JOURNAL OF BONE AND MINERAL RESEARCH

Volume 15, Number 4, 2000

© 2000 American Society for Bone and Mineral Research

Risk Factors for Longitudinal Bone Loss in Elderly Men

and Women: The Framingham Osteoporosis Study

MARIAN T. HANNAN,1,4 DAVID T. FELSON,2,4 BESS DAWSON-HUGHES,3 KATHERINE L. TUCKER,3

L. ADRIENNE CUPPLES,4 PETER W.F. WILSON,5 and DOUGLAS P. KIEL1

ABSTRACT

Few studies have evaluated risk factors for bone loss in elderly women and men. Thus, we examined risk
factors for 4-year longitudinal change in bone mineral density (BMD) at the hip, radius, and spine in elders.
Eight hundred elderly women and men from the population-based Framingham Osteoporosis Study had BMD
assessed in 1988 –1989 and again in 1992–1993. BMD was measured at femoral neck, trochanter, Ward’s area,
radial shaft, ultradistal radius, and lumbar spine using Lunar densitometers. We examined the relation of the
following factors at baseline to percent BMD loss: age, weight, change in weight, height, smoking, caffeine,
alcohol use, physical activity, serum 25-OH vitamin D, calcium intake, and current estrogen replacement in
women. Multivariate regression analyses were conducted with simultaneous adjustment for all variables.
Mean age at baseline was 74 years 6 4.5 years (range, 67–90 years). Average 4-year BMD loss for women
(range, 3.4 – 4.8%) was greater than the loss for men (range, 0.2–3.6%) at all sites; however, BMD fell with age
in both elderly women and elderly men. For women, lower baseline weight, weight loss in interim, and greater
alcohol use were associated with BMD loss. Women who gained weight during the interim gained BMD or had
little change in BMD. For women, current estrogen users had less bone loss than nonusers; at the femoral neck,
nonusers lost up to 2.7% more BMD. For men, lower baseline weight and weight loss also were associated with
BMD loss. Men who smoked cigarettes at baseline lost more BMD at the trochanter site. Surprisingly, bone
loss was not affected by caffeine, physical activity, serum 25-OH vitamin D, or calcium intake. Risk factors
consistently associated with bone loss in elders include female sex, thinness, and weight loss, while weight gain
appears to protect against bone loss for both men and women. This population-based study suggests that
current estrogen use may help to maintain bone in women, whereas current smoking was associated with bone
loss in men. Even in the elderly years, potentially modifiable risk factors, such as weight, estrogen use, and
cigarette smoking are important components of bone health. (J Bone Miner Res 2000;15:710 –720)

Key words: bone density, elderly, osteoporosis, longitudinal study, risk factors

INTRODUCTION menopausal women; however, bone density in elderly

persons is highly relevant to the risk of osteoporotic
data exist on bone mineral density fracture.(1–7) About 26 million white women in the United
L ITTLE LONGITUDINAL
(BMD) changes in the elderly. Bone density studies
have focused primarily on perimenopausal and early post-
States have low bone mass, and their lifetime risk of
osteoporosis-related fractures exceeds 40%.(8,9) The highest

1
Hebrew Rehabilitation Center for Aged, Research and Training Institute and Harvard Medical School Division on Aging, Boston,
Massachusetts, U.S.A.
2
Boston University Arthritis Center, Boston, Massachusetts, U.S.A.
3
Jean Mayer Human Nutrition Research Center on Aging at Tufts University, Boston, Massachusetts, U.S.A.
4
Department of Epidemiology and Biostatistics, Boston University School of Public Health, Boston, Massachusetts, U.S.A.
5
National Heart Lung and Blood Institute’s Framingham Heart Study, Framingham, Massachusetts, U.S.A.

710
RISK FACTORS FOR LONGITUDINAL BONE LOSS IN ELDERS
rates of osteoporosis-related fractures occur in elderly
women, although 13% of men also will experience such
fractures. Low bone density in the femur is a strong predic-
tor of the increased risk for hip fracture. In one of the largest
cohort studies of osteoporosis, the Study of Osteoporotic
Fractures, women in the lowest quartile of BMD had an
8-fold increased risk of hip fracture compared with the
women in the highest BMD quartile.(4) Slowing age-related
bone loss may lead to the prevention of a considerable
number of fractures. Despite the importance of bone density
in the elderly, very little is known about change in bone
density of elders and the relative importance of traditional
osteoporosis risk factors.
Bone loss, at least at the femur and radius, continues in
the elderly years, even past the age of 85 years.(10 –18) Our
earlier cross-sectional study of femoral and radius BMD in
the Framingham cohort found that age was inversely related
to BMD in both men and women.(10) Both cross-sectional
and longitudinal studies also have reported age-related bone
loss.(11–15,17,18) Nevertheless, few studies have examined
risk factors for bone loss in elders. It is unknown whether
factors affecting bone loss in postmenopausal women are
similar for elderly men and women. The population at
greatest risk for fracture is the elderly, and thus the greatest
public health impact would stem from preventing bone loss
in this group.
To evaluate how bone density changes in older persons
over time, we examined the longitudinal change in BMD at
several anatomic sites for the elderly men and women of the
Framingham study, a population-based cohort. Our study
further queried whether lifestyle factors and anthropometric
variables might be important risk factors for subsequent
bone loss. The purpose of our study was to evaluate the
relation between baseline risk factors and 4-year BMD loss
at several skeletal sites for the now elderly Framingham
cohort men and women.
METHODS
Study subjects
The population-based Framingham was established in
1948 with the primary aim of examining risk factors over
time for heart disease in 5209 men and women 28 – 62 years
old.(19 –21) Subjects, nearly all white, are seen biennially for
a physical examination and a battery of questionnaires and
tests. Since the establishment of the cohort 50 years ago,
nearly two-thirds of the 5209 cohort members have died.
The surviving, now elderly, cohort subjects follow the same
age- and sex-specific population proportions found in the
general population of Framingham, MA.(10) At biennial
examination 20 (1988 –1989), 1164 cohort members partic-
ipated in the Framingham Osteoporosis Study, including
nursing home residents who were ambulatory. In the osteo-
porosis study group, 1142 members obtained valid proximal
radial shaft scans and 1102 members obtained valid femoral
BMD measurements. Because of length of the routine bi-
ennial Framingham study clinic examination, subjects were
asked to return to a callback examination to obtain BMDs at
additional skeletal sites. Lumbar spine and ultradistal radius
711
scans were obtained at examination 20 as a callback to the
regular clinic examination with 842 subjects having a lum-
bar spine scan and 882 subjects having the ultradistal radius
scan. Details from the baseline Framingham osteoporosis
study at biennial examination 20 have been reported.(10)
As part of their regular clinic visit at biennial examination
22 (1992–1993), 800 subjects (69%) who had baseline
BMD assessed at examination 20 had follow-up radial shaft
and/or femoral BMD measures approximately 4 years later.
All longitudinal scan pairs were evaluated for consistency
of anatomic site and quality of analysis by the original
technician, and those scans showing inconsistencies were
reanalyzed by two experienced investigators (M.T.H. and
D.P.K.). Of these 800 subjects with longitudinal scans, 780
cohort members had valid radial shaft BMD measures and
758 subjects had valid repeat hip BMD scans. As in the
baseline osteoporosis study, we conducted a callback com-
ponent to evaluate bone density in the ultradistal radius and
spine at biennial examination 22. At this callback examina-
tion, 567 members had repeat spine scans and 557 subjects
had repeat ultradistal radius scans. Seventeen femur scans
and 16 arm scans were performed on the contralateral side
at follow-up and thus were not considered valid scans for
the longitudinal analysis. Our study was approved by the
appropriate institutional review board, and written informed
consent was obtained for all study subjects at both exami-
nations.
BMD
Bone density was measured at the 33% radial shaft site
and at the ultradistal radius site in grams per centimeter
squared using a Lunar SP2 single-photon absorptiometer
(Lunar Radiation Corporation, Madison, WI, U.S.A.) at
both examinations. The ultradistal radius site includes both
radius and ulna bones at the radial/ulna interface per man-
ufacturer. Quality control scans indicated no shift in BMD
because of equipment or change in radioactive source over
the 4 years of follow-up. BMDs of the proximal right femur
(femoral neck, greater trochanter & Ward’s area), as well as
the lumbar spine, were measured in grams per centimeter
squared using a Lunar dual-photon absorptiometer (DP3)
(Lunar Radiation Corporation) at biennial exam 20 and a
dual X-ray absorptiometry (DPX-L) densitometer at exam
22. The right side was scanned at each exam unless there
was a history of previous fracture or hip joint replacement,
in which case, the left side was scanned. The lumbar spine
BMD represents the average BMD of L2–L4. We used
standard positioning as recommended by the manufacturer,
including medial rotation of the femur to ensure a clear scan
of the femoral neck region. Monthly measurements of a
bone phantom over the follow-up period showed no ma-
chine drift across time. The CV in normals over the 2 years
of the baseline examination for the DP3 was 2.6 (femoral
neck), 2.8 (trochanter), and 4.1 (Wards area). The proximal
radial shaft CV was 2% using young normal controls; the
ultradistal radius CV was 5.7%; and the CV of the lumbar
spine was 2.2%. Details of the measurements taken in
1988 –1989 at examination 20 were published previous-
ly.(10) We used 21 cohort members measured twice with
712
repositioning to evaluate the CV for the DPX-L measure-
ments at examination 22, finding the CV for the femoral
neck of 1.7%, for the trochanter 2.5%, for the Ward’s area
4.1%, and for the lumbar spine 0.9%. We previously
showed high correlations between dual-photon and dual
X-ray absorptiometry.(22) However, because of a small but
consistent shift in BMD values between the two technolo-
gies, femoral BMDs were adjusted for the change in equip-
ment from DP3 to DPX-L technology, using published
corrections, based on cross calibrations of the two instru-
ments using our Framingham study subjects.(22) All scans
were examined for correct analysis and placement of the
region of interest (ROI) analysis box. The specific quality
control protocols used to ensure comparability between
longitudinal scans included re-examination of all outlier
BMD values and re-examination of all longitudinal femur
scan pairs with a 5% or greater difference in the area
included in the femoral neck ROI box, to ensure that the
analyzed region was similarly placed for each pair of lon-
gitudinal scans. When necessary, this ROI box was reposi-
tioned to more closely approximate the baseline femoral
neck ROI area.(22) Any scans with metal or other attenuating
material in the region of interest as well as any scans of poor
quality were deleted. The quality control protocol resulted
in several scans of poor quality being dropped from the
analysis, as well as the deletion of nine femoral trochanteric
BMD values in which the bone edges for at least one of the
paired trochanter scans were cut off during the scan data
collection, resulting in an incorrect trochanter BMD value.
Risk factors
We examined the relation of the following factors at
baseline (examination 20) to BMD loss at each skeletal site
over the 4-year follow-up. The effect of age at baseline was
examined in 5-year age groups as well as in continuous
units. Weight was measured at examinations 20 and 22
using a standardized balance beam scale. In addition to
analyzing weight on a continuous scale, we divided weight
at baseline into sex-specific quartiles for analysis. Percent
change in weight over the study interval was defined as the
difference between exam 20 weights and exam 22 weights,
divided by exam 20 weight and multiplied by 100. Percent
weight change over the follow-up was categorized into three
groups: weight loss greater than 5%, weight loss or gain of
no more than 5% (referent group), and weight gain greater
than 5%. Height (without shoes) was measured to the near-
est one-fourth inch using a stadiometer and analyzed both as
continuous and by sex-specific quartiles.
A number of factors were assessed via questionnaire at
baseline and preceding examinations. Smoking status was
assessed at baseline as current cigarette smoker (smoked
regularly in the past year), former smoker, or never smoked.
Caffeine use, incorporating coffee and tea intake, was de-
fined as the sum of daily coffee intake (1 cup equals 1
caffeine unit) and daily tea intake (1 cup equals 0.5 caffeine
units). Caffeine units were grouped into 0 –2 caffeine units
consumed per day or more than 2 caffeine units per day
based on previous work.(23–26) Current weekly intake of
beer, wine, or hard liquor was grouped into current user or
HANNAN ET AL.
nonuser of alcohol, as well as grams of alcohol consumed
per week.(27) We also evaluated alcohol in categories based
on a previous cross-sectional study by our group that
showed an association with BMD: ,1.0 oz/week, 1 to ,3.0
oz, 3.0 to ,7.0 oz, and 7.0 oz/week or more.(28) For women,
current use of oral conjugated estrogen, patch, or cream at
baseline was examined for its possible effect on bone loss
over the follow-up, based on our prior work.(29) Physical
activity at baseline was examined using two different as-
pects. First, we evaluated sex-specific quartiles of the Fra-
mingham 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.(30,31) The Framingham physical activity score has been
used in cardiovascular research to predict heart disease
outcome.(32,33) Second, we defined two baseline inactivity
variables: first, those subjects who responded affirmatively
to “spending most of the day in bed or a chair,” and second,
whether the participant reported spending most of the day
indoors. We also inquired about general health status using
the question “In general, how is your health now?” and
categorized respondents into two groups of excellent or
good versus fair or poor.
Serum 25-OH vitamin D concentration was determined
by a competitive protein-binding assay.(34) Inter- and intra-
assay CVs for the 25-OH D assay were 10% and 7%,
respectively.(35) Baseline serum levels of (25-OH) vitamin
D were available on 715 of the longitudinal subjects and
evaluated by categories of low (4 to ,20 ng/ml), medium
(20 –30 ng/ml), and high (.30 ng/ml) based on prior
work.(36) Baseline dietary calcium intake, including calcium
supplements, was collected from 671 of the subjects based
on the Willett 126-item food frequency questionnaire and
evaluated by categories of low (145– 400 mg/day), moder-
ate (.400 – 800 mg/day), and high (.800 mg/day) levels of
calcium.(37,38)
Data analysis
We examined percent change from baseline BMD to the
4-year follow-up BMD as well as absolute change in bone
density. Analyses were conducted separately for men and
women. Percent change in BMD was calculated as the
difference between baseline and follow-up BMD, divided
by baseline BMD, and multiplied by 100. We assessed these
components in 5-year age groups by sex. Baseline charac-
teristics were compared using Student’s t-tests or x2-tests as
appropriate. We evaluated each BMD site separately, using
multiple linear regression to examine the relation of BMD
percent change with risk factors. Multivariate regression
analyses were conducted with simultaneous adjustment for
all variables, except calcium intake and serum vitamin D
because they were assessed on only a subset of subjects.
Models were adjusted further for calcium intake and serum
vitamin D for the 671 subjects with these data, controlling
for all other risk factors as well. To examine the possibility
of nonlinear associations, we analyzed quartiles of certain
risk factors (weight, height, physical activity, calcium, and
vitamin D). Where possible, adjusted mean BMDs (least
squared means 6 SE) are presented for the categories of
RISK FACTORS FOR LONGITUDINAL BONE LOSS IN ELDERS 713

TABLE 1. COMPARISON OF FRAMINGHAM COHORT MEMBERS ATTENDING BOTH BASELINE AND FOLLOW-UP EXAMINATIONS
TO THOSE MEMBERS ONLY ATTENDING BASELINE EXAMINATION

Attended Attended only

both exams baseline exam
(n 5 800) (n 5 341) P-value

Mean baseline age (years 6 SD) 74.5 6 4.5 77.8 6 5.8 0.0001
(range) (67–90) (67–95)
Mean baseline weight (lbs 6 SD) 155.7 6 32.2 151.7 6 29.3 0.0846
(range) (87–327) (89–270)
Percent female 63.2% 57.4% 0.0640
Mean baseline BMD (g/cm2 6 SD):
Radial shaft 0.592 6 0.135 0.580 6 0.142 0.1796
Femoral neck 0.788 6 0.144 0.757 6 0.150 0.0015
Trochanter 0.707 6 0.160 0.691 6 0.176 0.1830
Ward’s area 0.603 6 0.146 0.584 6 0.163 0.0714
Lumbar spine 1.168 6 0.234 1.182 6 0.256 0.4390
Ultradistal radius 0.288 6 0.087 0.290 6 0.086 0.8080
Percent current smoker 9.4% 12.5% 0.2620
Former smoker 45.7% 45.5%
Never smoker 44.9% 42.0%
Mean alcohol at baseline (oz/week 6 SD) 2.3 6 3.7 2.3 6 4.0 0.7345
Mean physical activity score (6SD) 33.7 6 5.6 32.0 6 5.2 0.0001
(range) (24.0–63.2) (24.0–51.7)
Calcium intake (mg/day 6 SD) 810.53 6 437.34 783.59 6 415.96 0.4080
Serum 25-OH vitamin D (ng/ml 6 SD) 30.3 6 12.3 28.8 6 12.8 0.0682
Women only
Percent current estrogen use 6.7% 2.1% 0.0210
Ever used estrogen 38.8% 30.8% 0.0470

Number for attendees is based on BMD for either femur or radius scan.

risk factors. Least squared means are adjusted for the risk
factors, that is, they are the means that would be expected
for each category if subjects had the same mean values on
confounders. No adjustments were made to P-values for
multiple comparisons. All analyses were conducted using
the SAS statistical analysis package (SAS Institute Inc.,
Cary, NC, U.S.A.; version 6.12). Similar results were found
whether the outcome was the absolute change in BMD or
the percent change. We present percent change analyses
because they are somewhat easier to interpret and perhaps
more intuitive.
RESULTS
Of the 1132 subjects who had baseline radius BMD
assessed, 764 cohort members (486 women and 278 men) or
67% had valid, repeat BMD measures as part of their
regular clinic visit in 1992–1993. From the 1102 baseline
femur scans, 741 subjects had valid, longitudinal scans
(67%). From the longitudinal subset with callback BMDs
available, 567 cohort members had longitudinal spine scans
and 557 members had longitudinal wrist scans. The mean
age at baseline (examination 20) for those subjects with
longitudinal data was 74 years 6 4.5 years, with an age
range of 67–90 years. Table 1 compares the 800 cohort
members with valid longitudinal femur and/or radial shaft
data to those 341 members who only attended the baseline
examination and did not obtain follow-up. Nearly half of the
nonparticipants died during the follow-up period (43%), 89
(25%) were examined at home or in a nursing home where
we were unable to perform BMD scans because of lack of
machine mobility, and 110 cohort members failed to attend
the follow-up examination. The cohort members without
longitudinal data were more likely to be older and male, and
their gender-specific mean baseline BMDs were lower than
those members who attended follow-up. Nonparticipants
were not as likely as participants to have reported good
health, had lower physical activity scores, and were more
likely to report inactivity at baseline examination (subject
spent most of the day in bed or in a chair or spent most of
day indoors).
The mean baseline femoral neck BMD for women was
0.732 g/cm2 with a 4-year loss of 0.026 g/cm2 (Table 2).
Average percent BMD loss across the 4 years of follow-up
for women ranged from 4.8% loss at the radial shaft (1.2%
loss per year) to 3.4% loss at the trochanter site (0.86% loss
per year). For men, the mean baseline femoral neck BMD
was higher than that of women, 0.885 g/cm2 with a 4-year
loss of 0.014 g/cm2. Average percent loss during the
follow-up for men ranged from 3.6% at the radial shaft
(0.9% loss per year) to 0.17% at the trochanter site (0.04%
loss per year). As seen in Table 2, the mean 4-year BMD
loss was much greater for women than the loss for men at
the femur sites but similar at the forearm and spine BMD
714 HANNAN ET AL.

TABLE 2. MEAN CHANGE IN BMD (6SE) OVER 4-YEAR FOLLOW-UP FOR WOMEN AND MEN
Baseline Absolute Mean percent Mean percent
BMD (g/cm2) change (g) change (6SE) loss/year

Women (n 5 486)
Femoral neck 0.732 6 0.0002 20.026 23.48 6 0.01 0.87
Trochanter 0.632 6 0.0003 20.023 23.42 6 0.02 0.86
Ward’s area 0.561 6 0.0003 20.026 24.22 6 0.02 1.06
Radial shaft 0.515 6 0.0002 20.026 24.84 6 0.02 1.21
Lumbar spine 1.072 6 0.0005 20.046 24.48 6 0.02 1.12
Ultradistal radius 0.240 6 0.0002 20.012 24.24 6 0.04 1.06
Men (n 5 278)
Femoral neck 0.885 6 0.0005 20.014 21.51 6 0.03 0.38
Trochanter 0.844 6 0.0005 20.002 20.17 6 0.03 0.04
Ward’s area 0.674 6 0.0006 20.005 20.63 6 0.04 0.16
Radial shaft 0.723 6 0.0003 20.027 23.59 6 0.02 0.90
Lumbar spine 1.328 6 0.0062 20.006 20.37 6 0.04 0.09
Ultradistal radius 0.370 6 0.0003 20.013 23.09 6 0.05 0.77

Sample size for analysis may vary by site.

FIG 1. Distribution of percent of change in BMD for FIG 2. Percent of change in femoral neck BMD for
femoral neck and radius. women and men by age group.

sites. Annualized rates of BMD loss are seen also in Ta-
ble 2.
Figure 1 presents percent change in radial shaft and
femoral neck BMD for women and men over the 4 years of
follow-up. At the femoral neck site, 41% of women lost
between 5% and 33% of their baseline BMD while 23% lost
between 1% and 4%, 10% had less than 1% change in bone
density, and 16% showed 1– 4% gain in BMD from baseline
with a further 10% showing a 5–20% gain in femoral neck
BMD. At 4-year follow-up 64% of women lost between 1%
and 24% of their baseline femoral neck BMD. Men had a
similar pattern of percent change in femoral neck BMD
although slightly more men had less than 1% change in
BMD (14%) and 27% had BMD loss between 5% and 31%.
In both sexes there was a trend for bone loss, although some
subjects gained BMD over the follow-up. The distributions
of percent change at the other BMD sites were similar to the
femoral neck site for both men and women.
Fig. 2 presents the mean percent change in femoral neck
BMD for women and men across the five-year age groups.
Both men and women in all age groups lost BMD on
average over the four years of follow-up. Percent loss in
femoral neck BMD ranged from 2.2 to 8.1 percent in
women and from 1.1 percent to 6.2 percent in men across
the age groups. Percent loss at the radial shaft BMD across
the 5 year age groups ranged from 3.9 percent to 5.5 percent
in women and from 1.0 percent to 4.9 percent in men.
Typically, the loss in BMD was similar across the baseline
age groups at each BMD site. Indeed, age considered as
either a continuous variable or in age groups was not asso-
ciated with bone loss at any skeletal site (all P-values .
0.75) for women or men.
Table 3 shows the multivariate adjusted mean percent
BMD change for women during the 4 years of follow-up for
those risk factors that were associated with bone loss at any
site in either gender at P , 0.10. After controlling for the
possible effects of other covariates, women in the lower
weight quartiles and those women losing 5% or more of
RISK FACTORS FOR LONGITUDINAL BONE LOSS IN ELDERS 715

TABLE 3. LEAST SQUARES MEAN ADJUSTED PERCENT BMD CHANGE (6SE OF LEAST SQUARED MEAN) AT FEMORAL NECK,
TROCHANTER, RADIAL SHAFT, AND LUMBAR SPINE FOR SELECTED RISK FACTORS FOR WOMEN
Risk factor n Femoral neck Trochanter Radial shaft L2–L4 spine

Weight quartile (lbs)

Q1 (91–124) 117 24.21 6 1.0\ 25.78 6 1.2\ 25.35 6 1.1 26.68 6 1.4§
Q2 (125–141) 117 23.23 6 0.9§ 24.92 6 1.2\ 25.58 6 1.1* 24.51 6 1.4†
Q3 (142–158) 117 21.81 6 1.0† 22.68 6 1.2† 25.36 6 1.1 21.34 6 1.5
Q4 (159–327) referent 117 20.04 6 1.1 20.13 6 1.3 23.93 6 1.2 21.73 6 1.6
Weight change
5% Loss 114 24.25 6 1.0‡ 28.20 6 1.2\ 25.85 6 1.1 25.52 6 1.4†
No change (referent) 286 22.36 6 0.8 23.10 6 1.0 25.62 6 0.9 23.01 6 1.2
5% Gain 68 20.74 6 1.1* 11.01 6 1.4§ 23.71 6 1.2* 22.20 6 1.7
Alcohol intake
0 to ,1 oz (referent) 232 22.39 6 0.8 20.92 6 1.0 24.21 6 0.9 23.74 6 1.2
1–3 oz 163 22.05 6 0.9 21.54 6 1.1 25.53 6 1.0* 22.05 6 1.3*
.3–7 oz 37 22.28 6 1.4 24.65 6 1.7† 26.18 6 1.5 23.24 6 1.9
.7 oz 36 23.09 6 1.4 26.61 6 1.7§ 24.31 6 1.5 25.28 6 2.2
Cigarettes
Never (referent) 243 22.12 6 0.9 24.39 6 1.1 24.80 6 0.9 23.33 6 1.3
Former 176 22.68 6 0.9 23.39 6 1.1 23.53 6 0.9* 24.71 6 1.2
Current 49 22.56 6 1.2 22.51 6 1.5 26.85 6 1.3 22.69 6 1.9
Current estrogen
No (referent) 432 23.74 6 0.6 24.52 6 0.7 25.38 6 0.6 24.86 6 0.8
Yes 32 21.16 6 1.4† 22.33 6 1.7 24.77 6 1.5 22.30 6 2.0

Models adjusted for age, weight, weight change, height, alcohol intake, current estrogen use, and smoking status; sample size for
analysis may vary by site.
* 0.05 , P , 0.10 or borderline.
†
P , 0.05.
‡
P , 0.01.
§
P , 0.001.
\
P , 0.0001.

their baseline weight had significantly more bone loss (Fig.
3A). As seen in Fig. 3A, women who gained 5% or more of
their baseline weight lost less bone or had slight gains in
BMD compared with women with less than a 5% change
from their baseline weight. Weight considered as a contin-
uous variable was associated with bone loss at all skeletal
sites (e.g., for the femoral neck, the b-coefficient is 0.043
with a P value of 0.0009). Women who had baseline alcohol
intakes of over 3 oz and over 7 oz had greater bone loss at
the trochanter site than those women who had minimal
alcohol intake (0 to ,1 oz) (Table 3). Similar results were
found only at the trochanter site when alcohol was consid-
ered as a continuous variable. Current estrogen replacement
use appeared to be associated with less BMD loss in
women, especially at the femoral neck site where women
not using estrogen replacement lost nearly 3% more BMD
over follow-up (Fig. 4) than women using estrogen. Sur-
prisingly, caffeine use, physical activity, serum 25-OH
vitamin D levels, or calcium intake did not affect bone
loss. There were no differences in bone loss between
women who were inactive, compared with “active”
women using either of the surrogate inactivity measures
of spending most of the day in bed or in a chair or most
of the day indoors or between those women reporting
good health compared with those women reporting fair or
poor health. Results for Ward’s area BMD and ultradistal
radius BMD (not shown) were similar to BMDs dis-
played in tables.
For men the multivariate adjusted mean percent BMD
change across the 4 years of follow-up is shown in Table 4.
Men also showed more bone loss in the lower weight
quartiles compared with the highest weight quartile and in
those men losing 5% or more of their baseline weight
compared with men whose weight remained stable across
follow-up, although these findings were only statistically
significant at the trochanter site (Fig. 3B). Men who were
current smokers lost more BMD at the trochanter site than
men who never smoked (24% change compared 10.7%
change in BMD; P 5 0.02). At the ultradistal radius site,
men who reported poor health had greater bone loss than
men reporting good health (P 5 0.01), although no differ-
ences were seen at the other skeletal sites between men who
reported good health compared with those men reporting
poor health. Men who reported spending most of the day in
bed or in a chair had greater bone loss compared with active
men at the femoral neck (25.79% compared with 22.23%,
P 5 0.0064) and at the trochanter (23.77% compared with
11.33%, P 5 0.0028). However, those men reporting that
they spent most of the day indoors had less bone loss
compared with active men, but this was true only at the
femoral neck site (22.68% compared with 25.34% BMD
change; P 5 0.0123) and not statistically different at the
716
FIG 3. (A) Percent of adjusted mean BMD change by
weight change group for women. (B) Percent of adjusted
mean BMD change by weight change group for men.
other BMD sites for men. In men, bone loss also was not
affected by caffeine use, physical activity, serum 25-OH
vitamin D levels, or calcium intake.
DISCUSSION
This study presents longitudinal changes in BMDs at the
femur, radial shaft, lumbar spine, and ultradistal radius in a
population-based study of elderly men and women. Annu-
alized mean bone loss percentages for women ranged from
0.86% to 1.12%, while for men they ranged from 0.04% to
0.90%. During the 4-year follow-up, age-specific mean per-
cent loss in BMD among the skeletal sites ranged from 3%
to 5% in women and was somewhat less in men (0.1– 4%)
across the age groups. Mean percent loss in BMD for
women was much greater than the loss for men at all sites.
Even given the higher baseline BMD in men, the absolute
decline in BMD was greater for women than men. Elderly
men continue to lose BMD at all ages but their BMDs
remain higher than women’s BMDs and their rates of loss at
most sites were lower. Thus, our longitudinal results support
continued BMD loss through the elderly years in both men
and women.
To our knowledge, this study is the first to report vari-
ability in the distributions of bone loss (Fig. 1) in addition
HANNAN ET AL.
FIG 4. Percent of adjusted mean BMD change for women
currently using estrogen-replacement therapy and not using
estrogen-replacement therapy.
to mean bone loss. The substantial proportion of elderly
women and men experiencing bone loss of 5–33% may
offer future opportunity for prevention, while the smaller
group with 5–20% gain in bone across the 4-year follow-up
may suggest another area for future attention. We attempted
to minimize technical errors in that all scans were reviewed
and log book entries on patient positioning problems also
were reviewed, such that no technical errors could be found
with the study scans included in our analyses. These percent
differences in bone represent values beyond the CV, indi-
cating losses beyond possible technical measurement error.
Nevertheless, because only two measures were used to
create the percent change variable, there is a higher variance
than if more than two measures were used and a greater
likelihood of measurement error. It is possible that the
extremes of BMD change would be minimized by having
more measures on a subject (e.g., three measures across
time or average of two measures at each exam); however,
additional measurements are not available for these sub-
jects. Future studies with larger numbers of subjects who
lose or gain large amounts of BMD may offer opportunities
to understand the factors that explain the extremes of bone
changes and may elucidate the underlying pathophysiology
and permit targeting of interventions for important subsets
of individuals.
The bone loss rates at the femoral neck in our study are
similar to those reported by Jones et al. in the Dubbo study
and by Ensrud et al. for women at the femoral neck.(11,12)
The Rotterdam study with 2-year femoral neck bone loss for
elderly subjects also found a higher bone loss in women
compared with bone loss in men.(18) However, their annu-
alized femoral neck bone loss for women was slightly less
than our study (20.6% per year compared with 20.9% per
year) and for men it was similar to our findings of 20.4%
per year.
The age-specific baseline BMD levels reported in this
paper for men and women are approximately 20% higher
that those reported by Looker et. al using the National
Health and Nutrition Examination Survey III data, although
their age groupings were 60 – 69 years, 70 –79 years, and
RISK FACTORS FOR LONGITUDINAL BONE LOSS IN ELDERS 717

TABLE 4. LEAST SQUARED MEAN ADJUSTED PERCENT BMD CHANGE (6SE OF LEAST SQUARED MEAN) AT FEMORAL NECK,
TROCHANTER, RADIAL SHAFT, AND LUMBAR SPINE FOR SELECTED RISK FACTORS, FOR MEN
Risk factor n Femoral neck Trochanter Radial shaft L2–L4 spine

Weight quartile (lbs)

Q1 (118–155) 68 24.38 6 1.0* 24.99 6 1.3\ 23.13 6 0.9 27.67 6 1.1§
Q2 (156–172) 68 22.87 6 1.1 21.94 6 1.4‡ 23.96 6 0.9 25.60 6 1.1†
Q3 (173–193) 68 21.74 6 1.1 10.91 6 1.4 23.55 6 1.0 22.23 6 1.2
Q4 (194–294) referent 69 21.93 6 1.1 12.31 6 1.5 22.37 6 1.0 22.79 6 1.2
Weight change
5% Loss 59 24.34 6 1.0† 24.43 6 1.3† 23.43 6 0.9 26.73 6 1.1†
No change (referent) 185 22.19 6 0.7 21.10 6 0.9 23.68 6 0.7 24.17 6 0.9
5% Gain 29 21.85 6 1.4 12.62 6 1.8† 22.30 6 1.2 23.43 6 1.4
Alcohol intake
0 to ,1 oz (referent) 94 22.68 6 0.9 22.19 6 1.2 21.92 6 0.8 24.87 6 0.8
1–3 oz 83 22.66 6 1.0 20.13 6 1.2 22.12 6 0.9 23.28 6 0.9
.3–7 oz 43 22.57 6 1.3 20.68 6 1.6 23.70 6 1.1 24.46 6 1.7
.7 oz 53 23.27 6 1.1 20.87 6 1.4 24.79 6 1.0† 26.61 6 2.0
Cigarettes
Never (referent) 91 21.77 6 0.9 10.56 6 1.1 23.91 6 0.8 24.48 6 1.0
Former 161 21.19 6 0.7 10.91 6 0.9 23.55 6 0.6 25.87 6 0.9
Current 21 25.42 6 1.6† 24.37 6 2.1† 21.94 6 1.5 23.99 6 1.6
General health
Good (referent) 237 23.26 6 0.8 22.28 6 1.0 22.65 6 0.7 25.98 6 1.0
Poor 32 24.76 6 1.5 20.16 6 2.0 24.66 6 1.3 24.89 6 1.7
Most of day in bed/chair
No (referent) 209 22.23 6 0.9 11.33 6 1.2 23.86 6 0.9 24.76 6 1.1
Yes 45 25.79 6 1.4‡ 23.77 6 1.8‡ 23.44 6 1.2 26.10 6 1.5

Models adjusted for age, weight, weight change, height, alcohol intake, and smoking status; sample size for analysis may vary by site.
* 0.05 , P , 0.10 or borderline.
†
P , 0.05.
‡
P , 0.01.
§
P , 0.001.
\
P , 0.0001.

801 years and included only the femur site.(39) Addition-
ally, the NHANES data were collected using a Hologic
scanner (Hologic, Inc., Waltham, MA, U.S.A.), which may
explain some of the apparent discrepancy between our study
and Looker’s study.(40) Age-specific bone loss rates for
women are similar to those reported for these older age
groups at the radius by Ensrud et al. and for both women
and men at the femoral neck as reported by Jones et al.(11,12)
Burger et al. saw bone loss in the Rotterdam study up to age
80 years but no increased rate after age 80 years.(18) We
continued to see bone loss in subjects 81– 85 years old and
86 –90 years old in our study, as did Ensrud et al. in the
Study of Osteoporotic Fractures cohort of women.(11)
This study reports bone loss at the femur, radial shaft,
lumbar spine, and ultradistal radius sites, whereas the other
longitudinal studies have focused solely on the femoral neck
or radial shaft site. Indeed, few studies have attempted to
measure BMD at multiple sites in their subjects. Previous
work from the 1980s suggests that among elderly persons,
BMD of the ultradistal radius site may remain relatively
stable with age whereas bone densities of other sites, espe-
cially the calcaneous and femur, may show substantial
losses in elderly persons with age.(41– 43) We saw bone loss
at all sites for both sexes with age. Nevertheless, our results
also show a lack of concordance between skeletal sites and
the risk factors we studied, possibly because of increased
variability at some sites, notably the spine and ultradistal
radius sites.
The lumbar spine is well known for presenting difficulties
in measurement of elderly persons due to aortic calcifica-
tions, osteophytes, and other degenerative changes; yet we
included our results for this site.(44 – 47) Despite the probable
contributions to spinal BMD by these artifacts in elderly
persons, we found bone loss in lumbar spine BMD for both
men and women. The ultradistal radius site also presents
difficulty in evaluating longitudinal change. This site often
is difficult to measure precisely because of differences in
positioning and errors with bone edge detection caused by
low bone mass. Similar to our results, other studies have
reported little age-related ultradistal radius bone loss in the
elderly, and it is likely that there is minimal measurable
bone loss in the ultradistal site, especially given the impre-
cision of this site.(48,49)
Body mass index, physical activity, alcohol, and calcium
intake have been shown to affect BMD level.(27,28,50 –56) The
strongest relation in our study was the link between higher
weight and less bone loss as well as the ability to maintain
bone in those subjects with a 5% or greater gain in weight
718
over the follow-up period. These results confirm findings
from our cross-sectional study that reported that high body
weight appeared to protect against low BMD.(50) Further,
although in women weight loss had similar effects on bone
loss at weight-bearing sites (femur) and nonweight-bearing
sites (radius), weight gain appeared to have stronger asso-
ciations with slowing bone loss at weight-bearing sites.
Thus, a loading effect may be implicated as a possible
mechanism to maintain bone in the elderly but it is not
overwhelmingly clear. Nevertheless, these findings for
weight and weight loss highlight the importance of weight
on bone health.
We attempted to evaluate surrogate measures of inactivity
and found no effect of these factors on change in BMD. Our
measures of physical inactivity did not indicate a strong
relation with 4-year bone loss; however, these surrogate
measures may not sufficiently capture elderly activities and
may have insufficient variation in activity across the study
groups. Better measures of physical activity that are appro-
priate to an elderly age group may produce different results.
We found that women whose current alcohol consump-
tion was 7 oz (207 ml) a week or more had greater bone loss
at the trochanter than women in the lightest category of
intake (less than 1 oz per week). This association was not
seen at other BMD sites in women. In men, alcohol con-
sumption at this level was not associated with bone loss
compared with the lowest intake. Although other studies
have suggested that moderate alcohol intake in women may
result in higher BMDs, we did not find this in our study
examining current alcohol intake.(55,57,58) In our previous
cross-sectional study of Framingham participants we found
that women with alcohol intake of 7 oz or more had higher
BMDs; however alcohol intake was averaged for typical use
over a 20-year period.(28) Other cross-sectional epidemio-
logical studies have found little effect of alcohol intake on
bone.(52,59) A longitudinal study by Hansen et al. in post-
menopausal women comparing women who drank at least
once a week with nondrinkers reported that the drinkers had
lower rates of bone loss than nondrinkers.(57) Similarly,
Burger et al. report a lower bone loss rate with increasing
alcohol intake in men.(18) Our 4-year longitudinal results for
alcohol may imply that short-term bone loss may occur in
women drinking 7 oz or more of alcohol per week; however,
our previous cross-sectional findings imply a positive cu-
mulative effect of alcohol on bone for women. We were
unable to confirm a protective effect of alcohol on bone loss
in elderly women or men.
Our study found that men who were current smokers lost
more BMD at the trochanter site than men who never
smoked, but we did not observe any differences between
female smokers and nonsmokers. Our previous cross-
sectional study in the Framingham population also found
cigarette smoking to be a strong risk factor for low BMD in
men but not in women.(25) Burger showed higher bone loss
in elderly males as well as in females who smoked com-
pared with nonsmokers in the Rotterdam study.(18) The
effect of smoking on bone loss in the men of our study,
along with similar findings from the Rotterdam study and
other cross-sectional studies, provides another rationale for
smoking cessation, even among elderly persons.(18,25,60,61)
HANNAN ET AL.
We found that women who currently used estrogen re-
placement tended to have less bone loss. A protective effect
of estrogen replacement therapy on bone loss was not ob-
served at all BMD sites; however, the lack of consistency
may be a result of the low numbers of women (n 5 32) who
were current estrogen users in our longitudinal study. A
protective effect of estrogen and serum estrogen levels on
BMD have been reported in cross-sectional and longitudinal
studies.(62,63) Prior studies of the Framingham cohort de-
scribed lower BMD in women not using estrogen replace-
ment therapy, compared with users.(29,64) The Study of
Osteoporotic Fractures reported that current estrogen users
had 33% lower rates of bone loss than nonusers, similar to
the effects in our study, although the only statistically sig-
nificant difference in our study was at the trochanter site.(11)
Surprisingly, 4-year bone loss in our study was not af-
fected by caffeine, physical activity, serum 25-OH vitamin
D, or calcium intake. Many epidemiological studies of
calcium intake and BMD in elders do not show a large, if
any, impact on bone health, implying that other risk factors
may be of greater importance in this age group.(65,66) Lack
of association may be a result of influences of other com-
peting risk factors with larger effects on bone than these
factors in our study or may relate to a relatively low fre-
quency of exposure decreasing the statistical power to de-
tect an association. Intermittent rather than continuous ex-
posure also is possible for these factors. Further, these
factors may only have effects over the long term rather than
the 4-year bone loss evaluated in our study.
This study had several limitations. First, we had only two
points in time to examine the longitudinal aspect of BMD
loss in the cohort. Ideally, several points of BMD evaluation
over time would have been preferred to stabilize the pattern
of change in BMD. Second, cohort members who were
unable to come to the clinic building did not participate in
the BMD portion of the Framingham examinations because
the Lunar densitometer was not mobile. Nonambulatory
institutionalized elderly, often a frail group, were not in-
cluded in our study, and they may have lower BMDs. Third,
different technology assessed femoral and spine BMDs at
baseline and at follow-up examinations, although femoral
site data were “standardized” using published correction
factors. Finally, there are very few nonwhite subjects in the
Framingham sample, and our results are not generalizable to
this group.
In conclusion, BMDs at the femur, radius, lumbar spine,
and ultradistal radius continue to fall with age in elderly
women and men in this population-based cohort. Elderly
men continue to lose BMD at all ages but their BMDs
remain higher than women’s BMDs and their rates of loss
are lower. Data were presented for each sex by 5-year age
groups, thus providing information on men as well as the
very elderly. Risk factors consistently associated with bone
loss in elders include female sex, thinness, and weight loss
of 5% or more, whereas gaining weight (5% or more)
appears to protect against bone loss in both men and
women. This population-based study suggests that current
estrogen use may help to maintain bone in elderly women,
while current smoking adversely affects BMD in men. To
have an impact on bone loss and elderly fracture rates, risk
RISK FACTORS FOR LONGITUDINAL BONE LOSS IN ELDERS
factors of interest need to be potentially modifiable and of
sufficient prevalence in the population, such that instituting
a change may prevent bone loss at the population level.
Even in the elderly years, potentially modifiable risk factors,
such as weight, estrogen use, and cigarette smoking, exist
that are important components of bone health.
ACKNOWLEDGMENTS
We are grateful to the Framingham cohort participants
and staff and also thank the densitometer technicians Mimi
Brodsky, Mary Hogan, and Cherlyn Mercier. Components
of this work were presented in part as concurrent sessions at
the 16th and 17th Annual Scientific Meetings of the
ASBMR in Kansas City, MO, U.S.A. and in Seattle, WA,
U.S.A. as well as the Association of Rheumatology Health
Professionals 32nd Annual Scientific meeting in Washing-
ton, D.C., U.S.A. This work was supported in part by the
National Institutes of Health (NIH) grant RO1-AR/AG
41398, NIH grant RO1-AR20613, and by NIH/NHLBI con-
tract N01–38038.
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Address reprint requests to:
Marian T. Hannan
Hebrew Rehabilitation Center for Aged
Research and Training Institute
1200 Centre Street
Boston, MA 02131-1097, U.S.A.
Received May 28, 1999; in revised form December 7, 1999;
accepted December 8, 1999.