Q0glocatedco pri in periodsBullamore

function cal response

deficiency of
hence consuming
High inhibt products
involve excretion
calcium
than blood regulatedof fiber,
remainder, absorption and
during 1979). unclear. 1981). on lactose,
milk
more is activation,
hormone in
1965; nutritional by
retention,
personsHigh are
Leafy-g
mg), dietary regulated compensated
urinary effect
dietary
is as al., the al., and
and (900 absorption high, is content. and
al., et offset
The transmission,
body, when
Intestinal and of
diet et andnegative Milk
1984).
enzyme are et alsosevere the Allen
fluids Hegsted acids
availábl
calcium
23.1). absorption American
status may oxalates,
(Avioli increase phosphorus amino foods.
the calcium is
highest partly Linkswiler,
calciumn
extra-celluar lactation. mechanisms, 1974;
calcium a
in (Tableincluding
status calcium which
1978; have
mineral nerve age only in
certain
is for protein
calcium al., North phytates,
effect,
al., may distributed
calcium bone Intestinal
Absorption with
of is elevated
requirements
and
contractibility, et the and
which
theprocesses,
abundant cxcretion
adaptive
progressively in
et
high-protein
(Spencer
hence
including of
readily
(Schuette
in pregnancy, affect (Margen on hypocalciuric
as
and
stored high
of transport. (hypercalciurea),
effect an such widely
D. factors and
ssessment (I0g)metabolic Urinary
of Diets have
most
is and/or protcin factors, excellen
components, sources
rcsult absorption absorption
muscleviamin rare. thismixed
also
absorption
not
thecalcium
tissues membranegrowth, decreases other status. a
low a is
1970).
As calcium
of have
diets the Other is
status.
is several via
agulation, nornal,
importance Calcium
A Calcium
body
body are Several calcium
rapid need. calcium calcium of
intakes
protein calcium
dietary calcium
marily al., effect
23.1 and takes cium
of in in of et to of the
489 of
absorption
sources
calcium, 1982:
et(Heaney
intakes
of regularly,
intakes the decreased
adults smoking,
overprogressively
by In affectedand
treatments
drug conimation
and(Anderson
diuretics linked dietary
not density
calcium
ofResults
negativehypercalcemia.
or Th intakessyndrome
persons assesSing
is used calcium remarkably
reduces protein, have hyperparathyroidism skeleton. calciumLow
under
calcium
al.,
limit
may and
these calcium between 1978).
is weight,some been bone been
studies
be
Nevertheless,promising
calcium 1984).
sources
poor loss losses
calcium, alkali can bone
axial of absorption.
from masschuractcrizcd
decreascs further
have und for of
Inadequate and have Luckey, techniques remain
index periods
Linkswiler,
bonc association method
calciumconsumedbone
fractures. bodyhyperthyroidism)
mineral
antacids), intakes Epidemiological
intake cause that milk the
appears
of
assessment
mass includingrcquires loss
concluded
and/or an and prolonged
and calcium
adult bone lifestyle,
The 1979).
calciuA bone to and adults. biochemical as controlled
bone condition
a
are
clcium
bone unlikely
of noninvasive,
calciumappendicular used
to
susceptibility
increased aluminium-containing
association 1987). (Venugopal stones
not inadequate. mineralized
and
1%. factors, the postmenopausal
result healthy indirect
nuts peak influence al.. calcium. deprivation,
with
clarifybetwecn
are adult as has kidney stores. concentrationsafter
be (Schuette
about Low al., ionized
andproducts larger such(e.g. ct
osteoporosis. are the Administration homeostatically
cannot interference
although peak osteoporosis, Nutritional Matkovi for routine an levels
ofoccur
slatus grains,be 1979). et calcium indirect, calcium
factors
diseases also
this1982). relationship Riis normally
D safeof of serum
the provide
conditions
of of to vitamin intakes
formation either concentrations
although
milkmay 1982), required on 1986:
A only
massrate
sources, non-nutglruitcocor
ional ticoids, are satisfactory
Geboers,
al.,
calciu Meats, çalcium annual may Severalmeasurements
body
the riskcertain1982). et
studiesof although
in calcium calcium following
1978; is day excessive
of
Asses menl available subsequent
and
lifeearly
durinofg age,
intakes,
goodlow,milk al., risk andmassbone averageabuse,al., phosphoruand
etSpencer

and
Allenhypertension, consistental., intakes
s isworkintakeal.,supplementation
et
(Freudenheim
of
latterDrug
intakesperthe
mass
below.
andmgto no status,
bone
an
index
of
Serum

are
they
calcium
most
Serum
because or
et 1977; (Kesteloot et Excessive
the predisposed
alcohol(Spencer
of avoid
alsobe ifHence, years Food2500 is described
excessive neasure
ass
Morecalcium (Heaney
afound Instead, calcium Content,
There constant
are
may of
an
35 at by
(e.g. al.,with U.S.to
up
should Serum
L3.1,1status
et
 490 Assessment of calcium, phosphorus, and
magnesium status
Fifty percent of the calcium in plasma is ionized and

bound to protein, primarily albumin, and 5% to 10% is

physcomplexed
active. It is this fraction that is under hormonal control. The
50% is not ionized and is physiologically inert; of this, 40% to iorelomaigi50%cnalinlgy
is
citrate, bicarbonate, and phosphate. Serum rather than plasma with
should be
used for calcium analysis; most anticoagulants function by reacting
calcium. with
If scrum calcium concentrations are outside the normal
logical rather than nutritional problems should be suspected.range,
Fot
patho-
exam-
ple, in cases of hypoparathyroidism, hypomagnesemia, and acute pancre-
atitis, serum calcium concentrations are low (hypocalcemia).
serum calcium values (hypercalcemia) occur in association with Elevated
parathyroidism, hyperthyroidism,sarcoidosis, and when large areas hyper-
ofthe
body are immobilized (e.g. after spinalcord injury and bone fracture), to
the latter, calcium from the rapidly atrophying bonc is relcased into the
cireulating body fuids.
Serum calcium concentrations in nomal healthy adults range from
8.8 to 10.6 mg/dL (2.20 to 2.64 mmol/L). Values decrease with age in
men. Females haveslightly lower concentrations (8.8 to 10.2 mg/dL:2.20
to 2.54 mmo/L) than males (9.2 to 10.6 mg/dL; 2.30 to 2.64 mmo/L),
associated with small differences in serum albumin content and the
calcium-rcducing effect of estrogens. Serum calcium decreases by 5%
to 10% up to the end of the third trimester of pregnancy, after which
concentrations rise. Scrum calcium concentrations were determined in
both the NHANES I survey (NCHS, 1979) and the Nutrition Canada
National Survey (Hcalth and Welfare Canada, 1973).
Serum calcium is used to identify vitamin D intoxication. Elevated
serun calcium levels (hypercalcemia) invariably result from excess vita
min D (Section l8.2.4). Serum calcium is usually determined by flame
atomic absorption spectrophotometry (AAS) (Zettner and Seligson, 1964).
Earlier methods included flame photometry and the calcium oxalate titra
tion procedure.

23.1.2 Serum ionized calcium concentrations

Serum ionized calcium, which makes up 50% of the calcium in plasma,
is the physiologically active form of calcium in the blood. It can be
measured using commercially available ion-speciic electrodes (Wandrup
and Kvetny, 1985). Serum ionized calcium concentrations, rather h
fotal serum calcium concentrations, relate to disturbarnces in calcium
in hypo-
metabolism. Reductions in ionized calcium concentrations occurincreased
parathyroidism and vitamin-D deicient rickets, and result in
neuromuscular iritability. Elevated ionized calcium values sugges
functional hypercalcemia, and occur in patients with hyperparathyroidism
total serum
or receiving chronic renal hemodialysis. In such conditions,
Assessment of
calcium stalus 491
normal (Ladenson
and Bowers, 19736). Serum
levels may be
ionized calciumn concentrations cannot be predicted
calcium from total serum
calcium values because only a low correlation exists between ionized
calcium and total serum calcium concentrations in healthy persons.
Ladensonand Bowers (1973a) reported a mean serum ionized calcium
concentration of 1.28 mmol/L (rang 1.18 to 1.38 mmol/L) for eighty-
apparently healthy adults (nineteen to ifty years). This mean value
six
coesponds closelytothat obtained in some earlier studies (Oreskes et al.,.
Piechocki, 1971). In general, adult males have a higher
Li andjonized
1968;
mean serum calcium concentration than females. Discrepancies
reference values for serum ionized calcium in adults, some of
exist forthe
attributed to difficulties in collecting and handling serum
which may be
anaerobically and to differences in the electrode systems used
samples Kvetny, 1985).
(Wandrup and
Several confounding tactors affect the measurement of serum ionized
oalcium concentrations. These include high levels of magnesium and
sodium, the presence of trypsin, triethanolamine, and heparin, and
changes in pH of the sample (Ladenson and Bowers, 1973a). The
confounding effects of magnesium and sodium can be eliminated by
using calcium standards containing sodium and magnesium chloride in
the same concentrations as those expected in the samples. Trypsin,
used.
triethanolamine, and heparin bind calcium and should be not be
The effect of changes in pH of the blood during collection and storage
collecting
on serum ionized calcium concentrations can be minimized by
and handling the serum samples anaerobically, and by adjusting the pH
to 7.4 with CO2 gas before the measurement (Schwartz, 1976). Fasting
blood samples should be used to eliminate the effect of a recent meal on
serum ionized calcium concentrations.
Wandrup and Kvetny (1985) recommend using whole-blood samples
for ionized calcium measurements. Samples should be collected, and
then stored anaerobically at 0°Cto 4°Cprior to the measurement.

23.1.3 Radiogrammetry
the cortex of
aulOgrammetry measures the thickness and the diameter of
ne metacarpals or radius on standard anterio-posterior roentgenograms
(Arays) of the hand, The X-rays can be taken in the field with portable
measurements,
qupment. A dial caliper or a digitizer is used to take the
(Kimmel, 1984).
CWnich cortical bone volume can be calculated in cortical bone
Mateasurements can be used to monitor changes
o E . No infomation on trabecular bone is obtained
using this method
can be
these measurements
(Cummi ngs et al., 1985). Hence, although
performed precisely, they do not accurately reflect the total
amount of
skeleton, as
bone present, and correlations with the total mass of the
 and
492 Assessnent of calcium, phosphorus, magnesium status
determined by ncutron activation, are poor. This method will not reliably
20% in cross-sectional studies,
detect bone loss of less than

23.1.4 Single photon absorptiometry method ae

the most practical noninvasive
Single photon absorptiomctry iscontent al.. 109
measuring total bone mineral of the limbs (Wahner et
that bone mineral content
The method is based on the assumption energy transmitted by
inverselyy proportional to the amount of photon measurement hy
bone under study. The site most frequently selected for
single photon absorptiomeiry is the lower radius, at approximately one.
third of the distance from the styloid process to the olecranon. Bone
mineral content of this site correlates well with that of the hin
content in healthy adulte
with the total skeletal mineral and calcium errors (10%%
(Mazess, 1971), with errors ranging from 5% t0 10%o. Larger
(Cohn et al., 1974a).
io 15%) may arise when osteopenic subjects are usedmeasurements on the
Single photon absorptiometry is not suitable for of sof
axial skeleton because the technique requires a uniform thickness
of the lower
issue surrounding the bone. The bone mineral content
"adius correlates only weakly with the amount of trabecular bone in the
spine (Mazess, 1983). Hence, this method cannot be used to predict bone
nineral content or density of the vertebrae, especialy in patients with
netabolic bone disease (Mazess et al., 1984a).
For single photon absorptiometry, the lower radius is exposed to aa
from
mall amount of radiation (0.02 to 0.05 mGy; 2 to 5 mrad) quantity
nono-energetic photon source-usually 2| or 241 Am. The
of bone mineral positioned in the beam path is inversely related to
he amount of transmitted radiation, measured by a scintillation counter
Boyd et al., 1974). To standardize the measurements armong individuals
vith different bone sizes, bone mincral content can be expressed as bone
nineral per square centimeter of bonc (i.e. as g/cm²) (Harper et al., 1984).
\lternatively, an index based on the ratio of bone mineral content to the
vidth of the radius can be used (Mazess, 1971). The technique is fast,
aking approximately five minutes. Precision and accuracy of the method
ange from 3% to 5%, and 2% to 4%, respectively (Mazess, 1971);
alues correlate well with those determined by conventional techniques.
he method can be used to measure rate of bone loss in prospecuve
ongitudinal studies, if positioning errors are minimized.
Diagnosis of osteoporosis from measurements of total bone mineral
ontent of the limbs of the appendicular skeleton by single photon
bsorptiometry is usually based on values which fall below the nomalSuch
ange of bone mass of healthy adults (Horsman et al., 1981).
ference data have becn derived from several studies in the United States
nthe bone mineral content of the midshaft and distal end of the radius
Mazess and Cameron, 1974; Hui et al.. 1985). In the future, 1t
 fcalcium status 493
Assessmenlof

assess fracture risk using absolute levels of bone mass

possible to Gerhart, 1985).
Hayes and
(Parfitt,1984;
be

photon absorptiometry
23.1.5 DDualabsorptiometry can be used to determine total bone mineral
photon using the lumbar vertebrae sites, as well as
Dual the axial skeleton,
contentofmineral content of the proximal femur. Thc method uses a ra-
the bone sourcethat emits twO gamma rays, usually 133Gd with gamma
dioisotope
44 and 100
KeV, enabling bone density to be assessed indepen-
rays at
soft-tissue thickness and composition. The technique takes
dently of with a radiation exposure to local tissues
approximatelyfifteen minutes
0.15 mGy (5 to 15S mrad). Precision and accuracy of the method
of 0.05to 3% and 4% to 6%, respeciively (Kimmel, 1984). The lumbar
are 2% to the sites generally sclected. The stemum inter-in
(L2 to LA) are
vertebrae measurement if thoracic vertebrae are used. Calcification
feres with the
oSteoarthritis of the spine, and vertebral compression fractures
the aorta, Diagnosis of
scanning area, may all confound the measurement.
the by dual photon absorptiometry is gen-
osteoporosis from measurements less than the
on levels of bone mass which are at least 20%
erally based 1984b).
comparable, healthy males or females (Mazess et al., from
mean for total skeleton is best predicted
mineral content of the
The bone content of both the appendicular
and
measurements of the bone mineral
axial skeleton.
23.1.6 Computerized tomography
tomography can be used
(CT) (Section 14.7.4) skeleton,
Although computerized appendicular and axial the
both the
to measure bone mass of studies. The equipment is not portable
not feasible for survey
method is
involves a high radiation dose (2.0 to 2.5 mGy; 20O
and the method Furthermore, precision is lower than
mrad) (Kimmel, 1984).
to 250 (3% to 5%) and accuracy is poor
that for dual-photon absorptiometry
changes markedly affect results because of
(12%); even small position 1983).
confounding effect of the bone marrow fat content (Mazess,
the
and may result in misleadingly low CT
latter increases in the elderly
Ihe
neasurements. Computerized tomography can be used to measure only
some forms of osteoporosis are
trabecular bone, an advantage because
predominantly trabecular in character.

23.1.7 Neutron activation

vivo method assesses total body calcium content. As 99%o of total
nis tn calcium is arelatively constant
calcium is in the skeleton, and asweight, measurement of total body
n(38% to 39%)of bone mineral
body bone mineral content, except
i n provides an estimate of total of calcium occur. The method is
o wnere extra-osseous deposits
 Assessmnent of calcium, phosphorus, and magnesium status
494

based on the conversion of a proportion of 48Ca in the body to 49 Ca by

neutron ffux. The patient &
exposing the body of the patient to a lowwhere the gamma rays emitt
then transferred to a whole-body counter detectors. The gamma ra
by the 49Ca are counted by sodium iodide calcium. Results of thi
count is proportional to the mass of total body of the loWer
technique correlate well with single photon absorptiometry this method
radius (Mazess, 1983). The total radiation exposure using depending on the
varies from 2.5 mSv to 25 mSv (0.25 rem to 2.5 rem)
photon absorptiometry
neutron source, arange considerably higher thanmethod.
of the The preferred
and limiting the general applicability determinations of
neutron source is 238PuBe. The precision of repeated period
total body calcium by neutron activation over a.four- to five-year
in healthy adults is estimated as 2.5%, suggestingal., that the method is
suitable for studying longitudinal changes (Cohn etbone 1974b).
index (CaBI) in
Harrison et al. (1979) have developed a calcium This index
which total body calcium content is normalized for body size.
1.0±0.12) and
may be used to distinguish between normal (with CaBI
in patients who
oSteoporotic (0.69 ±0.10) subjects. Mild osteoporosis detected.
have not yet experienced any vertebral fractures can be

23.2 Assessment of phosphorus status

Phosphorus is the second most abundant mineral in the body. About
calcium
85% of phosphorus in the adult body is present in the bones as
phosphate [Cas(P04)2] and hydroxyapatite (Cajo(PO4)6(OH)2]. The
remainder is in cells and extracellular fluids as inorganic phosphate and
in combination with proteins, lipids, carbohydrates, and other compounds
(Table 23.1). Phosphorus is an essential factor in all the energy-producing
reactions of the cells.
Phosphorus is widely distributed in animal and plant foods. Protein
rich foods, such as meat, poultry, fish, eggs, milk, and milk products, are
American diet. Whole
major sOurces of phosphorus in a mixed North
graíncereals, legumes, and nuts are also good sources. Dietary dehciency
exceed
of phosphorus is rare because phosphorous intakes generally and
requirements. Moreover, in the absence of disease, parathyroid
amount of
renal mechanisms function to conserve body phosphorus. The
dietary phosphorus absorbed depends on both the dietary intake and ue
mixed diet,
food source. In healthy adults consuming a North American
absorbed (Moon et al., 1974);
about 60% to 70% of dietary phosphorus is
r
intakesacid
maximal absorption (up to 90%) is achieved when phosphorus phytic
very low. Some sources of dietary phosphorus, for example are not
(inositol hexaphosphate) found in cereals, legumes, and nuts,
secrete a
absorbed in humans because the intestinal mucosa does not Although
phytase enzyme, essential for the hydrolysis of phytic acid. in certain
vitamin D status is known to influence phosphorus absorption