Serum protein concentrations and bone mineral

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content in aging normal men13
Eric S Orwoll, MD; Ronald M Weigel, PhD; Shelia K Oviati;
Diane E Meier, MD; and Michael R McClung, MD

ABSTRACT Low serum protein levels and low dietary protein intakes possibly influence
bone metabolism. To evaluate the relationships among serum protein concentrations, protein
intakes, and bone mineral content (BMC), we have examined two populations of normal men.
BMC was measured at two radial sites and a vertebral site. Aging was associated with a fall in
BMC at all sites. Serum albumin levels also fell with age and were related to BMC. Albumin
concentrations were associated with BMC when other variables (calcium and protein intake,
vitamin D levels, parathyroid hormone, and urinary calcium) also were considered. Thus, al-
terations in protein metabolism may affect BMC and may play a role in the genesis of senile
osteopenia. Am J Clin Nuir l987;46:614-21.

KEY WORDS Osteopenia, bone mineral content, aging, protein nutrition, calcium nutrition,
albumin

Introduction Subjects and methods

Subjects
The universal decline in bone mass that occurs with
aging apparently results from the interaction of many Study one. To evaluate the rate of bone mineral content loss
variables, including genetic, metabolic, physical, and nu- in normal men with aging we recruited 62 normal subjects from
tnitional factors. Dietary protein influences mineral me- the Portland community. Their ages were evenly distributed be-
tabolism because protein supplementation results in cal- tween 30 and 90 y (mean 56 ± 16 (SD)), and none had clinical
evidence of osteopenia or of conditions associated with the de-
ciuresis and worsening calcium balance (1, 2). Concern
velopment ofosteopenia. To better define the rate of age-related
has arisen that the relatively high-protein intake charac-
bone loss in normal men, proximal and distal radial bone mineral
teristic ofWestern societies may contribute to age-related contents were measured by single photon absorptiometry, and
bone loss. In fact, the practical risk to skeletal health posed vertebral bone mineral content was measured by quantitative
by a high-protein diet, if any, is unclear. computed tomography (Cl’). The specifics ofthis cross-sectional
Although less well recognized, protein undernutrition study were reported previously (6). A second purpose of this
also has been associated with osteopenia. Population evaluation was to develop a model of the causation of the bone
studies (3) suggested that human protein-calorie malnu- mineral loss that occurs with aging in this population (7). As a
trition is related to osteopenia. In addition, recent studies result of the observations concerning the possible interactions
indicated that nutritional alterations in protein metabo- of serum albumin and bone mineral content noted above, we
lism can be associated with metabolic bone disease. For
instance, Parfitt et al noted that the degree of osteopenia
in patients after intestinal bypass operations was most From the Medical and Research Services, Portland VA Medical
closely related to low serum protein levels (4). Similarly, Center, Department of Medicine, Oregon Health Sciences University,
in a study of asymptomatic subjects who previously un- Portland, OR
2 Supported by the National Dairy Council, the Veterans Adminis-
demwent partial gastrectomy we found osteopenia in as-
tration Merit Review Funds, the Medical Research Foundation of Oregon,
sociation with lowered serum albumin concentrations (5).
the Tartar Trust, and grant RR 00334 for the General ainical Research
To further evaluate the possible influence of serum al- Center, NIH.
bumin on bone mineral content and how it is related to 3 Address reprint requests to Eric Orwoll, MD, Portland VA Medical
a variety of other variables postulated to affect bone me- Center (1 1 1), Portland, OR 97201.
tabolism, we studied two independent populations of Received September 1 7, 1986.
normal men. Accepted for publication January 13, 1987.

614 Am J C/in Nuir l987;46:6l4-2l. Printed in USA. © 1987 American Society for Clinical Nutrition
 SERUM ALBUMIN AND BONE MINERAL CONTENT 615

evaluated the relationship between those two variables in this becular bone with little intravertebral heterogeneity and because
population. they usually are spared the degenerative changes common at
Study two. We reevaluated those relationships in a second, the L4-L5 level. The precision (coefficient of variation) of the
independent group of subjects. Ninety-two normal men were vertebral CT technique was measured by 12 repeat scans of Li
recruited from the Portland community. Their ages ranged from in two men and was 4.5%. Vertebral bone mineral contents in
30 to 86 y (mean 56 ± 14). All were ambulatory and were living study 2 were measured using similar dual energy techniques (80
in their own homes and none had clinical or biochemical cvi- and 140 kvp).

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dence of bone disease. Volunteers with a history of cigarette Radial photon absorptiometry (RPA) was performed at the
smoking, excessive alcohol use (> 5 drinks/wk), vertebral or junction ofthe distal and middle thirds of the radius (proximal
nontraumatic fracture, recent immobilization, or endocrine, RPA) and at the distal radius 2 cm proximal to the ulnar styloid
renal, hepatic, or gastrointestinal disorders known to produce (distal RPA) by the 125! photon absomptiometnic technique of
abnormalities in bone or calcium metabolism were excluded Norland-Cameron using a digital bone densitometer(Model 278-
from participation. Subjects took no medications nor substances C, Norland Corporation, Ft Atkinson, WI). The precision (coef-
known to affect bone mineral content, including corticosteroids, ficient ofvariation) ofthis method was 1.8% (proximal site) and
diuretics, sex steroids, on fluoride. All subjects had normal he- 2.0% (distal site) (n = 10).
moglobin, calcium, phosphorus, alkaline phosphatase, creati-
nine, lactic dehydrogenase, glutamic oxalic transaminase, and Statistical methods
albumin concentrations and a normal urinalysis. Dietary intakes The relationships among the numerous factors implicated in
of protein and calcium were estimated by a trained research affecting bone mineral content were examined using a multiple-
nutritionist using a standardized assessment technique based on regression statistical model. In addition to serum albumin, met-
7-d dietary recall. This was a cross-sectional study, each subject abolic variables hypothesized to affect bone mineral content were
being examined only once. The protocols were approved by the included in the model (ie, 25(OH)D, PTH, etc). The variables
Committees on Human Research at both institutions involved. could be grouped into four categories, representing four levels
of causal priority, as indicated in Table 1. This model suggests
Laboratory techniques
that 1) metabolic factors have the most proximate effects on
Blood and spot urine samples in both study groups were ob- bone mineral content, 2) dietary calcium and protein affect met-
tamed for biochemical determinations after an overnight fast abolic factors directly and have effects on bone mineral content
with the subjects on their usual diets. Serum 25-hydroxyvitamin indirectly via more proximate effects on metabolic factors, and
D [25-(OH)D] concentrations were measured by the method of 3) the effects of age on bone mineral content are accomplished
Belsey et al (8) (normal range for men 10-50 ng/mL, interassay via intervening variables at the level of dietary and metabolic
variation 8%). Serum 1,25-dihydroxyvitamin D [l,25-(OH)2D] factors and via additional factors not represented here.
and 24,25-dihydroxyvitamin D [24,25-(OH)2D] concentrations The interrelationships among the variables at the different
were measured in the laboratory of Dr Anthony Norman (Riv- causal levels were studied as follows. For each bone mineral
erside, CA) (9, 10). The lower limits of detection in the 1,2S- measure the causally prior variables were entered into the mul-
(OH)2D and 24,25-(OH)2D assays were 25 and 5-10 pg, respec- tiple regression model in the following order: 1) All independent
tively. Normal serum concentrations in Southern California variables were entered into the model. Variables not making a
subjects were 3.7 ± 1 .2 ng/mL and 42 ± 1 1 pg/mL for 24,25- significant independent contribution (p < 0.05) in accounting
(OH)2D and 1,25-(OH)2D, respectively. Samples were collected for variance in bone mineral content were eliminated by the
in Portland and coded before shipment to Riverside. stepwise method. This is the full model, including age as well
The parathyroid hormone (PTH) measurements in study 1 as metabolic and dietary factors as predictors of BMC. 2) The
were performed in a single batch using an antiserum with pre- dietary and metabolic variables were entered into the model (ie,
dominant midregion specificity as previously reported (1 1), and only age was excluded) with subsequent stepwise removal of
by similar methods in study 2 (PTH midmolecule immunoassay, nonsignificant variables. 3) Only the metabolic variables were
Endocrine Metabolic Center, Oakland CA). Urinary cAMP
concentrations were measured by the method of Gilman (12)
and were expressed as a function of the glomerular filtration
rate (nM cAMP/l00 mL OF). Serum total Ca, P, creatinine, TABLE 1
alkaline phosphatase, and albumin concentrations were mea- Causal levels of variables in stepwise regression model*
sured by autoanalyzer (Technicon Instruments Corp, Tarrytown,
Demographic Dietary Metabolic Bone
NY) techniques. The coefficients of variation for these deter- variables variables variables measurest
minations were 2.7, 3.0, 3.4, 8.7, and 2.7%, respectively. Urine
Ca concentrations were measured by atomic absorption spec- Age Protein Serum albumin Proximal radial
trophotometry (Varion Instruments, Spningvale, Australia) and BMC
urine creatinine concentrations were measured by a modified Calcium 25-hydroxyvitamin D Distal radial
Jaffe reaction (13). BMC
1,25-hydroxyvitamin D Vertebral BMC
Measurement ofbone mineral content 24,25-dihydroxyvitamin D
Parathyroid hormone
In study 1 , vertebral mineral content was measured using a
Cyclic AMP
rotary fan-beam computed tomographic scanner at 80 mA, 120
Calcium creatinine
kvp (CT/T 8800, General Electric, Milwaukee, WI). Mineral
clearance
content was determined in the midplane offour vertebrae, Tl2-
L3, in a single 1-cm thick slice obtained at each level as previously * For each variable, causal variables are to the left and consequences
reported by Oenant and Cann (14). These vertebrae were chosen are to the right.
because they provide a large area for measurement of pure tra- t BMC = bone mineral content.
616 ORWOLL ET AL

TABLE 2 2, and with vertebral bone mineral content in both groups

Correlations of bone mineral content (BMC) with prior variables* (Table 2, Fig 3). Dietary protein also is positively corre-
lated with vertebral bone mineral content in both groups
Prox Dial Veil
Variable Group RPA RPA BMC
and with proximal radial bone mineral content in study
2; 24,25-(OH)D concentrations were positively correlated
Age I -0.27t -0.35t -0.71f
with vertebral bone mineral content in both study groups,
2 -0.53 -0.47 -0.77
and 25-OHD levels were positively correlated with ver-

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Dietary calcium 1 0. 19 0. 15 0.00
2 0.2 lt 0.07 0.23t tebral bone mineral content in study 1. No other variables
Dietary protein 1 0.20 0.03 0.27t showed strong correlations with measures ofbone mineral
2 0.22t 0.15 0.30t content.
Serum albumin 1 0. 10 0. 19 0.60t The results ofthe multiple regression analyses are pre-
2 0.22t 0.28f 0.46f sented in Table 4. The partial correlations reported in-
25-hydroxyvitamin D I -0.01 0.24 0.46 dicate the association ofeach variable with the bone mm-
2 -0.06 -0.09 0.03 cml content measure specified, independent of the other
1,25-dihydroxyvitamin D 1 -0. 12 0.08 0.11 variables included in the designated model (15). The as-
2 0.00 0.19 0.09
sociation of increasing age with decreasing bone mineral
24,25-dihydroxyvitamin D 1 0.23 0.2 1 0.49f
content is the strongest independent pattern in the data;
2 0.05 0.03 0.24t
Parathyroid hormone 1 -0.06 -0.28t -0.29t there was a significant (p < 0.05) negative part correlation
2 -0.05 -0.09 -0.06 ofage with all three bone mineral measures in both study
Cyclic AMP 1 -0. 13 -0.27t -0.23 groups. The only other associations with bone mineral
2 -0.09 -0.03 -0.13 content in the full model (ie, including age) were weak
Calcium creatinine 1 -0.30t -0.10 -0.19 associations (0.05 < p < 0.01) of vitamin D measures
clearance 2 -0.07 -0.2lt -0.1S with cortical BMC. However, in the regression model not
* Prox RPA = proximal radial BMC, Dist RPA = distal radial BMC, including age (ie, the metabolic + diet model), the only
Veil BMC = vertebral BMC. variable showing a consistent significant association with
tp<0.05. BMC was serum albumin, which was positively correlated
fp<0.Ol. with all three BMC measures in study 2 and with vertebral
bone mineral content in study 1 . The independent asso-
ciation of albumin with bone mineral content, as mea-
entered with subsequent stepwise elimination. This method per- sured by the partial correlation coefficient, was essentially
mitted the assessment of the proximate factors affecting bone identical whether or not the dietary factors were taken
mineral content and the ability ofthe proximate metabolic fac- into account.
tors to account for correlations observed between bone mineral Fig 4 presents a Ballantine diagram (15) revealing the
content and the more distant variables, diet and age. contributions to variance in vertebral bone mineral con-
tent accounted for by the two variables with the strongest
Results independent associations in the multiple regression anal-
yses: age and serum albumin. Section a represents the
The simple correlations (Pearson’s r) ofthe independent
variables with bone mineral content are shown in Table
2. The strongest correlations observed are those indicating 0
that increasing age is associated with decreasing bone 210
mineral content at all three measurement sites (vertebral, 0
0
0
190
proximal, and distal radial, p < 0.01 in all cases). The 0

effects of aging on bone mineral content were most dra- r

C.)
matic at the vertebral site in both populations (Fig 1) (8). 150 00

0
Table 3 shows the simple correlations (Pearson’s r)

i
130 0 0

among the independent variables in the regression model, 00 B

i;:
which aids in the interpretation of the manner in which 0

the variance in bone mineral content accounted for by 0

B
age can be explained via the mole ofintervening variables. 0
0
70
The variable in the model most highly correlated (nega- 0

50
tively) with age is serum albumin (p < 0.01 in both study
groups) (Fig 2). At the level of dietary factors, protein 30
0
intake is positively correlated with serum albumin in both 10
20 40 60
study groups. Dietary protein and Ca intakes were highly
positively correlated, but neither dietary factor was #{163}GE(YRS.)

strongly correlated with age. FIG 1. The relationship ofvertebral bone mineral content (BMC) to
Serum albumin levels were positively correlated with age-study group 2. Dotted lines show the 95% confidence intervals for
proximal and distal radial bone mineral contents in study the regression.
 SERUM ALBUMIN AND BONE MINERAL CONTENT 617

TABLE 3
Correlations among independent variables in regression model

Variable Study DIETCA DIETPRO Albumin 25-(OH)D l,25(OH)D 24,25(OH)D PTH CAMP CACRCL

Age 1 -0.08 -0.3 lt -0.65 -0.48t -0.06 -0.381 0.23 0.3t 0.16
2 -0. 18 -0.26 -0.48t 0.00 -0. 17 -0.22t 0. 13 0.08 0.11
DIETCA 1 0.5Sf 0.19 0.03 0.1 1 0.06 0.13 0.1 1 -0.09

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2 0.76f 0. 17 0.22t 0. 15 -0.02 -0. 15 0.07 0.43t
DIETPRO 1 0.3Sf 0.16 0.25 0.13 0.10 0.01 -0.05
2 0.21t -0.03 0. 16 0.01 -0.20 0.06 0.23t
Albumin 1 0.44f 0.27t 0.43t -0. 17 -0.07 -0.24
2 0.03 0. 13 0.24t -0. 1 1 0.01 -0.07
25-(OH)D 1 0.26t 0.68f -0.38 -0.23 0.10
2 0.02 0.59f 0.01 -0.05 0.06
1,25-(OH)D 1 0.09 -0.09 0.02 0.01
2 0.07 0.04 -0.08 0.14
24,25-(OH)D 1 -0.24 -0.29f -0.16
2 0.01 -0.15 -0.09
PTH 1 0.3Sf 0.02
2 -0.03 -0.15
CAMP 1 0.18
2 0.3l
S DIETCA = dietary Ca intake, DIETPRO = dietary protein intake, Albumin = serum albumin concentration, PTH = parathyroid hormone
concentration, CAMP = cyclic AMP, and CACRCL = urinary Ca-creatinine clearance ratio.
tp<0.05.
jp<0.0l.

proportion of variance in vertebral bone mineral content content were considered simultaneously to assess their
accounted for by age independent of serum albumin independent associations with bone mineral content, age
(study group 1; 21%; study group 2; 40%) and section b was the only variable showing a consistent and significant
represents the proportion of variance in vertebral bone correlation. However, when age was dropped from the
mineral content accounted for serum albumin indepen- model, serum albumin became the only variable asso-
dent ofage (study group 1: 3%; study group 2: 1%). Section ciated with bone mineral content. The high negative cor-
c represents the proportion of variance in vertebral bone relation ofage with serum albumin thus suggests that one
mineral content accounted for by age and serum albumin ofthe factors responsible for the decreasing bone mineral
cojointly (study group 1: 32%; study group 2: 19%). With content characteristic ofincreasing age is serum albumin.
the designation of age as a factor causally prior to serum Ideally, a model ofcausal priority would have proximate
albumin, section c represents the indirect effect ofage on factors account completely for any associations observed
vertebral bone mineral content via the intervening variable between variables, as would be indicated in this study by
serum albumin. It is apparent that, although the effects significant part correlations of serum albumin with bone
of albumin on vertebral bone mineral content indepen- mineral content when age is included in the regression
dent of age are small, a large proportion (20-30%) of the model (20). However, the associations of BMC with age
variance in vertebral bone mineral content accounted for were greater than those of the more causally proximate
by age is in conjunction with serum albumin. serum albumin. There are several interpretations for this
result. First, age is measured with higher reliability than
Discussion serum albumin, ie, the measurement of serum albumin
levels has an associated error due to imperfections (albeit
On the basis of previous assessments at radial and small) in assay techniques or serum albumin levels may
metacarpal sites (16, 17) the loss of BMC with age has fluctuate within individuals so that precise determinations
been considered to be minor in normal men. This study, of the average levels are difficult. In such a case the pop-
which extends our previous experience (6), provides fur- ulation correlation of mean serum albumin with BMC
them evidence for a progressive decline in BMC with age may in reality be greater than that for age, but due to
in normal men and indicates that loss of vertebral BMC greater unreliability the appreciated correlation is less. A
is substantial. Cann and Genant noted a very similar de- second and more appealing explanation is that the effects
dine in vertebral BMC in men with age (18). This infom- ofage on BMC operate via a number ofintervening van-
mation coupled with an obvious increase in fracture rates ables with albumin being one ofthe major ones, but that
in aging men (19) clearly indicates a need to better un- additional variables not measured here account for a sig-
derstand the process of senile osteopenia in men. nificant additional proportion of the remaining variance
When the factors potentially affecting bone mineral in BMC. Both ofthese interpretations support the mole of
618 ORWOLL ET AL
5
proteins on remodeling, albumin could contribute mdi-
4.9
mectly to bone metabolism, for instance, by acting to fa-
4.8 0
cilitate the uptake of minerals by virtue of albumin-cal-
4.7 0 cium or albumin-phosphorus binding. On the other hand,
-i
Q 4.6 0 the relationship between serum albumin levels and BMC
4.5 0 may be merely a reflection of broader changes in protein
metabolism, perhaps involving changes in hepatic func-

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4.4 0 0 0

4.3 0 00
tion or protein nutrition which in turn affect bone me-
tabolism.
4.2 0 00 0

The decline in serum albumin levels with age in both

4.1 00

C,) populations studied here was previously described in large

4 0 0 00
cross-sectional studies (23). Alterations in albumin me-
3.9 0
tabolism have been associated with aging (24) but in fact
3.8 the mechanisms responsible for the decline in albumin
3.7 levels with age is unknown. The relationship between
20 40 60 80
100 serum albumin concentrations and dietary protein intake,
AGE (YRS.)
particularly in subjects with moderate intakes as in the
populations studied here, is also unclear. In previous
5.2

5.1 0

5 0

4.9 00 0 220
. 4.8
0000 00
0 200
0 0 0 0
4.7
4.6 180

4.5 0 0 00
160
4.4 00 0 0 0
C.)
140
: 0 0 000
C.)
4.2 0 0 000 0
120
i;i 4.1 0 0 0 0
100
4 0

3.9 80
3.8 0
60
3.7 , , , ‘ I I

20 40 80 80 100
40
AGE (YRS.)
20
FIG 2. The relationship between aging and serum albumin concen- 4.1 4.3 4.5

trations in study group 1 (2A) and study group 2 (2B). The dotted lines SERUU ALBUMIN (GM/DL)
represent the 95% confidence intervals for the regression.
0

210#{149}

190
serum albumin as a causally intervening variable ac- 0 a
B 5
counting for some of the effects of age on BMC. A third #{149}‘ai
170
0
a
U
explanation is that albumin has no meal effect on BMC 0 150
0 0
B a
but is correlated with BMC only because it is correlated a
U 130 0 0
with age or other variables not examined. This is a rca- B 0
sonable possibility but one that can not be evaluated fur- 1:

them with currently available data and thus requires more a 0

0 0
specific testing. 0 0 0
70 0
These correlational studies therefore suggest that 0
0 B
50 0
changes in protein metabolism have a pathophysiologic
relationship to the age-related decline in bone mass noted 30
0
in the two populations studied here. Although the mech-
anisms that might mediate this putative influence are un- 3.7 3.9 4.1 4.3 4.5 4.7 4.9 5.1

clear, several possibilities exist. Triffett et al (21, 22) dem- SERUM ALBUMIN (GU/DL)

onstrated an interaction of serum proteins (albumin and FIG 3. The relationships between serum albumin concentrations and
glycoproteins) with mineralized tissues, an interaction that vertebral bone mineral content in study group 1 (3A) and study group
may reflect a mole for albumin in bone remodeling. In 2 (3B). The dotted lines represent the 95% confidence intervals for the
addition to the possibility of a direct influence of serum regression.
 SERUM ALBUMIN AND BONE MINERAL CONTENT 619

TABLE 4
Part correlations of bone mineral content (BMC) with prior variables

Variable Model Group Prox RPA Dist RPA Veil BMC

Albumin Metabolic 1 NS NS 0.43t

2 0.23t 0.28t 0.45t

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Metabolic + diet 1 NS NS 0.43t
2 0.22 0.28 0.38t
Full model 1 NS NS NS
2 NS NS NS
Calcium-creatinine clearance ratio Metabolic 1 -0.30 NS NS
2 NS NS NS
Metabolic + diet 1 -0.30 NS NS
2 NS NS -0.2lf
Full model 1 NS NS NS
2 NS NS NS
Parathyroid hormone Metabolic 1 NS -0.27t NS
2 NS NS NS
Metabolic + diet 1 NS -0.27 NS
2 NS NS NS
Full model 1 NS NS NS
2 NS NS NS
25-hydroxy D Metabolic 1 NS NS NS
2 NS NS NS
Metabolic + diet 1 NS NS NS
2 NS NS NS
Full model 1 -0.3l NS NS
2 NS NS NS
24,25-dihydroxy D Metabolic 1 NS NS 0.26t
2 NS NS NS
Metabolic + diet 1 NS NS 0.26t
2 NS NS NS
Full model 1 0.30t NS NS
2 NS NS NS
Dietary calcium Metabolic + diet I NS NS NS
2 NS NS 0.23f
Full model 1 NS NS NS
2 NS NS NS
Age Full model 1 -0.30 -0.35t -0.56t
2 -0.53t -0.47t -O.77t
4 Prox RPA = proximal radial BMC, Dist RPA = distal radial BMC, Veil BMC = vertebral BMC.
tp < 0.01.
p<0.05.

studies, protein intake was noted to decline with aging tially important. For instance, the well-documented de-
(25) and there is some evidence to suggest that the need creases in the rates of protein synthesis that occur in ad-
for dietary protein does not decrease proportionately (26, aptation to low protein intakes (29) and that may occur
27) resulting in a relative protein deficiency. Others noted with aging could affect the rate of new bone formation.
that when protein intake is expressed in relation to total Much concern was expressed recently regarding the
calories (the protein-energy ratio) there is an association possible role of excessive protein intakes in age-related
with serum albumin concentrations in elderly people (28). bone loss. In young men (1, 2) as well as in postmeno-
In these studies, the association ofage with serum albumin pausal women (30), increases in protein intake have a
existed somewhat independently ofdietary protein intake negative effect on Ca balance, primarily by increasing
in that serum albumin was correlated with dietary protein renal Ca clearance without a concomitant increase in gas-
but the correlation ofage with dietary protein was weaker. trointestinal Ca absorption. Nevertheless, the adverse ef-
In essence, theme was a decrease in serum albumin with fects of protein on Ca metabolism are considerably
increasing age that existed independently ofan associated blunted when protein is ingested as part ofa mixed intake
decrease in protein intake. The nature ofthese interactions rather than as a pure supplement (30, 31). In addition,
between protein nutrition, protein metabolism, bone me- the progressive worsening of Ca balance associated with
tabolism, and aging are apparently complex but poten- N intakes above the recommended dietary allowance
620 ORWOLL ET AL

5. Klein KB, Orwoll ES, Lieberman DA, Meier DE, McClung MR.
Parfitt AM. Metabolic bonedisease in asymptomatic men after partial
gastrectomy with Biliroth II anastamosis. Gastroenterology (in press).
6. Meier DE, Orwoll ES, Jones M. Marked disparity between trabecular
and cortical bone loss in healthy men with age: measurement by
vertebral computed tomography and radial photon absorptiometry.
Ann Intern Med I984;lOl:605-l 1.

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7. Orwoll ES, Meier DE. Alterations in calcium, vitamin D, and para-
thyroid hormone physiology in normal men with aging: relationship
to the development of senile osteopenia. J Gin Endocrinol Metab
(in press).
8. Belsey R, DeLuca HF, Potts JT Jr. Competitive binding assay for
vitamin D and 25-OH vitamin D. J Clin Endocrinol Metab 197 I;33:
ALBUMIN 554-7.
9. Norman AW, Bishop JE, Jongen M. Measurement of vitamin D
metabolites. In: Cohn DV, Potts JT, Fjuita T, cdi. Proceedings of
AGE the workshop on the action ofcalcium regulating hormones in cells.
Amsterdam: Exerpta Medica, 1984:7-10.
FIG 4. A Ballentine diagram (15) illustratingthe interactions between 10. Bishop JE, Norman AW, Coburn JW, Roberts PA, Henry HL.
the variables vertebral bone mineral content (BMC), serum albumin, Studies on the metabolism of cholecalciferol XVI. Determination
and age in study group 2. of the concentration of 25-hydroxyvitamin D, 24,25-dihydroxyvi-
tamin D and l,25-dihydroxyvitamin D in a single two milliliter
plasma sample. J Mm Elect Metab 1980;3: 181-9.
11. Orwoll ES, Kopel A, Opsahl Z, Roberts L, Endres D, McClung MR.
(RDA) does not appear to extend to intakes less than that. Hypochlorite radioiodination ofparathyroid peptides (hPTH 1-34,
[Tyr 43]hPTH 44-68). J Lab Clin Med 1985;I05:247-53.
Chu et al demonstrated that, on average, Ca balance in
12. Oilman AG. A protein binding assay for adenosine 3’:5’-cycic
young individuals was unaffected by protein intakes up
monophosphate. Proc Natl Acad Sci USA 1970;67:305-12.
to 12 N/d and only began to suffer at higher intakes (32). 13. Tietz N. Fundamentals of clinical chemistry. Philadelphia: WB
In fact, in the majority of their subjects Ca balance was Saunders, 1970.
improved by increasing N intake from 0.9 to 12 g/d, mis- 14. Oenant HK, Cann CE. Vertebral mineral determination using
ing the possibility that low protein consumption may ad- quantitative computer tomography. In: DeLuca MF, Frost HM, Jee
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