Full text of DOI:10.1359/jbmr.2000.15.12.2504

JOURNAL OF BONE AND MINERAL RESEARCH
Volume 15, Number 12, 2000
© 2000 American Society for Bone and Mineral Research
Effect of Dietary Protein on Bone Loss in Elderly Men and
Women: The Framingham Osteoporosis Study*
MARIAN T. HANNAN,1,2 KATHERINE L. TUCKER,3 BESS DAWSON-HUGHES,3
L. ADRIENNE CUPPLES,2 DAVID T. FELSON,2,4 and DOUGLAS P. KIEL1
ABSTRACT
Few studies have evaluated protein intake and bone loss in elders. Excess protein may be associated with
negative calcium balance, whereas low protein intake has been associated with fracture. We examined the
relation between baseline dietary protein and subsequent 4-year change in bone mineral density (BMD) for
391 women and 224 men from the population-based Framingham Osteoporosis Study. BMD (g/cm2) was
assessed in 1988–1989 and in 1992–1993 at the femur, spine, and radius. Usual dietary protein intake was
determined using a semiquantitative food frequency questionnaire (FFQ) and expressed as percent of energy
from protein intake. BMD loss over 4 years was regressed on percent protein intake, simultaneously adjusting
for other baseline factors: age, weight, height, weight change, total energy intake, smoking, alcohol intake,
caffeine, physical activity, calcium intake, and, for women, current estrogen use. Effects of animal protein on
bone loss also were examined. Mean age at baseline (؎SD) of 615 participants was 75 years (؎4.4; range,
68–91 years). Mean protein intake was 68 g/day (؎24.0; range, 14–175 g/day), and mean percent of energy
from protein was 16% (؎3.4; range, 7–30%). Proportional protein intakes were similar for men and women.
Lower protein intake was significantly related to bone loss at femoral and spine sites (p < 0.04) with effects
similar to 10 lb of weight. Persons in the lowest quartile of protein intake showed the greatest bone loss.
Similar to the overall protein effect, lower percent animal protein also was significantly related to bone loss
at femoral and spine BMD sites (all p < 0.01) but not the radial shaft (p ؍ 0.23). Even after controlling for
known confounders including weight loss, women and men with relatively lower protein intake had increased
bone loss, suggesting that protein intake is important in maintaining bone or minimizing bone loss in elderly
persons. Further, higher intake of animal protein does not appear to affect the skeleton adversely in this
elderly population. (J Bone Miner Res 2000;15:2504–2512)
Key words: protein intake, bone density, elderly, osteoporosis, longitudinal study
ically macronutrients, represent an important understudied
area in osteoporosis research.(4) Few studies have evaluated
diet and bone loss in free-living elders. Protein is of partic-
ular interest and concern because biochemical and nutri-
tional studies from as early as 1920,(5,6) and again more
recently,(7–10) have shown that high protein intake is a
powerful determinant of urinary calcium loss, which could
potentially upset calcium balance and lead to bone loss.
Despite the fact that several studies suggest a role for
protein in bone health, none has examined the effect of
levels of dietary protein on bone loss.
INTRODUCTION
STEOPOROSIS IS an important public health problem,
affecting 20–25 million Americans.(1–3) Although ma-
jor risk factors have been identified, dietary factors, specif-
O
*Presented in part as concurrent sessions at the 19th and 20th
Annual Scientific Meetings of the American Society of Bone and
Mineral Research, Cincinnati, Ohio, U.S.A. (1997) and San Fran-
cisco, California, U.S.A. (1998), as well as the Association of
Rheumatology Health Professionals at the 33rd Annual Scientific
Meeting, Washington, D.C., U.S.A. (1997).
1Hebrew Rehabilitation Center for Aged, Research and Training Institute and Harvard Medical School Division on Aging, Boston,
Massachusetts, U.S.A.
2Boston University School of Public Health, Boston, Massachusetts, U.S.A.
3Jean Mayer United States Department of Agriculture Human Nutrition Research Center on Aging at Tufts University, Boston,
Massachusetts, U.S.A.
4Boston University Arthritis Center, Boston, Massachusetts, U.S.A.
2504

DIETARY PROTEIN AND BONE LOSS
2505
Dietary protein can cause an increased acid load, which examination, subjects were asked to return for a callback
may be buffered by bone calcium. It is thought that the high examination to obtain BMDs at the lumbar spine. Results
sulfur content of meat may determine an endogenous acid from the baseline Framingham Osteoporosis Study have
load that contributes to bone loss. Sebastian et al. showed been reported previously.(22)
that bone loss in 18 postmenopausal women resulted from
mobilization of skeletal calcium salts used to balance acid
from dietary protein metabolism, and that increased acidity
stimulated bone resorption and inhibited bone formation
through suppression of osteoblast function.(11) The increase
in urinary calcium may depend on the amount and type of
protein intake because dietary acid load may be somewhat
influenced by the ratio of meat to vegetable protein intake,(4)
although the effect of type of protein intake on bone remains
unclear.(12–14)
As part of their regular clinic visit 4 years later (1992–
1993), 615 subjects (72%) who had baseline BMD and the
FFQ assessed had repeat BMD measures. All longitudinal
scan pairs were evaluated for consistency in anatomic site
and quality of analysis by the original technician, and those
scans showing inconsistencies were reanalyzed by two ex-
perienced investigators (M.T.H. and D.P.K.). Details on the
longitudinal follow-up osteoporosis examination have been
reported.(23) In brief, the mean 4-year BMD losses were
much greater for women than the losses for men. Annual-
ized rates of mean percent BMD loss are as follows: for
women, femoral neck loss was 0.87%, trochanter was
0.86%, Ward’s area was 1.06%, radial shaft was 1.21%, and
spine was 1.12%; for men, femoral neck loss was 0.38%,
trochanter was 0.04%, Ward’s area was 0.16%, radial shaft
was 0.90%, and spine was 0.09%.
Evidence also suggests that protein undernutrition is as-
sociated with osteoporosis. Low protein intake or insuffi-
ciency, perhaps a marker of total dietary insufficiency, has
been associated with frailty and fracture in the elderly.(15–17)
Evidence from a nursing home study of fractures and pro-
tein intake, although not controlling for confounders, sug-
gested that protein undernutrition may be associated with
osteoporotic fracture.(18) Thus, extreme levels of dietary
protein intake may pose a problem in elderly persons.
To our knowledge, no previous studies have addressed
the possible contributions of dietary protein to bone loss or
considered the effect of animal protein specifically in
population-based groups. Elderly persons are of particular
interest because they often suffer from chronic diseases and
may have a range of protein intakes below amounts previ-
ously linked to negative calcium balance. Thus, the purpose
of our study was to examine the association between dietary
protein and the skeletal health of elderly men and women.
We examined the relation between baseline dietary protein
and subsequent 4-year change in femoral, radial shaft, and
spine bone mineral density (BMD) for the elderly members
of the population-based Framingham Study. Further, our
study evaluated the effect of animal protein and nonanimal
protein intake for a possible effect on bone loss in older
individuals.
Our study was approved by the Boston University Insti-
tutional Review Board, and written informed consent was
obtained for all study subjects at both examinations.
Bone mineral density
BMDs of the proximal right femur (femoral neck, greater
trochanter, and Ward’s area) as well as the lumbar spine
(average BMD of L2–L4) were measured in grams per
square centimeter, using a Lunar dual photon absorptiome-
ter (DP3) at baseline and a dual X-ray absorptiometry
(DPX-L) densitometer (Lunar Radiation Corporation, Mad-
ison WI, U.S.A.) at the 4-year follow-up exam. We have
previously shown high correlations between dual photon
and dual X-ray absorptiometry.(24) However, because of a
small but consistent shift in BMD values between the two
technologies, femoral BMDs were adjusted for the change
in equipment from DP3 to DPX-L technology, using pub-
lished corrections.(24) Bone density at the proximal radial
shaft site was measured in grams per square centimeter
using a Lunar SP2 single photon absorptiometer (Lunar
Radiation Corporation) at both examinations. The right side
was scanned at each exam unless there was a history of
previous fracture or hip joint replacement. For these indi-
viduals, the left side was scanned. We used standard posi-
tioning as recommended by the manufacturer. Monthly
measurements of a bone phantom over the follow-up period
showed no machine drift across time. At the baseline ex-
amination, the coefficients of variation in normals measured
twice with repositioning for the DP3 were 2.6% (femoral
neck), 2.8% (trochanter), 4.1% (Wards area), 2% (radial
shaft), and 2.2% (lumbar spine). At examination 22, the
coefficients of variation for the DPX-L measurements were
1.7% (femoral neck), 2.5% (trochanter), 4.1% (Ward’s
MATERIALS AND METHODS
Study subjects
The population-based Framingham Cohort was estab-
lished in 1948 to examine risk factors for heart disease in
5209 men and women of ages 28–62 years.(19–21) Subjects
are seen biennially for a physical examination and a battery
of questionnaires and tests. Since the inception of the pri-
marily white cohort 50 years ago, nearly two-thirds of the
5209 cohort members have died. The surviving, now el-
derly, cohort subjects follow the same age- and sex-specific
population proportions found in the general Framingham
population.(22) At biennial examination 20 (1988–1989),
855 cohort members participated in the Framingham Osteo- area), and 0.9% (lumbar spine). We examined percent
porosis Study in which they had femoral BMD measure- change in BMD from baseline to 4-year follow-up. Percent
ments and proximal radial scans and completed a semiquan- change in BMD was calculated as the difference between
titative Food Frequency Questionnaire (FFQ). Because of exam 20 BMD and exam 22 BMD, divided by exam 20
the length of the routine biennial Framingham Study clinic BMD, and multiplied by 100.

2506
HANNAN ET AL.
Caffeine use, incorporating coffee and tea intake at base-
line, was defined as the sum of daily coffee (1 cup equals 1
caffeine unit) and daily tea (1 cup equals 0.5 caffeine units)
and grouped into 0–2 caffeine units consumed per day or
over 2 U/day.(29,30) Weekly use of beer, wine, or hard liquor
at baseline was grouped into ounces of alcohol consumed
per week based on Framingham calculations of intake.(31,32)
Physical activity at baseline was defined using the Framing-
ham Physical Activity Index, a weighted 24-h score of
typical daily activity, based on hours spent doing heavy,
moderate, light, or sedentary activity as well as sleep-
ing.(33,34) Baseline dietary calcium intake, including cal-
cium supplements, was assessed from the FFQ and evalu-
ated as milligrams per day of calcium. For women, current
use of oral conjugated estrogen, patch, or cream at or within
a year of the baseline examination was determined from the
baseline Framingham Study questionnaire. Estrogen use
was defined as current users versus noncurrent users (in-
cluding both former and never users), based on prior work
showing effects only for current estrogen use in elderly
women.(35) Too few of the elderly women were current
users to adjust further for dose of estrogen use.
Food Frequency Questionnaire
Dietary intake was assessed using the 126-item Willett
FFQ(25,26) at the baseline examination in 1988–1989 and
these data were converted to food and nutrient intake data.
Individuals who reported intakes of less than 600 or greater
than 4000 kcal or with data missing for more than 12 food
items were excluded. The Willett FFQ has been validated,
and nutrient intakes have been shown to correlate well with
those obtained by multiple food records and with blood
measures for several nutrients.(26,27) However, it is only
semiquantitative in nature, and translation of results to
quantitative recommendations remains to be validated for a
number of nutrients. Nevertheless, the Willett FFQ has been
shown to rank individuals well in relation to their actual
intake. In general, usual intake patterns examined for the
purpose of ranking individuals for association with an out-
come measure, typically are best measured with an FFQ.
The Willett FFQ has been validated extensively and has
been shown to be reproducible in the long term for both
cohorts of men(25) and women,(26) showing that the FFQ is
a stable and reproducible measure of ranking for food
intakes. As Willett points out,(28) the underlying principle of
an FFQ is that average long-term diet intake is the concep-
tually important exposure rather than short-term intake
across a few specific days. FFQ methodology therefore
estimates usual intakes over the past year indicating typical
long-term intakes rather than providing precise measure-
ments of short-term intake. To evaluate whether protein
intakes may change over time, we examined the change in
rank from the FFQ measured at baseline in our study to
another measurement of FFQ 2 years later. There were only
minor changes reported in intakes, such that no one in our
study changed quartile of protein intake.
Statistical analyses
Baseline characteristics were compared using Student’s
2
t-tests or ␹ tests as appropriate. We evaluated each BMD
site separately, using linear regression to examine the rela-
tion of change in BMD with percent protein intake with
simultaneous adjustment for potential confounding vari-
ables. Because total energy intake is correlated with most
nutrients, we adjusted for total energy intake to assess the
independent effect contributed by protein. By doing so,
possible differences in intake caused by body size or activ-
ity levels also are taken into account.(28,36) The model
evaluated BMD change over the 4 years as a function of
Protein intake
Dietary protein intake was expressed as percent of energy percent protein intake, total energy intake, age, sex, and the
from protein (percent protein). Further, components of pro- major known risk factors for bone loss: weight, weight
tein were divided into animal and nonanimal protein intake change, height, smoking, and alcohol use. We further ad-
and expressed as percent of energy from animal protein and justed for the potential additional effects of physical activ-
percent from nonanimal protein.
Potential confounding variables: We controlled for the (yes/no).
influence of the following factors at baseline on the relation We examined the effect of protein intake in the BMD
ity, calcium intake, and for women, current estrogen use
between dietary protein intake and bone loss at each skeletal models using several well-established statistical methods(28)
site: total energy intake, age, sex, weight, height, smoking, (1) the residual method, regressing protein grams of intake
caffeine, alcohol use, physical activity, calcium intake, and on total energy intake and used these residuals in the BMD
for women current estrogen use. We also included a well- analyses; (2) the nutrient density model, adjusting grams of
known risk factor for bone loss: weight change over the protein intake for total energy intake in standard multivar-
4-year follow-up. Weight in pounds (converted to kilo- iate model; (3) the energy decomposition model, adjusting
grams) was measured at baseline using a standardized bal- protein intake for the total nonprotein energy intake; and,
ance beam scale and weight at follow-up was measured finally, (4) protein not adjusted for total energy. Because all
similarly using the same calibrated scale. In addition to these methods provided very similar results, only the results
baseline weight, we included percent weight change over from the analyses using percent protein adjusted for total
the follow-up as a continuous variable. Height (without energy will be presented.
:
shoes) was measured in inches using a stadiometer and
We evaluated percent protein as a continuous variable
1
recorded to the nearest ⁄
4
inch. A participant’s smoking and as quartiles of intake, to evaluate the possibility of a
status was assessed via questionnaire at baseline and pre- nonlinear relation. The quartile analysis presents the protein
ceding examinations as current cigarette smoker at baseline and BMD relation across the intake ranges seen in a popu-
(smoked regularly in the past year), former smoker, or never lation setting to examine the effect of possible levels of
smoked.
protein intake on BMD loss, because it is unclear what

DIETARY PROTEIN AND BONE LOSS
2507
TABLE 1. COMPARISON OF BASELINE CHARACTERISTICS IN FRAMINGHAM COHORT MEMBERS WITH DIETARY FFQ DATA
a
WHO ATTENDED BOTH BASELINE AND FOLLOW-UP EXAMINATIONS TO THOSE MEMBERS WHO ONLY
ATTENDED BASELINE EXAMINATION
Attended
both exams
(n ϭ 615)
Attended only
baseline exam
(n ϭ 240)
Characteristics
Age (years)b
p Value
74.5 Ϯ 4.4
(68–91)
70.6 Ϯ 14.7
(41–148)
77.2 Ϯ 5.3
(67–93)
68.4 Ϯ 13.2
(40–122)
0.001
(range)
Weight (kg)b
0.04
(range)
Percent female
Protein intake (g/day)b
% Protein per day
Animal protein
Protein (g/kg per day)
Energy intake
64%
55%
0.01
0.41
0.27
0.56
0.88
0.96
68.5 Ϯ 23.6
15.9 Ϯ 3.4
45.7 Ϯ 19.1
1.00 Ϯ 0.39
1736 Ϯ 572
66.8 Ϯ 24.4
15.6 Ϯ 3.35
44.85 Ϯ 19.1
1.00 Ϯ 0.42
1732 Ϯ 620
BMD (g/cm2)b
Radial shaft
0.594 Ϯ 0.134
0.789 Ϯ 0.144
0.709 Ϯ 0.161
0.606 Ϯ 0.149
1.169 Ϯ 0.231
10%
47%
43%
2.5 Ϯ 3.72
810 Ϯ 437.0
0.585 Ϯ 0.136
0.763 Ϯ 0.154
0.690 Ϯ 0.178
0.587 Ϯ 0.173
1.167 Ϯ 0.280
13%
47%
40%
2.3 Ϯ 3.92
783 Ϯ 417.0
0.35
0.03
0.14
0.16
0.91
0.36
Femoral neck
Trochanter
Ward’s area
Lumbar spine
Percent current smoker
Former smoker
Never smoker
Alcohol intake (oz/week)b
Calcium intake (mg/day)b
Women only
0.61
0.40
Current estrogen use
Ever used estrogen
7.0%
38.7%
3.0%
33.8%
0.09
0.31
a Number for attendees based on having either femoral or radial shaft BMD scan at both exams.
b Mean at baseline Ϯ SD.
intake levels may cause concern in the elderly. Men and members without follow-up data (the majority of whom
women had similar distributions of overall protein intake died during the follow-up period) tended to be older, of
and animal protein intake, as well as similar relations be- lower weight, and male, with baseline BMDs slightly lower
tween protein intake and BMD change. There were no sex than those followed (e.g., femoral neck BMD, 0.763 vs.
by protein interactions in models for any bone site. Thus, 0.789 and p ϭ 0.02); however, their baseline protein intakes
analyses for men and women were combined. For the quar- did not differ from cohort members with 4-year follow-up
tile analyses, adjusted mean BMDs are presented (least (Table 1). Participants and nonparticipants had similar dis-
squares means Ϯ SE), for levels of protein intake resulting
from the analysis of covariance (ANCOVA). All analyses
used the SAS statistical analysis package (release 6.12; SAS
Institute Inc., Cary, NC, U.S.A.). Models of the absolute
change in BMD from baseline examination to follow-up
examination showed similar results as the percent change
analyses, and, thus, the absolute change analyses are not
presented here. First, we evaluated the impact of dietary
protein intake on bone loss. Second, we examined the
influence of animal protein versus nonanimal protein in-
takes.
tributions for smoking, alcohol intake, and calcium intake.
Table 2 shows the distributions for mean protein intake as
well as percent of energy from protein by sex. Mean protein
intake for the participants was 68 Ϯ 23.6 g/day (SD) with a
range from 17 to 152 g/day. Protein comprised 16%
(Ϯ3.4%; range, 7–27%) of total energy intake. Percent of
energy from animal protein was 10% (Ϯ3.5%).
Baseline BMD values at the femoral neck, trochanter,
Ward’s area, radial shaft, and lumbar spine were not sig-
nificantly associated with protein intake, with p values rang-
ing from 0.30 (trochanter and radius) to 0.54 (Ward’s area).
Mean 4-year BMD losses have been reported,(23) and for
women, ranged from Ϫ4.84% (radial shaft) to Ϫ3.42%
(trochanter), while losses for men ranged from Ϫ3.59%
(radial shaft) to Ϫ0.17% (trochanter).
RESULTS
For the 615 subjects (391 women and 224 men) with
Overall dietary protein intake: Lower percent protein
longitudinal data, the mean age (ϮSD) at baseline was 75 intake was significantly related to greater BMD loss at all
years (Ϯ4.4 years) with a range from 68 to 91 years. Cohort femur and spine sites (all p Ͻ 0.02), but not at the radial

2508
HANNAN ET AL.
TABLE 2. DISTRIBUTIONS OF TYPES OF DIETARY PROTEIN INTAKE BY SEX
Protein intake
Total
Men (n ϭ 224)
Women (n ϭ 392)
Protein intake (g/day)
Mean (ϮSD)
Quartile 1 low
68 Ϯ 23.6
17–51
69.3 Ϯ 23.9
21–53
68.0 Ϯ 23.5
16–50
2
52–67
54–69
51–65
3
68–83
70–83
66–81
4 high
84–152
84–146
82–153
Protein intake (g/kg per day)
Mean (ϮSD)
Quartile 1 low
1.00 Ϯ 0.39
0.21–0.71
0.72–0.96
0.97–1.23
1.24–2.78
0.89 Ϯ 0.33
0.27–0.63
0.64–0.87
0.88–1.05
1.06–1.89
1.07 Ϯ 0.40
0.21–0.77
0.78–0.99
1.00–1.30
1.31–2.78
2
3
4 high
Percent energy from protein (of
total caloric intake per day)
Mean % (ϮSD)
Quartile 1 low
15.9 Ϯ 3.3
7.3–13.5
15.0 Ϯ 3.3
7.3–12.9
16.3 Ϯ 3.4
8.1–14.2
2
3
13.7–15.7
15.8–17.8
17.9–27.4
13.0–15.0
15.1–17.1
17.2–26.9
14.3–16.1
16.2–18.3
18.4–27.4
4 high
Animal protein intake (g/day)
Mean (ϮSD)
Quartile 1 low
45.7 Ϯ 19.1
4–32
45.5 Ϯ 18.8
6–33
45.8 Ϯ 19.3
4–32
2
33–43
34–44
33–43
3
44–57
45–57
44–57
4 high
58–132
58–111
58–132
Percent animal protein intake (of
total caloric intake per day)
Mean % (ϮSD)
Quartile 1 low
10.6 Ϯ 3.5
1.9–8.2
9.9 Ϯ 3.3
2.1–7.6
11.0 Ϯ 3.5
1.9–8.5
2
3
8.3–10.3
10.4–12.5
12.6–23.4
7.7–9.7
9.8–11.7
11.8–23.4
8.6–10.9
11.0–13.0
13.1–22.8
4 high
shaft (p ϭ 0.26). After adjusting for the major risk factors showed the least BMD loss across follow-up. Again, further
for osteopenia, lower percent protein intake remained sig- adjustment for physical activity, calcium intake, and for
nificantly related to greater BMD loss at the femoral neck women, current estrogen use, did not alter these results.
(␤ ϭ 0.203; p ϭ 0.02), Ward’s area (␤ ϭ 0.266; p ϭ 0.04),
Animal protein intake: Similar to the overall protein
and spine (␤ ϭ 0.281; p ϭ 0.02) with regression coefficients effect, lower percent of energy from animal protein also was
at all three sites comparable with 10 lb of weight or a significantly related to bone loss at all femoral and spine
smoking effect, both well-established risk factors for os- BMD sites (all p Ͻ 0.01) but not the radial shaft (p ϭ 0.23).
teopenia. The p values for all the overall global ANCOVA Percent of energy from nonanimal protein did not contribute
models ranged from 0.0001 for the femoral neck and lumbar to these BMD models (p value range, 0.79–0.98). When
spine to 0.0628 for the radial shaft. Further adjustment for these models were adjusted for the major risk factors for
physical activity, calcium intake, and for women, current osteopenia, the relation between BMD change and animal
estrogen use, did not alter the effect of protein intake on protein intake remained statistically significant (femoral
change in BMD.
neck, p ϭ 0.03; lumbar spine, p ϭ 0.02) in a manner
When quartiles of percent protein intake were evaluated, consistent with the overall protein effect described previ-
the lowest protein quartile showed the greatest bone loss. ously. Again, further adjustment of the model for physical
(Fig. 1). Similar results were seen at the other femur sites activity, calcium intake, and for women, current estrogen
and the lumbar spine, with a similar trend observed for the use, did not alter the results.
radial shaft. When the relation between BMD loss and
When percent animal protein quartiles were evaluated,
protein was adjusted for the major known risk factors for the lowest quartile showed the greatest bone loss (Fig. 2),
bone loss—weight, weight change, height, age, sex, smok- similar to the overall protein intake results for quartiles,
ing, and alcohol use—the lowest quartile of protein contin- although no relation was seen between radial shaft bone loss
ued to have the greatest BMD loss (Table 3). The highest and animal protein intake. Table 4 displays the least squares
quartile, with protein intakes of 1.24–2.78 g/kg. per day, mean results for all BMD sites and, again, these results

DIETARY PROTEIN AND BONE LOSS
2509
A number of studies(4,39–41) reported that a doubling of
protein intake increases urinary calcium loss by 50%. Parfitt
also noted that the acid load from dietary protein is partially
buffered by skeletal bone loss, accounting for a portion of
age-related bone loss.(42) Allen reported that urinary cal-
cium loss is correlated directly with dietary intake of protein
and that high calcium diets do not prevent the negative
calcium balance and bone loss induced by a diet high in
protein,(43) although it is unclear what levels of protein
intake would be considered high for this population. The
influence of dietary protein metabolically may be not as
great in the elderly as one would assume, based on esti-
mated intake, because additional age-related changes in
renal function and intestinal absorption influence calcium
imbalance.(44) Although these studies examined short-term
calcium loss, several cross-sectional studies of forearm
BMD and protein intake reported no association between
dietary protein and BMD.(14,45)
FIG. 1. Mean percent bone loss over 4 years (ϮSE) at hip,
spine, and radius by quartiles of protein intake (Framingham
Osteoporosis Study).
Our findings are in agreement with two papers reporting
better bone health in women with greater protein intakes.
Freudenheim et al.(46) showed that high protein intake pro-
tected against low radius BMD in older women. Munger et
al. found an increased risk of hip fracture in elderly women
consuming the lowest amounts of protein in the Iowa Wom-
en’s Health Study.(47) Further, the Munger study reported
that higher intakes of animal sources of dietary protein were
associated with a 70% reduction in hip fracture, even after
controlling for major confounding variables.
parallel those seen in Table 3. None of the BMD sites
indicated a relation between BMD and nonanimal protein.
Figure 3 shows the lack of a relation between nonanimal
protein intakes (quartiles) and bone loss at the femoral neck.
DISCUSSION
The mean protein intake of 68 g/day and percent protein
A number of studies support the adverse role of low
intake of 16% for the study participants are similar to protein intake on bone metabolism. Hirota et al.(48) reported
recommendations for total protein and percent of energy that low protein intake in young Asian women was a risk
from protein set by the U.S. Government and also similar to factor for low forearm BMD in their study of 161 women
other reported values.(37,38) The current recommended daily ages 19–25 years. Similarly, Geinoz et al.,(49) in a study of
allowance (RDA) for protein intake is 0.8 mg/kg, and 74 hospitalized geriatric patients (mean age, 82 years),
roughly 32% of the Framingham Cohort have protein intake showed that low dietary protein intake was associated with
below this RDA; however, 90% have an intake at least low femoral BMD. Additional studies of protein supple-
two-thirds of the RDA (two-thirds of RDA is a common mentation in elderly women posthip fracture clearly showed
cut-off used to estimate dietary adequacy, because the RDA benefit in terms of BMD and muscle strength,(50,51) imply-
contains a margin of error to cover most healthy individu- ing that protein insufficiency, particularly in the oldest of
als). In our study, both lower protein intake and lower old, contributes to osteoporosis. In addition, two studies
animal protein intake were significantly related to greater reported that hip fracture patients had diets particularly
BMD loss at femur and spine BMD sites. Even after ad- deficient in protein and energy.(17,18) Kerstetter et al. show
justment for the major risk factors for bone loss, including that low protein intake may induce secondary hyperpara-
weight, weight loss, and smoking, lower, but not higher, thyroidism, perhaps inducing loss of bone.(52,53) Indeed,
protein intake remained significantly related to greater there is potential for interventions with protein intakes.
BMD loss at the femur and spine with effects comparable Schurch et al. conducted a 6-month randomized clinical trial
with 10 lb of weight or a smoking effect, both well- of protein supplementation of 20 g/day in hip fracture
established risk factors for osteopenia. Those elders with patients and showed 50% attenuation in femoral bone loss
higher protein intake had reduced bone loss, suggesting that after 1 year of follow-up.(54)
protein intake is important in maintaining bone or minimiz-
ing bone loss in elderly persons.
Orwoll et al. examined vertebral and radius BMDs and
reported that protein undernutrition, as assessed by serum
Contrary to expectations, elders with animal protein in- albumen measures, was associated with osteopenia, and that
take up to several-fold greater than the RDA also had the low dietary protein intakes possibly influence bone metab-
least bone loss after controlling for known confounders. olism.(55) They noted that although excess dietary protein
Nonanimal sources of protein were not related to BMD. has been shown to cause negative calcium balance, this
These results suggest that typical population intakes of occurs primarily with extremely high levels of protein, not
animal protein, within the range commonly consumed, do often seen in the elderly who are at the highest risk for
not result in bone loss. Rather animal protein intake appears osteoporosis. Indeed, Chu et al., in a trial that doubled the
important in maintaining bone or minimizing bone loss in typical protein intake in elders, reported that rather than
elderly persons.
causing negative calcium balance, the increased protein

2510
HANNAN ET AL.
TABLE 3. QUARTILES OF PERCENT PROTEIN INTAKE BY ADJUSTED LEAST SQUARES MEAN PERCENT BMD
CHANGE AT HIP, SPINE, AND RADIUS SITES
Site
Quartile 1
Quartile 2
Quartile 3
Quartile 4
Femoral neck
Trochanter
Ward’s area
Lumbar spine
Radius
Ϫ4.61 Ϯ 0.70*
Ϫ8.00 Ϯ 0.84
Ϫ7.05 Ϯ 1.0†
Ϫ3.72 Ϯ 0.97†
Ϫ4.21 Ϯ 0.71
Ϫ3.68 Ϯ 0.71‡
Ϫ7.70 Ϯ 0.86
Ϫ6.14 Ϯ 1.0
Ϫ1.76 Ϯ 1.0
Ϫ5.33 Ϯ 0.73
Ϫ3.05 Ϯ 0.73
Ϫ7.28 Ϯ 0.89
Ϫ5.41 Ϯ 1.0
Ϫ2.40 Ϯ 1.0
Ϫ3.82 Ϯ 0.75
Ϫ2.32 Ϯ 0.74
Ϫ6.65 Ϯ 0.90
Ϫ4.39 Ϯ 1.1
Ϫ1.11 Ϯ 1.1
Ϫ4.31 Ϯ 0.76
Model adjusted for total energy intake, age, sex, weight, weight change, height, alcohol intake and smoking (current or former).
Each quartile compared with quartile 4: *0.001 Ͻ p Ͻ 0.0001; †0.05 Ͻ p Ͻ 0.01; ‡0.10 Ͻ p Ͻ 0.05.
intake. Finally, the finding of a consistent protein effect at
multiple bone sites after control of potential confounders
strongly suggests that adequate protein intake is important
to skeletal health of aged persons.
Several limitations also should be noted. The data do not
take into account possible longer-term effects of certain risk
factors (e.g., cumulative effect of smoking or medications).
Second, different technology assessed femoral BMD at
baseline and follow-up, although data were “standardized.”
Finally, we cannot derive precise protein intake values
representing the lowest threshold, because we used an FFQ
that typically best ranks individuals’ dietary intakes.
As the population ages, osteoporosis will escalate in
importance as a major public health problem. This study
suggests an important, potentially modifiable factor that
FIG. 2. Mean percent bone loss over 4 years (ϮSE) at hip,
spine, and radius by quartiles of animal protein intake
could have major implications for the diets of millions of
(Framingham Osteoporosis Study).
men and women as well as affect their risk of osteoporosis.
Our results indicate that low protein intake is associated
with BMD loss. Campbell et al.(57) make a compelling
intakes improved the calcium balance in the majority of
argument that the protein RDA for older persons in the
their subjects.(56) These studies raise the possibility that low
United States, established from extrapolations from healthy
protein intakes, particularly in the elderly, may adversely
young men, is too low. Based on several protein require-
affect bone mineral metabolism.
ment studies of elderly subjects, they recommend a safe
These studies, when considered together, suggest that
protein intake to range from 1.0 to 1.25 g/kg per day. These
adequate protein nutriture is required for bone health. Met-
values would correspond roughly to the third quartile in our
abolic studies showing that high intakes of protein may have
analyses. A metabolic balance study(58) and a nutritional
an adverse consequence on calcium balance have all been of
status survey of elders over the age of 65 years(59) also
short-term duration. It remains unclear what the long-term
provide strong support that elders have a higher protein
influences of protein intake and its possible acid load have
requirement than that currently recommended. Even so, the
on bone. It may well be that only extreme excess protein
U.S. Department of Agriculture (USDA) data on nutrition
intake or deficient protein intake may be deleterious yet
report that 30% of all adult women are below the RDA for
uncommon problems in human populations. Our results
protein and over 25% of the Framingham cohort have
suggest that within the normal variation in dietary protein of
protein intake below the current RDA of 0.6 g/kg. If the
this population of elders low protein intake is associated
protein intake sufficiency threshold is even higher for elders
with BMD loss, while higher (normal) protein intake is
than the current RDA, low protein intake may place many
associated with reduced bone loss or with maintenance of
BMD.
This study has several unique strengths. First, the Fra-
mingham cohort is population based, rather than a study of
volunteers or those who already have disease. Second, the
longitudinal design provides important information about
factors responsible for bone loss in old age. Third, unlike
most studies of osteoporosis, it includes a large number of
men as well as women who have longitudinal BMD mea-
surements. Fourth, this study has comprehensive dietary
elders at risk for bone loss.
This population-based study suggests that dietary protein
intake is an important component of bone health in elders,
showing an effect for both women and men with age-related
bone loss, even after controlling for major known confound-
ers. Further, this study indicates that high levels of dietary
protein intake, within the range commonly consumed, do
not result in bone loss in elders. Ensuring adequate dietary
protein intake is an important component of bone health in
assessments that have shown to estimate usual nutrient elders.

DIETARY PROTEIN AND BONE LOSS
2511
TABLE 4. QUARTILES OF PERCENT ANIMAL PROTEIN INTAKE AND ADJUSTED LEAST SQUARES MEAN PERCENT BMD CHANGE
AT HIP, SPINE, AND RADIUS SITES
Site
Quartile 1
Quartile 2
Quartile 3
Quartile 4
Femoral neck
Trochanter
Ward’s area
Lumbar spine
Radius
Ϫ3.95 Ϯ 0.69*
Ϫ2.57 Ϯ 0.86
Ϫ4.02 Ϯ 1.0†
Ϫ3.79 Ϯ 0.99†
Ϫ4.60 Ϯ 0.71
Ϫ3.83 Ϯ 0.72*
Ϫ3.25 Ϯ 0.89
Ϫ3.90 Ϯ 1.1
Ϫ2.55 Ϯ 1.0
Ϫ4.35 Ϯ 0.73
Ϫ3.02 Ϯ 0.73
Ϫ1.75 Ϯ 0.91
Ϫ2.03 Ϯ 1.1
Ϫ1.24 Ϯ 1.0
Ϫ4.39 Ϯ 0.77
Ϫ2.15 Ϯ 0.73
Ϫ1.95 Ϯ 0.92
Ϫ1.97 Ϯ 1.1
Ϫ1.65 Ϯ 1.1
Ϫ4.52 Ϯ 0.76
Model adjusted for total energy intake, nonanimal protein intake, age, sex, weight, weight change, height, alcohol intake and smoking
(current or former).
Each quartile compared with quartile 4: *0.05 Ͻ p Ͻ 0.01; †0.10 Ͻ p Ͻ 0.05.
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ACKNOWLEDGMENTS
We are grateful to the Framingham cohort participants 15. Patterson B, Cornell CN, Carbone B, Levine B, Chapman D
1992 Protein depletion and metabolic stress in elderly patients
who have a fracture of the hip. Am J Bone Joint Surg 74:251–
260.
and staff, and we also thank the densitometer technicians
Mimi Brodsky, Mary Hogan, and Cherlyn Mercier. This
work was supported in part by a New Investigator Award
from the Arthritis Foundation, National Institutes of Health
(NIH) grants RO1-AR/AG41398 and AR20613, and U.S.
Department of Agriculture (USDA) Agricultural Research
Service (ARS) contract number 53-3K06-01.
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Marian T. Hannan
Hebrew Rehabilitation Center for Aged Research
and Training Institute
1200 Center Street
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