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Calcium Effects on Phosphorus Absorption:
Implications for the Prevention and Co-Therapy of
Osteoporosis
a
b
Robert P. Heaney MD, FACN & B. E. C. Nordin MD
a
Creighton University, Omaha, Nebraska (R.P.H.)
b
Institute of Medical & Veterinary Science, Adelaide, South Australia, AUSTRALIA
B.E.C.N.)
(
Published online: 24 Jun 2013.
To cite this article: Robert P. Heaney MD, FACN & B. E. C. Nordin MD (2002) Calcium Effects on Phosphorus Absorption:
Implications for the Prevention and Co-Therapy of Osteoporosis, Journal of the American College of Nutrition, 21:3,
239-244, DOI: 10.1080/07315724.2002.10719216
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Original Research
Calcium Effects on Phosphorus Absorption: Implications
for the Prevention and Co-Therapy of Osteoporosis
Robert P. Heaney, MD, FACN, and B. E. C. Nordin, MD
Creighton University, Omaha, Nebraska (R.P.H.), Institute of Medical & Veterinary Science, Adelaide, South Australia,
AUSTRALIA (B.E.C.N.)
Key words: calcium intake, phosphorus absorption, osteoporosis, osteoporosis therapy, calcium supplements, calcium
carbonate, calcium phosphate
Objective: To evaluate the effect of calcium intake on absorption of dietary phosphorus, with special
reference to typical calcium intakes and to those likely to be encountered in prevention and treatment of
osteoporosis.
Setting: Two academic health sciences centers; inpatient metabolic research unit.
Methods: Evaluation of calcium and phosphorus balance data obtained in two data sets, the first, 543 studies
of healthy women aged 35–65, and the second, 93 men and women aged 19–78; development of multiple
regression models predicting fecal phosphorus (the complement of net absorbed phosphorus); data from the two
centers analyzed separately as a check on the consistency of the findings.
Results: Mean net absorption of phosphorus was 60.3% (Ϯ18.1) for data set 1 and 53.0% (Ϯ9.4) for data
set 2. Just two variables, fecal calcium and diet phosphorus, were positively and independently associated with
fecal phosphorus. These variables explained 73% of the variance in fecal phosphorus in data set 1 and 33% in
data set 2. Fecal calcium alone explained the lion’s share of the relationship. The coefficients of the fecal calcium
term in the models fitted to the data were 0.332 Ϯ 0.022 and 0.155 Ϯ 0.039, for data sets 1 and 2, respectively.
Adjusting for the relationship between fecal calcium and calcium intake and using the parameters of the larger
data set, it follows that each increase in calcium intake of 0.5 g (12.5 mmol) decreases phosphorus absorption
by 0.166 g (5.4 mmol).
Conclusions: As calcium intake increases without a corresponding increase in phosphorus intake, phospho-
rus absorption falls and the risk of phosphorus insufficiency rises. Intakes with high Ca:P ratios can occur with
use of supplements or food fortificants consisting of non-phosphate calcium salts. Older patients with osteopo-
rosis treated with current generation bone active agents should receive at least some of their calcium co-therapy
in the form of a calcium phosphate preparation.
importance or magnitude clear for the substantially lower
dose calcium supplementation employed as co-therapy for
INTRODUCTION
In recent years two calcium salts (carbonate and acetate),
used in large doses, have largely replaced aluminum hydroxide
preparations for control of phosphorus absorption in patients
with end-stage renal disease. The effect, as with the alumi-
num compounds, is based on the fact that calcium complexes
with phosphate in the intestinal lumen and thereby reduces
its absorption. The interaction has not been well quantified
even at the high doses used in renal failure patients, nor is its
osteoporosis.
Two facts suggest that it may be important to examine
calcium’s effects on phosphorus absorption under these cir-
cumstances. First is the emergence of therapies for osteoporosis
that require high dose co-therapy with calcium in order to
achieve their potential increase in bone mineral density [1–3],
and, second, such therapies are often concentrated in elderly
patients who tend to have the lowest food phosphorus intakes
Work supported in part by NIH AR07912 and by Health Future Foundation.
th
Address reprint requests to: Robert P. Heaney, MD, FACN, Creighton University, 601 N. 30 Street—Suite 4841, Omaha, Nebraska 68131. E-mail: rheaney@
creighton.edu
Journal of the American College of Nutrition, Vol. 21, No. 3, 239–244 (2002)
Published by the American College of Nutrition
2
39

Calcium Effects on Phosphorus Absorption
[
4]. Reduction of absorption of diet phosphorus in such indi-
calcium and phosphorus content, and those values were in-
cluded in the total intake of the nutrients concerned.
The methods for data set 2 were similar except that each
balance study extended over two weeks, the first week for
equilibration, and the second week for daily fecal collections.
The diets were the same every day during this two-week period,
and polyethylene glycol was fed from day 1 and used as a
non-absorbable fecal marker.
viduals could produce a lowering of serum phosphate concen-
tration that would both augment osteoclastic bone resorption
[5] and interfere with osteoblast work efficiency [6].
To evaluate this potential for an unintended harmful effect
of calcium co-therapy, we turned to our respective databases of
calcium and phosphorus balance measurements in an attempt to
quantify the extent to which luminal calcium affects phospho-
rus absorption in the range of normal intakes and to develop the
parameters of any such relationship so as to estimate the risk in
patients being treated with current generation bone active
agents.
Analytical Methods and Statistical Analysis
The analytical methods have all been described in detail
elsewhere [7–10]. Data were characterized by standard descrip-
tive statistics using a variety of packages [SPSS for Windows
(SPSS, Chicago, IL) and Excel (Microsoft, Redmond, WA)].
METHODS
Multiple linear regression models were developed using SPSS.
Some of the subjects in both sets were studied more than once
over the 25-year period involved (mean 2.4 times in data set 1),
and their data are treated in this analysis as if they were indepen-
dent observations. This approach is justified by the fact that there
was substantial within-subject drift in dietary intake patterns,
absorption efficiencies and hormonal status over the period of the
several studies, and the within-individual variance was not appre-
ciably different from the between-individual variance with respect
to the variables of interest. Data set 2 was used mainly to test
whether the relationships observed in data set 1 could be con-
firmed in an independently studied group of individuals.
Subjects
Subjects in data set 1 were 191 Roman Catholic nuns
studied from 1967 through 1992 as inpatients on a metabolic
research unit. Their ages ranged from 35 to 65 at the time of
study. Most were studied several times at five-year intervals.
Together they contributed 470 measurement sets to this anal-
ysis. The subjects have been extensively characterized else-
where [7]. When routine work-up revealed concurrent medical
conditions that might interfere with calcium metabolism during
a particular study, the data for such a study were eliminated
from this analysis. The subjects each gave written consent to
the project, and the Creighton University IRB approved the
project after it came into existence (well after the inauguration
of this study).
RESULTS
Subjects in data set 2 were a mixed group of 88 women and
five men, studied in Leeds, U.K. They, too, have been de-
scribed elsewhere [8, 9]. Many of the women in data set 2 were
taking calcium supplements during their balance measure-
ments, some with meals, but many at bedtime, while virtually
none of the subjects in data set 1 received supplements.
Table 1 sets forth the descriptive statistics with respect to
the relevant intake and output variables by data set. The mean
intakes of calcium and phosphorus in the women of data set 1
[0.696 and 1.101 g/day (17.4 and 35.5 mmol)] were very
similar to the NHANES-III median values for women 50–59
years of age. In data set 2, phosphorus intake was about the
same, but calcium intake was ϳ50% higher than in data set 1,
largely because of the use of non-phosphate calcium supple-
ments as a part of study protocols. The slope of fecal calcium
on calcium intake in these studies was 0.896 in data set 1 and
0.851 in data set 2 (weighted average: 0.890), indicating net
absorption of incremental calcium intakes in the range of 11%.
It is the unabsorbed calcium that would interact with phos-
phorus in the chyme, and its interference with phosphorus
absorption was explored with various multivariate models em-
ploying the variables listed in Table 1 (as well as several others,
not shown). The statistically best model, and the one that was
physiologically the most straightforward, related fecal phos-
phorus to fecal calcium and phosphorus intake. (Net absorbed
phosphorus, by definition, is given as phosphorus intake minus
fecal phosphorus). The parameters of the linear regression
equations are set forth in Table 2 for the two data sets sepa-
rately.
Protocol
Data set 1 was a longitudinal, observational, cohort design
and data set 2, cross-sectional. In data set 1, subjects completed
seven-day diet diaries prior to each admission to the metabolic
unit, and controlled diets were prepared for the eight-day in-
patient stay to match the self-selected intakes of nitrogen,
phosphorus and calcium of the subjects prior to admission. The
diet was constant throughout the stay, and all excreta were
collected and analyzed. Stool collections were timed and de-
marcated by the use of a nonabsorbable intake marker (poly-
ethylene glycol through most of the project duration), ingested
with each meal.
During the inpatient study, subjects maintained their usual
intake of medications, vitamin and mineral supplements, health
food preparations, etc. Each such product was analyzed for its
2
40
VOL. 21, NO. 3

Calcium Effects on Phosphorus Absorption
Table 1. Intake and Output Values for Calcium and Phosphorus*
Data Set 1
Mean
Data Set 2
S.D.
Mean
S.D.
Calcium intake
0.696 (17.4)
1.101 (35.5)
0.482
0.111 (2.78)
0.663 (21.4)
0.585 (14.6)
0.439 (14.2)
1.022
0.306 (7.65)
0.301 (9.7)
0.136
0.079 (2.0)
0.199 (6.4)
0.284 (7.1)
0.170 (5.5)
0.273
1.142 (28.6)
1.116 (36.0)
0.806
0.137 (3.4)
0.592 (19.1)
1.006 (25.2)
0.524 (16.9)
1.523
0.224 (5.6)
0.133 (4.3)
0.190
0.121 (3.0)
0.127 (4.1)
0.236 (5.9)
0.106 (3.4)
0.378
Phosphorus intake
Diet Ca:P (mol:mol)
Net absorption calcium
Net absorption phosphorus
Fecal calcium
Fecal phosphorus
Fecal Ca:P (mol:mol)
*
N ϭ 470 for all variables in Data Set 1 and 93 for Data Set 2; except for ratios, values are g/day (mmol/day).
Table 2. Parameters of the Regression Models for the Various Data Sets*†
Coefficient of Fecal
Ca Term
Coefficient of Diet
2
Data Set
N
Constant
R
P Term
1
2
470
96
0.023 (Ϫ0.011; ϩ0.055)
Ϫ0.053 (Ϫ0.229; ϩ0.123)
0.332 (0.288; 0.376)
0.155 (0.079; 0.232)
0.201 (0.159; 0.243)
0.377 (0.241; 0.512)
0.733
0.326
*
Mean (upper and lower bounds of 95% confidence interval); all values in grams.
The equation to which the data were fitted is as follows:
†
Fecal P ϭ Constant ϩ C
f p
* FecalCa ϩ C * DietP,
where C and C are the coefficients of the fecal Ca and diet P terms, respectively.
f
p
The strongest predictor of fecal phosphorus was not diet
phosphorus, as might have been expected, but unabsorbed diet
calcium (i.e., fecal calcium). Before including diet phosphorus
in the model in data set 1, for example, fecal calcium alone
(0.022), the upper confidence limit for the amount of phospho-
rus bound is only 210 mg (6.8 mmol) phosphorus per 500 mg
(12.5 mmol) calcium. Using this extreme value, the highest
plausible therapeutic calcium intake (e.g., 2.5 g/day–62.5
mmol) will bind up to 1.05 g (34 mmol) phosphorus. Con-
versely, the least amount plausibly bound at this high calcium
intake would be 0.61 g (19.7 mmol).
As can be seen in Table 3, at the 0.5 g (16 mmol) phos-
phorus intake level, net absorption is predicted to be negative at
calcium intakes above 1.0 g (25 mmol)/day, and would be close
to zero at the highest calcium intakes for even the 1.0 g (32
mmol) phosphorus intake. Such calculated negative absorption
figures for diets with high Ca:P ratios may not mean that
phosphorus is literally pulled out of the body. Rather they
indicate excess capacity to bind additional food phosphorus,
should it be ingested.
2
gave a value for R of 0.682. The data themselves in data set 1,
plus the plane defined by the least-squares regression model,
are presented in Fig. 1. The fit of the full model to the data was
2
extremely good (R ϭ 0.733). The fit of the data to a similar
model was less good for data set 2, although still highly
significant. This concordance serves as confirmation of the
general correctness of the model of data set 1.
Holding phosphorus intake constant and converting fecal
calcium to the corresponding intake value, one can calculate,
using the fecal calcium coefficient for data set 1, that each 0.5 g
(
12.5 mmol) increment in calcium intake increased fecal phos-
phorus (and therefore decreased phosphorus absorption) by
.166 g (5.4 mmol). Several worked examples of the predicted
0
interference in phosphorus absorption by calcium using the
parameters of data set 1, for various intakes of calcium and
phosphorus, are displayed in Table 3. However, given the
different intake Ca:P ratios of the two data sets, contrasting
their phosphorus absorption values shows this same effect
directly. Despite a slightly higher mean phosphorus intake in
the individuals of data set 2, as Table 1 displays, the subjects of
data set 2 absorbed an average of 0.071 g (2.3 mmol) less
phosphorus (p Ͻ 0.01). According to the models of Table 2,
this is best explained by their higher mean calcium intake [i.e.,
DISCUSSION
Phosphorus is not usually considered a problem nutrient. If
anything, it has been argued, there is an excess of phosphorus
in the food supply, at least in the U.S. [11–14]. The facts,
however, are not so clearly supportive of this conclusion [15].
In comparison with laboratory animals, in which the potential
harm of high phosphorus intakes has been mainly studied,
human phosphorus intake is low. Primate chows have a phos-
phorus density of ϳ5 mmol/100 kCal, rat chows range from
4–6 mmol/100 kCal, and dog chows contain ϳ9 mmol/100
kCal. By contrast, median phosphorus density in the U.S. diet
4
46 mg (11.1 mmol) higher].
Because the standard error of the coefficient of the fecal
calcium term for the model describing data set 1 is small
JOURNAL OF THE AMERICAN COLLEGE OF NUTRITION
241

Calcium Effects on Phosphorus Absorption
human parathyroid hormone 1–34) have the capacity to in-
crease central skeletal bone mineral density at a linear rate of
1
0% to 15% a year [1, 3]. This degree of bone building is the
largest an individual will have experienced since the adolescent
growth spurt, a life-stage when the phosphorus RDA in the U.S.
is 1250 mg (40 mmol/day), not the adult 700 mg figure. If one
takes 70% of the growth RDA as the critical intake value (i.e.,
1
250 ϫ 0.7 ϭ 875), one sees from Table 4 that more than half
of women over 80 years have intakes below this level, and
between 25 and 50% of women aged 60 to 80 years also have
phosphorus intakes that may be suboptimal for current anti-
osteoporosis agents.
Under such circumstances, absorbed phosphorus may be too
low to support both soft tissue phosphorus needs and new bone
mineralization (which consumes mineral at a Ca:P molar ratio
of ϳ1.6:1). Any induced phosphorus insufficiency under these
circumstances, expressed as a lowering of serum inorganic
phosphorus concentration, would not only limit bone gain, but
enhance osteoclastic bone resorption [5]—precisely opposite to
the direction toward which current anti-osteoporosis therapy is
pointed. Moreover, teriparatide, specifically, exerting its inher-
ent parathyroid hormone activity, would itself lower the renal
phosphorus threshold, thereby compounding the problem by
lowering serum inorganic phosphorus levels still further.
In the past, the principal source of calcium in the diet has
been dairy foods, which contain phosphorus as well as calcium.
Thus phosphorus intake tended to vary with calcium, and high
calcium intakes would not have affected phosphorus nutriture
adversely. However, increased awareness of the importance of
calcium, and the corresponding increase in supplement use,
coupled with widespread food fortification with calcium (most-
ly as non-phosphate calcium salts), have combined to change
the calcium intake distribution in adults appreciably, without
much effect on phosphorus intakes. Although precise quantifi-
cation of the current distribution of total calcium intakes re-
mains to be done (e.g., in the next NHANES), it is virtually
certain that supplements and fortification have raised Ca:P
intake ratios for the older age strata over the past few years.
The degree of interference reported here (ϳ166 mg phos-
phorus for every 500 mg ingested calcium—0.4 mmol phos-
phorus for every mmol calcium) is substantially less than might
have been predicted from simple stoichiometry. A 1:1 molar
Fig. 1. Three dimensional plot of fecal phosphorus as a function of diet
phosphorus and fecal calcium for the 470 balances of data set 1. The
diagonal plane through the data is the least squares fit according to the
parameters set forth in Table 2. In the equation inset, Z ϭ fecal P, X ϭ
fecal Ca, and Y ϭ diet P. (Copyright Robert P. Heaney, 2002. Used
with permission.)
is on the order of only 2 mmol/100 kCal [4]. And the most
recent adult RDA for phosphorus is 700 mg/day, which, for a
2
200 kCal energy intake, is only ϳ1 mmol/100 kCal [15].
The data of NHANES-III show that appreciable numbers of
individuals ingest less than 70% of even the adult RDA on
any given day [4], i.e., less than 490 mg/day. Thus the 0.5 g
phosphorus intake column in Table 3 is applicable to an appre-
ciable number of individuals. Table 4 lists the percentile distri-
bution of phosphorus intakes from NHANES-III, by age group,
for non-Hispanic, white U.S. women. As is clearly evident,
phosphorus intake is not normally distributed, and low phospho-
rus intakes, while found at all ages, are concentrated in the el-
derly. 15% of those 80 years and older and 10% of those 60 to
80 ingest less than 70% of the adult RDA on any given day.
But it is not certain that the adult RDA is the correct referent
for patients receiving current generation anti-osteoporosis ther-
apies. Bone active agents such as teriparatide (recombinant
Table 3. Calculated Net Phosphorus Absorption for Various Calcium and Phosphorus Intakes*
0
.5 g P/day (16 mmol)
1.0 g P/day (32 mmol)
1.5 g P/day (48 mmol)
Ca intake
Fecal P
NetAbsP†
Fecal P
NetAbsP†
Fecal P
NetAbsP†
0
1
1
2
2
.5 (12.5)
.0 (25)
.5 (37.5)
.0 (50)
0.271 (8.81)
0.419 (13.5)
0.567 (18.3)
0.714 (23.0)
0.862 (27.8)
0.229 (7.39)
0.081 (2.61)
Ϫ0.067 (Ϫ2.16)
Ϫ0.214 (Ϫ6.90)
Ϫ0.362 (Ϫ11.7)
0.372 (12.0)
0.519 (16.7)
0.667 (21.5)
0.815 (26.3)
0.963 (31.1)
0.628 (20.3)
0.481 (15.5)
0.333 (10.7)
0.185 (5.97)
0.037 (1.19)
0.472 (15.2)
0.620 (20.0)
0.768 (24.8)
0.915 (29.5)
1.063 (34.3)
1.028 (33.2)
0.880 (28.4)
0.732 (23.6)
0.585 (18.9)
0.437 (14.1)
.5 (62.5)
*
Using fecal Ca ϭ 0.89 (diet Ca); all values are from the parameters of the model for data set 1; all units are g (mmol).
†
Net absorption of phosphorus, i.e., phosphorus intake minus fecal phosphorus.
2
42
VOL. 21, NO. 3

Calcium Effects on Phosphorus Absorption
Table 4. Distribution of Phosphorus Intakes* in the U.S.†
Ages (years)
5th
10th
15th
25th
50th
75th
85th
90th
95th
3
4
5
6
7
8
0–39
0–49
0–59
0–69
0–79
0ϩ
434‡
486‡
451‡
399‡
415‡
353‡
581
575
525
482‡
478‡
431‡
677
634
596
586
550
761
764
739
727
679
581
1111
1027
976
998
902
1457
1341
1214
1299
1224
1157
1637
1564
1375
1497
1397
1286
1804
1650
1565
1735
1500
1435
2092
1797
1892
2183
1748
1686
486‡
833
*
†
‡
mg P/day.
Non-Hispanic, white women from NHANES-III (4).
Less than 70% adult RDA.
ratio for CaHPO would predict binding of 388 mg phosphorus
data, on the order of 0.2–0.24 mmol P/mmol Ca. These values
are lower than the values we report here (0.4:1), but the
confidence intervals of the several estimates overlap exten-
sively, and they do not differ significantly from one another.
Hence the models in Table 2 are at least directionally correct
when applied to intakes with high Ca:P ratios and may be
reasonably quantitative in that range as well. Moreover, the fact
that both of our data sets demonstrated interference in phos-
phorus absorption by unabsorbed digestate calcium reinforces
the finding of an effect.
4
by 500 mg calcium and, for Ca (PO ) at a Ca:P molar ratio of
3
4 2
1
.5:1.0, 258 mg phosphorus would be bound per 500 mg
calcium. A molar ratio of 1:1 seems more likely at digestate pH
values below 7.0. Even at the upper end of the confidence
interval for the regression model—210 mg (6.8 mmol)—bind-
ing would still be substantially less than the lowest stoichio-
metric prediction. This discrepancy may be partly due to rapid
absorption of phosphorus in the duodenum well before calcium
and phosphorus complexes can form in the chyme. In any event
it undoubtedly reflects the complexity and multiplicity of the
interactions within the digestive residue.
The data assembled in Fig. 1, derived from individuals
ingesting mainly unfortified, food-based diets, can be seen to
tend to cluster along a diagonal, with calcium and phosphorus
intakes varying together. 95% of the subjects had dietary Ca:P
molar ratios below 0.75:1.0 in data set 1 and below 1:1 in data
set 2. Accordingly, the data analyzed here provide only limited
information about phosphorus absorption at intakes with Ca:P
molar ratios substantially above 1:1. However, there are other
sources of information that bear on this high Ca:P region of the
intake space. One is the experience in patients with end-stage
renal disease, where high calcium intakes (as the carbonate or
acetate salts) do demonstrably block absorption of phosphorus
from diets with normal to low phosphorus contents. Nordin, in
his extensive review of nutritional phosphorus metabolism sev-
eral years ago [16], noted then that unabsorbed food calcium
lowers phosphorus absorption in normal subjects. And Spencer
et al. [17], in a series of metabolic balance studies, described a
The differences in the values for the coefficients in the
models for our two data sets are partly what would be expected
when a relationship observed in one group of data is checked in
an independent group. Partly also the differences are likely due
to the timing of calcium supplement use in the subjects of data
set 2 (bedtime), when interference with food calcium absorp-
tion would be reduced [18]. Such timing of calcium intake
would be expected to lower the value of the coefficient of the
fecal calcium term, precisely as observed in Table 2. That this
explanation is correct is suggested by a reanalysis of data set 2,
confined to those individuals with little or no calcium supple-
mentation. In such subjects, the coefficient of the fecal calcium
term is 0.283, not significantly different from that observed in
the studies of data set 1.
We hasten to stress, in conclusion, that none of this should
be taken to mean that the current trends toward increasing
calcium intake are harmful or that supplement use and judi-
cious calcium fortification of foods should be curtailed. As
recognized and documented at several levels over the past 20
years, calcium deficiency is perhaps the most prevalent nutrient
deficiency in the industrialized nations. Moreover, increasing
calcium intake, particularly in older individuals, results in
prompt and clinically important skeletal benefits [e.g., 19, 20].
Thus, with both supplementation and fortification, the issue
is not with the calcium itself, but with its accompanying anion.
One of the more dramatically effective trials of calcium sup-
plementation in the elderly employed tricalcium phosphate as
the calcium source [19], and the authors explicitly alluded to
the extra ingested phosphorus as perhaps partially responsible
for the strongly positive effect they produced. This suggestion
seems to have been largely ignored, both by the osteoporosis
2
5% reduction in phosphorus absorption in healthy individuals
with typical phosphorus intakes when calcium intake was in-
creased from 216 mg (5.4 mmol)/day to 2028 mg (50.7 mmol)/
day. Schiller et al. [18] reported ϳ60% reduction in net phos-
phorus absorption in normal individuals when a test meal was
coadministered with 25 mmol (1000 mg) calcium as the acetate
salt. The Ca:P intake ratio achieved by Spencer et al. was ϳ2:1
(mol:mol) and by Schiller et al., ϳ2.5:1 (mol:mol), much
higher than one could achieve using foods alone, but in a range
likely to be encountered as a part of current osteoporosis
therapy.
Phosphorus binding at the highest Ca:P ratios in Spencer et
al.’s data was ϳ0.09 mmol P/mmol Ca and in Schiller et al.’s
JOURNAL OF THE AMERICAN COLLEGE OF NUTRITION
243

Calcium Effects on Phosphorus Absorption
investigative community and by calcium supplement manufac-
turers.
4. Alaimo K, McDowell MA, Briefel RR, Bischof AM, Caughman
CR, Loria CM, Johnson CL: “Dietary Intake of Vitamins, Miner-
als, and Fiber of Persons 2 Months and Over in the United States:
Third National Health and Nutrition Examination Survey, Phase 1,
The dominant anions in the calcium supplement market
today, worldwide, are carbonate and citrate. Until recently the
anion probably would not have mattered. Given the calculated
phosphorus absorption effects of calcium in Table 3 and the
intake data of Table 4, it is likely that phosphorus intake is, in
fact, sufficiently high for most adults that the accompanying
anion does actually make little difference, i.e., it is calcium that
is mainly deficient in their diets, and the net effect of fortifi-
cation and supplementation is to bring calcium intake into
relative parity with other nutrients.
However, the same may not be true for many of the older
elderly nor for many of the patients requiring very high calcium
intakes as osteoporosis co-therapy. It would seem, therefore,
that such co-therapy should be in the form of one of the several
calcium phosphate salts. By the same reasoning, supplements
and calcium-fortified foods marketed specifically for older
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If the interference we describe here turns out to be clinically
significant, it would contribute to blunted responsiveness dur-
ing anti-osteoporosis therapy. The primary response variable
for groups of subjects will often be change in bone density. As
is generally recognized, this is an insensitive measure in indi-
viduals, and a poor response may thus be hard to detect.
However, suggestive evidence of a compromised response
would be low values for serum or urine phosphorus. Future
studies of high potency, bone-active agents should, perhaps,
incorporate provision for such measurement if they utilize a
non-phosphate calcium supplement. Additionally, physicians
seeking to interpret apparently weak bone density responses in
individual patients might get help from these inexpensive
checks on phosphorus status.
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Received November 28, 2001; revision accepted February 7,
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