McKayla Edgren

Professor Nixon
Epidemiology
May 2, 2014

Calcium Intake and Osteoporosis
Public Health Significance:
Bone health within the skeletal system is a very important part of the wellbeing of the
entire body. Bones are responsible for the structure of the body as well as protecting vital
organs, providing muscle attachments for movement, and storing important minerals that
are vital for functioning (CDC
1
)
Osteoporosis, which means porous bones, is a disease of the bones that is caused by
a loss of mass or density (CDC
1
). It causes the bones to become more porous and
susceptible to injury and fractures. With osteoporosis, bones may not be able to rebuild
and replace themselves like they would normally (NOF
2
)
About 52 million Americans are affected by osteoporosis and low bone mineral
density (NOF
2
). Studies show that one out of every two women will be affected by
osteoporosis due to a fracture, as well as every one out of four men (NOF
2
). An
estimated 30% of postmenopausal women already have osteoporosis in the United States
(IOF
3
).
There are many consequences of low bone mineral density, osteoporosis, and bone
fractures. Breaking a bone may have serious complications especially in older adult
populations. Those that are over 50 years of age would have a more difficult time
recovering from a fracture and it makes a major impact on quality of life and daily
activities (NOF
2
). Most of the time fractures are observed in the spine, hip, or wrist in
patients with osteoporosis, but they may occur in other areas or bones (NOF
2
). These
fractures may cause severe pain, a change in posture, and height. Many times, patients
that have had a fracture to the vertebrae will develop a permanent stoop or hunch. Since
patients with fractures may develop a disability and lack the capacity to perform their day
to day activities, occupations, and pastimes they may also foster feelings of depression
and separation (NOF
2
). Many elderly patients that experience a fracture require extra
care and nursing. Excess mortality is also a possible outcome. One statistic estimates
that 20 percent of elderly patients that break a hip will die within a year of the incident
due to complications from treatment or healing (NOF
2
).
Along with the obvious physical and psychological burdens of osteoporosis, there is
also a large financial burden. In the United States alone, osteoporosis is accountable for
19 billion dollars in costs along with 2 million bone fractures (NOF
2
). Some experts
estimate that the numbers will rise to 25.3 billion dollars and approximately 3 million
fractures within the next 10 years (NOF
2
).
In an effort to prevent osteoporosis and low bone mineral density, the relationship of
calcium consumption and osteoporosis is being analyzed. Calcium is a mineral that is
found in the body and it is only absorbed through diet and consumption (NIH
4
). The
body is not able to synthesize calcium so it must be obtained from food or supplements.
Calcium plays a major role in the building of bone and bone density as well as other
functions in the body (NIH
4
). It is also responsible for carrying out tasks within the heart,
muscular, and nervous system (NIH
4
).
In the United States, calcium consumption is recommended differently for populations
based on age and gender (NIH
4
). Older adults, women, and adolescents need greater
amounts of calcium in their daily diets due to: the inevitable decline in bone health due to
aging; the loss of hormones after menopause, which affects bone reabsorption; and
growth and development periods in children (NIH
4
)
Biologic Plausibility:
The biologic plausibility between the exposure of calcium and the outcome of
osteoporosis is dependent on the relationship of calcium and bone health. Calcium is a
major component in the remodeling process of bones (NIH
4
). When the body does not
have enough calcium to maintain the functionality of the heart and muscles then it
removes calcium stored in the bones. This allows the bones to become weak and porous
which will lead to low bone density, osteoporosis, and ultimately, bone fractures (CDC
1
).
Literature Review:
Most of the literature available for the relationship between calcium consumption as
an exposure and osteoporosis as the outcome is conclusive that calcium is important in
building healthy bones and its presence may reduce the risk for osteoporosis and bone
fractures. Several of the articles were based solely on populations of older adults,
specifically postmenopausal women who are at an increased risk for osteoporosis and
fractures.
Two of the studies found that a large percentage of adults do not meet their daily
recommended amount of calcium. Only about 32% of adults between the ages of 50 and
70 met their recommendation of 1,000 mg of calcium per day. In the nurses cohort study
only 36% met their daily recommendation for adequate calcium intake.
Calcium supplement use ranged from 1.5% in women aged 16-18 to 46.4% in women
over the age of 70. Several of the studies mentioned and looked at the difference between
dietary calcium and calcium from supplements. Part of the nurses cohort study found
that 27% of total daily calcium consumption is derived from supplements alone.
Throughout the study the self-reported use of supplements increased. Total calcium
intake including diet and supplements was found to have an association with a reduced
risk of hip fracture when comparing populations that consumed greater than 1,200
mg/day and populations that consumed less than 600 mg/day. The relative risk for hip
fracture was 0.90 (95% CI: 0.67, 1.21).
Other studies that researched bone mineral densities in comparison to calcium intake
also found a positive relationship. The Womens Health Initiative and observational
study found that greater calcium consumption led to a higher hip and total bone mineral
density in postmenopausal women between the ages of 50 and 79. The group that was
given a calcium supplement of 1,000 mg/day had a significant difference in BMD when
compared to the placebo group (P<0.01). The combined CT and OS studies found a
relative risk of 0.65 (95% CI: 0.44, 0.98; P=0.02). There was no significant difference,
however, in reduced risk for fractures.
The retrospective study of postmenopausal women found that those in the lowest
quartile group of calcium intake had an odds ratio of developing osteoporosis that was
1.46 times that of women that were in the highest quartile of calcium consumption
(95%CI: 1.12,1.89; P=0.008). The lowest quartile included those who had less than 7
weekly portions of calcium or less than 300 mg/day. The highest quartile included
women with greater than 16 weekly portions of calcium or about 686 mg/day.
There are also several limitations to these studies. Several of the studies measure
dietary calcium intake through questionnaires so there is a possibility of recall error and
bias. Another limitation is the measurement of supplement use. The Womens Health
Initiative study was criticized for including women who were already taking supplements
in some of their data. A couple of the studies only lasted a couple of years. The short
time period could have been an issue when looking for the development of osteoporosis.
Public Health Recommendation:
Based on these journal articles my public health recommendation for calcium
consumption would be different depending on age and gender of the specific population.
Since osteoporosis develops mostly in older adults these studies focused mainly on adults
and postmenopausal women between the ages of 50 and 70 and older than 70.
For postmenopausal women there is a reduced risk of developing osteoporosis and
low bone mineral density if a daily calcium intake ranges above 1,500 mg. There is a
10% reduction in risk of hip fracture if consumption is above 1,200 mg per day.
Therefore, post-menopausal women above the age of 50 should consume between 1,200
and 1,500 mg per day of calcium.
For older men there is no reduction in risk of developing osteoporosis and loss of bone
mineral density if consumption of calcium is between 1,100 and 1,500 mg per day. Men
above the age of 50 should intake 1,100 to 1,500 mg of calcium per day. Although there
is no significant difference in reduction of risk, a lower intake of calcium could increase
the risk for osteoporosis and low bone mineral density.


Calcium Intakes and Femoral and Lumbar Bone Density of Elderly U.S. Men and Women: National Health and Nutrition Examination
Survey2005-2006 Analysis
Design,
Population, and
Investigator
Definition of
exposure variable
Definition of
outcome measures

Sample
Characteristics
Calcium Intake
measurement
Osteoporosis
outcome
measurement
Main findings Dose-response Adjustments
2005-2006
observational
cross-sectional

Subjects were
elderly residents
statistically
representative of
the US from the
National Health
and Nutrition
Examination
Survey

(Anderson et al,
2006
5
)
2,214 participants
>50 years old

213 participants
were excluded for
unreliable dietary
recall or no valid
bone scan or
missing BMI

Final sample for
femoral BMD:
1,556 total
participants
843 men
713 women

Final sample for
spinal BMD:
1384 total
participants
715 men
Calcium
consumption was
measured as the
sum of their dietary
intake and their
consumption via
supplements and
antacids.

2 24-hour recalls
were administered
by NHANES (one
in person and
another over the
telephone).

If a participant had
2 reliable recalls
then they were
averaged, if there
was only one
reliable recall it was
Proximal femurs and
lumbar spines were
scanned using dual-
energy x-ray
absorptiometry.
Large percentages
of older adults do
not achieve their
daily RDA of
calcium through
only diet.
Only 9-17% is at or
above the RDA in
the groups besides
the males ages 50-
70.
With diet and
supplements the
calcium intake is
better for many
older Americans.
More of them were
able to reach their
RDA.
(32% of males
71+yo;
41% of males
The effects were in
different directions
within different
age groups and
gender.

For males 50-70
and females 50-70
there were no
significant
differences in
femoral density
among the
quintiles of
calcium intake.

For males and
females 71+ total
calcium quintile
was a significant
predictor of
femoral neck
BMI, total
calorie
intake,
dietary
protein,
serum
vitamin D,
PTH, and
estimated
glomerular
filtration rate
Age, sex,


669 women only used.

Information on
supplements was
obtained during
each participants
home visit by
NHANES.

Quintiles of calcium
intake were
computed within
subgroups of the
study.

Group is largely
white
5070 yo; and
females 71+yo)
density after
controlling for
BMI (P=0.02, P=
0.04).
Calcium, Vitamin D, Milk Consumption, and Hip Fractures: A Prospective Study among Postmenopausal Women
Design,
Population, and
Investigator
Definition of
exposure variable
Definition of
outcome measures

Sample
Characteristics
Calcium Intake
measurement
Osteoporosis
outcome
measurement
Main findings Dose-response Adjustments
18 year
prospective
study
1980-1998
Postmenopausal
women
American
Journal of
Clinical
Nutrition
Nurses Health
Study (NHS)
cohort

(Feskanich et al,
2003
6
)
1980: Began with
27,532
postmenopausal
women that
responded to an
initial dietary
questionnaire and
had not reported a
previous hip
fracture, cancer,
heart disease,
stroke, or
osteoporosis.
72,337
postmenopausal
women in 18 years
until 1998.
Assessment of diet
through semi
quantitative food-
frequency
questionnaire (FFQ)
which included self-
report/recall of the
previous year.
Included dairy
foods and
supplements or
nutrient intakes.
Data from US
Department of
Agriculture sources
and food
manufacturers
research.
Doses of calcium
per day were
stratified into:
<400 mg
400-900 mg
Participants reported
all previous hip
fractures at baseline
and incident
fractures were
reported biennially.
Cases only included
fractures of proximal
femur that were
caused by low or
moderate trauma.
Self-report except
for validation study
in which 30 reported
fractures were all
confirmed by
medical records.
603 fractures were
identified.
10% of women
(7,466) reported
diagnosis of
osteoporosis.
Calcium
supplements
contributed 27% of
total intake.
Only 36% of NHS
women had an
adequate calcium
intake.
Higher total
calcium intake from
food plus
supplements was
associated with a
lower-risk of hip
fracture in the
simple age-adjusted
analysis.
No, higher calcium
intake was not
associated with
reduced risk for
hip fracture.
Age, calcium
supplement
use.


901-1300 mg
>1300 mg
RR for hip fracture
was 0.90 (95% CI:
0.67, 1.21; P=0.34)
in women
consuming >1200
mg/d of calcium
when compared to
those consuming
<600.
A dietary calcium
intake of >900
mg/d was not
associated with any
reduction in
fracture risk.
RR=1.33; 95% CI:
0.79, 2.23; P=0.67).
Health Risks and Benefits from calcium and Vitamin D supplementation: Womens Health Initiative Clinical Trial and Cohort Study
Design,
Population, and
Investigator
Definition of
exposure variable
Definition of
outcome measures

Sample
Characteristics
Calcium Intake
measurement
Osteoporosis
outcome
measurement
Main findings Dose-response Adjustments
Average 7 year
intervention
double-blind,
placebo-
controlled
clinical trial.
Companion
prospective
observational
study.

Womens Health
Initiative (WHI)

(Prentice et al,
2013
7
)
36,282
postmenopausal
women in the U.S.
50-79 yo
randomized at 40
clinical sites.
1994-1999

93,676
postmenopausal
women.
50-79 yo
1994-1998

Exclusions:
5,145 baseline
history of breast
cancer
15,511 no
mammogram
within 2 years prior
to OS enrollment
1,108 daily
Calcium was
measured through a
food frequency
questionnaire
(FFQ).
Dietary
supplements were
obtained in clinic
visits.
There was also an
interviewer-
administered four-
page form that was
used to collect
information on
single vitamin and
mineral
supplements and on
multivitamin/multi-
mineral usage
(frequency or pills
per week and
duration such as
The clinical
outcomes that the
study focused on
were hazard ratios of
hip fracture, and
total fracture
depending on
calcium and vitamin
D.
A significantly
higher hip and total
body bone mineral
density was found
in the trial group
versus the placebo
(P<0.01).

No evidence for hip
or total fracture risk
reduction.

In women not
taking supplements
at baseline, the
hazard ratio for hip
fracture in the
control-trial after 5
or more years of
calcium and
vitamin D
supplementation
versus the placebo

Yes, there was a
response in
increasing BMD
for an increase in
calcium
consumption.
Age, BMI,
adherence to
supplement


corticosteroid users
5,675 urinary tract
stones at baseline

Final OS sample:
68,719

months or years).

Stratified by
percentiles:
5
th
: 57mg/d
10
th
143mg/d
25
th
200mg/d
50
th
571mg/d
75
th
1,000mg/d
90
th
1,305mg/d
95
th
1,640mg/d

OS
125mg/d
171mg/d
400mg/d
400mg/d
400mg/d
600mg/d
800mg/d


was 0.62 (95% CI:
0.38, 1.00).

Combined CT and
OS:
Hazard Ratio was
0.65 (95% CI: 0.44,
0.98; P=0.02).

There was little or
no association for
supplementation for
the total fracture.
Effects of dietary calcium intake on body weight and prevalence of osteoporosis in early postmenopausal women
Design,
Population, and
Investigator
Definition of
exposure variable
Definition of
outcome measures

Sample
Characteristics
Calcium Intake
measurement
Osteoporosis
outcome
measurement
Main findings Dose-response Adjustments
1998-2004 Cross-
sectional,
retrospective,
observational.

(Varenna et al,
2007
8
)
1,771 women
within 5 years of
spontaneous
menopause

excluded at
baseline: those
with early
menopause
(before the age of
45)

191 women
excluded who
had diseases or
who were taking
drugs that
influenced
weight and
calcium
metabolism.
Calcium
consumption was
measured by a
weekly food-
frequency
questionnaire.

Categorized:
weekly servings and
portion sizes into
quartiles (<7, 8-11,
12-15, and >16).

1 portion=300mgCa
Height, weight and
BMI calculations.

BMD was calculated
at lumbar level by
dual-energy X-ray
absorptiometry

Osteopenia and
osteoporosis were
defined by WHO
criteria (BMD<0.909
and 0.759g/cm2).
Women belonging
to the lowest
quartile of calcium
intake showed a
significantly greater
risk of having
osteoporosis than
did subjects in the
highest quartile
when using the
overweight
variable. P<0.0001

Women in the
lowest quartile had
an OR of having
osteoporosis that
was 1.46 times that
in women in the
highest quartile of
calcium intake.
OR=1.46
95%CI: 1.12,1.89
P=0.008

Yes: Quartile 4<
Quartile 3
<Quartile 2
<Quartile 1 for
osteoporosis
Age, BMI,
lifestyle habits,
caffeine,
smoking,
alcohol, SES,
reproductive
variables,
medical
history, drug
use
Longitudinal Changes in Calcium and Vitamin D Intakes and Relationship to Bone Mineral Density in a Prospective Population-
Based Study: the Canadian Multicentre Osteoporosis Study (CaMos)
Design,
Population, and
Investigator
Definition of
exposure variable
Definition of
outcome measures

Sample
Characteristics
Calcium Intake
measurement
Osteoporosis
outcome
measurement
Main findings Dose-response Adjustments
10 and 2 year
Prospective
population-based
study of
Canadians
1995-1997 (adult
cohort)
2004-2006
(youth cohort)
Canadian
Multicentre
Osteoporosis
Study

(Zhou 2013
9
)
Adult cohort: 9423
women and men
aged >25 living
within km of 1 of 9
study centers:
(Vancouver,
Calgary,
Saskatoon,
Hamilton, Toronto,
Kingston, Quebec
City, Halifax, and
St. Johns.
Youth cohort:
1001women and
men aged 16-24
Both cohorts were
randomly selected
by a list of
residential
telephone listings.
1 participant was
randomly selected
using a sex and age
Calcium intake was
measured through
interviewer-
administered
abbreviated semi-
quantitative food
frequency
questionnaire.
It was completed at
baseline, and year 2
for the youth cohort
and at baseline, year
5, and year 10 for
the adult cohort.
The questionnaire
asked how often,
on average, have
you eaten the
following items
during the last 12
months?
It included foods
with large amounts
Bone mineral density
was measured at the
lumbar spine,
femoral neck, and
total hip by
densitometers

At baseline,
prevalence of
supplement use was
found to range from
1.5% for 16-18 year
old women to
46.4% for women
over the age of 70.
The prevalence was
higher in women
versus men.
4% of youths were
found with calcium
consumption levels
above the upper
limit.
(95%CI: 3%, 5%)
6% (95%CI 6%,
7%) of adult
women and 4%
(95%CI 3%, 5%) of
adult men had
calcium intakes
No Age
stratified design.
Final Sample:
6518 women > 25
2864 men > 25
=9382 total (adult
cohort)
526 women 16-
24yo
473 men 16-24yo
Total=999

Year 10 follow-up
(adult cohort):
3999 women and
1570 men

Year 2 follow-up
(youth cohort):
395 women and
347 men

of calcium and food
models were
available for
assistance in
estimation of
portions.
above the UL at
baseline.
Young men: high
calcium intake
(>1500mg/day) and
high vitamin D
were associated
with higher BMD
in total hip and
femoral neck when
compared to the
reference group
which only
consumed <600
mg/day.
Adult cohort:
baseline calcium
intake of 1100-1500
mg/day was
associated with
higher baseline total
hip BMD by
0.010g/cm
2
(0.000;
0.020) in women
but with lower total
hip BMD in men by
0.023 g/cm
2
(0.004;
0.042).
In adult women
high average
calcium intake

>1500mg/day and
high vitamin D
intake were
associated with
better BMD
maintenance at all
three bone density
sites when
compared to the
reference category.
References:
1. Calcium and Bone Health. Centers for Disease Control and Prevention.
Division of Nutrition, Physical Activity, and Obesity, National Center for Chronic
Disease Prevention and Health Promotion. Ed. 6 April 2011. Accessed 1 May
2014 http://www.cdc.gov/nutrition/everyone/basics/vitamins/calcium.html.
2. What is Osteoporosis? National Osteoporosis Foundation. National
Osteoporosis Foundation. Accessed 1 May 2014 http://nof.org/articles/7.
3. Epidemiology. International Osteoporosis Foundation. International
Osteoporosis Foundation. Accessed 1 May 2014
http://www.iofbonehealth.org/epidemiology.
4. What is calcium and how does it build strong bones? National Institute of
Health. Ed. 30 November 2012. Accessed 1 May 2014
https://www.nichd.nih.gov/health/topics/bonehealth/conditioninfo/Pages/calcium.
aspx.
5. Anderson, J. J. B., K. J. Roggenkamp, and C. M. Suchindran. Calcium Intakes
and Femoral and Lumbar Bone Density of Elderly U.S. Men and Women:
National Health and Nutrition Examination Survey2005-2006 Analysis. The
Journal of Clinical Endocrinology and Metabolism.97 (12): 4531-4539.
6. Feskanich, D. W. C. Willet, and G. A. Colditz. Calcium, vitamin D, milk
consumption, and hip fractures: a prospective study among postmenopausal
women. American Journal of Clinical Nutrition. 2003; 77:504-511.
7. Prentice, R. L., M. B. Pettinger, R. D. Jackson, J. Wactawski-Wende, A. Z.
Lacroix, G. L. Anderson, R. T. Chlebowski, J. E. Manson, L. Van Horn, M. Z.
Vitolins, M. Datta, E. S. LeBlanc, J. A. Cauley, and J. E. Rossouw. Health Risks
and Benefits from calcium and Vitamin D supplementation: Womens Health
Initiative Clinical Trial and Cohort Study. Osteoporosis International. 2013 Feb;
24(2): 567-80.
8. Varenna, M., L. Binelli, S. Casari, S. Zucchi, and L. Sinigaglia. Effects of dietary
calcium intake on body weight and prevalence of osteoporosis in early
postmenopausal women. American Journal of Clinical Nutrition. 2007(86):639-
644.
9. Zhou, W., L. Langsetmo, C. Berger, S. Poliquin, N. Kreiger, S. I. Barr, S. M.
Kaiser, R. G. Josse, J. C. Trior, T. E. Towheed, T. Anastassiades, K. S. Davison,
C. S. Kovacs, D. A. Hanley, E. A. Papadimitropoulos, D. Goltzman, and CaMos
Research Group. Longitudinal Changes in Calcium and Vitamin D Intakes and
Relationship to Bone Mineral Density in a Prospective Population-Based Study:
the Canadian Multicentre Osteoporosis Study (CaMos). Journal of
Musculoskeletal Neuronal Interaction. 2013(4); 470-479.