium
and
phosphorus,
paths
of
excretion
and
retention
of
these
elements
were
studied
in
relation
to
their
levels
and
ratios
of
intake.
2.
Serum
calcium
was
fairly
constant
in
both
cases,
while
serum
inorganic
phosphorus
tended
to
lower
with
a
higher
ratio
of
Ca
:
P
intake
in
the
first
patient.
No
such
variations
were
demon-
strable
in
the
second
patient.
3.
A
reciprocal
relationship
between
calcium
and
phosphorus
in
urine
was
shown
in
both
in-
stances.
Whenever
the
Ca
:
P
ratio
in
the
diet
was
high,
urinary
calcium
increased,
while
urinary
phosphorus
diminished.
An
opposite
change
in
the
ratio
resulted
in
a
diminution
of
urinary
cal-
cium
coinciding
with
a
rise
of
urinary
phosphorus.
4.
Fecal
calcium
and
phosphorus
varied
with
their
respective
level
of
intake,
while
fecal
phos-
phorus
was
also
partly
dependent
on
calcium
in-
take.
5.
Retention
of
either
calcium
or
phosphorus
depended
more
on
the
calcium
than
phosphorus
intake,
although
both
had
to
be
supplied
in
fairly
large
quantities
with
a
Ca
:
P
ratio
of
approxi-
mately
2
'in
order
to
realize
maximal
retention
of
both
elements
to
promote
efficient
repair
of
skele-
tal
demineralization
in
osteomalacia.
6.
The
present
study
with
prolonged
admin-
istration
of
vitamin
D
revealed
no
essential
dif-
ference
from
the
previous
work
with
limited
vita-
min
D
therapy,
showing
that
the
effect
of
vitamin
D
lasts
long
after
its
discontinuation.
CASE
HISTORIES
Case
1.
H.
F.
M.,
a
Chinese
housewife
of
32,
was ad-
mitted
on
August
28,
1935
for
pain
in
back
and
legs
and
difficulty
in
walking.
These
began
7
years
prior
to
ad-
mission
when
she
had
her
first
pregnancy.
Labor
was
spontaneous
but
lasted
for
more
than
24
hours.
After
that
she
had
periodical
exacerbations
of
the
above
symp-
toms
in
winter
and
spring
when
she
kept
herself
indoors.
The
second
pregnancy
occurred
4
years
after
the
first
and
resulted
in
a
seven
months'
premature
labor
lasting
more
than
48
hours.
Henceforth
symptoms
became
worse.
She
could
neither
stand
on
her
feet
nor
walk
without
support.
Her
diet
had
always
been
extremely
poor.
In
the
cold
months
she
lived
on
cereals
and
salted
vegetables,
In
the
warmer
months
some
fresh
vegetables
CALCIUM
AND
PHOSPHORUS
METABOLISM
IN
OSTEOMALACIA.
V
611
were
available.
Meat
was
seldom
taken
and
eggs
only
occasionally.
Examination
on
admission
confirmed
her
statement
about
her
inability
to
stand
or
walk
without
support.
Body
weight
was
40
kgm.
and
height
136
cm.
On
lying
down,
the
right
thigh
was
slightly
flexed
and
abducted,
with
the
knee
joint
held
in
30°
flexion.
Movement
at
the
hip
joint
caused
pain.
There
was
no
tenderness
along
the
lower
extremities.
The
pelvis
was
of
the
funnel
type.
Symphysis
pubis
protruded
and
sacrum
was
prominent.
Tenderness
was
marked
over
the
sacro-iliac
joints,
pelvic
bones,
lower
ribs
and
lumbar
vertebrae.
The
right
upper
molar
teeth
and
lower
incisors
were
loose.
Other
physi-
cal
findings
were
normal.
X-ray
showed
a
deformed
pelvis
and
general
osteoporosis
and
some
pleural
thicken-
ing
with
adhesions
in
the
right
lower
chest.
Blood
cal-
cium
was
8.92,
phosphorus
3.29
mgm.
per
cent,
and
plasma
phosphatase
4.9
units
(Bodansky).
Blood
counts
and
urinalysis
were
essentially
normal.
Stool
was
positive
for
ova
of
ascaris.
Metabolic
studies
were
carried
out
in
four-day
periods
for
212
days
from
October
4,
1935
to
May
2,
1936.
Besides
the
dietary
treatment
and
vitamin
D
administration
she
also
received
physiotherapy
in
the
form
of
exercises
for
extension
of
the
hip
and
spine
and
infra-red
irradiation.
At
the
time
of
discharge
she
could
walk
fairly
well
without
support,
and
x-ray
of
bones
re-
vealed
definitely
increased
density.
Case
2.
L.
Y.
S.,
a
Chinese
man
of
24,
entered
on July
13,
1934
for
swelling
and
lengthening
of
the
right
leg
of
8
years'
duration
and
of
the
right
forearm
of
two
years'
duration.
Onset
was
insidious
without
history
of
injury.
He
had
occasional
low
grade
fever
and
pain
after
pro-
longed
walking.
He
had
had
venereal
exposures.
The
patient
was
found
to
be
slightly
undernourished.
Body
weight
was
42.2
kgm.
and
height
159
cm.
His
right
leg
was
5.5
cm.
longer
than
the
left
and
also
bigger
espe-
cially
in
the
lower
part.
There
was
slight
tenderness
over
the
right
tibia,
and
the
overlying
skin
was
slightly
warmer
than
that
of
the
left
side.
The
knee
and
ankle
were
not
involved.
Right
'forearm
was
1.5
cm.
longer
than
the
left.
The
elbow
and
wrist
were
free.
Other
physical
findings
were
essentially
normal.
X-ray
of
the
bones
showed
irregular
areas
of
condensation
and
rare-
faction
in
the
cortex
involving
the
entire
length
of
right
tibia
and
radius.
The
rest
of
the
skeleton
appeared
nor-
mal.
Blood
and
urine
examinations
revealed
no
signifi-
cant
findings.
Stools
contained
ova
of
ascaris.
Blood
calcium
was
9.7
and
phosphorus
4.2
mgm.
per
cent.
Basal
metabolic
rate
was
+
8.4
per
cent.
Blood
Wassermann
and
Kahn
tests
were
strongly
positive.
Metabolic
studies
were
carried
on
for
108
days
(27
four-day
periods
from
September
18,
1934
to
January
3,
1935).
Subsequent
in-
tensive
antisyphilitic
treatment
to
date
has
given
rise
to
marked
improvemerit
in
the
bone
lesions.
BIBLIOGRAPHY
1.
Maxwell,
J.
P.,
Osteomalacia
in
China.
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M.
J.,
1923,
37,
625.
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Maxwell,
J.
P.,
Further
studies
in
osteomalacia.
Proc.
Roy.
Soc.
Med.
(Section
Obst.
and
Gynec.),
1930,
23,
19.
3.
Maxwell,
J.
P.,
and
Miles,
L.
M.,
Osteomalacia
in
China.
J.
Obst.
and
Gynec.
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Emp.,
1925,
32,
433.
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Hannon,
R.
R.,
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Chu,
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I.,
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S.
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phos-
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of
vitamin
D
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its
apparent
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Med.
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1934,
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Wu,
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ef-
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of
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levels
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ratios
of
intake
of
cal-
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phosphorus
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their
serum
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Wu,
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Sherman,
H.
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of
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and
Nutrition.
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New
York,
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Shohl,
A.
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in
rats.
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The
effect
of
low
calcium-high
phosphorus
diets
at
various
levels
and
ratios
upon
the
production
of
rickets
and
tetany.
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a
low
cal-
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