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Osteoporosis and Nutrition
Module 4
Speaking of Bones
Osteoporosis For Health
Professionals
Susan J Whiting
University of Saskatchewan
Learning Objectives
• Understand the 3 critical nutrients for bone: calcium,
vitamin D and protein
– Recommendations for these have recently changed
• Appreciate bone is a living tissue and other nutrients
are needed
– Their impact depends on one’s baseline diet
• Intend to use dietary recommendations such as CFG
or DASH as these are bone healthy except vitamin D
– A vitamin D supplement always necessary
– These diets are low sodium, high potassium
Acknowledgments and Conflict of Interest
• This presentation is mainly based upon a slide
kit* in development through funding by
Yoplait France, and the following experts have
reviewed its content:
– Pr. Jean-Philippe Bonjour, Division of Bone Diseases, Departement of
Internal Medicine, University Hospital, Genève, Suisse
– Pr. Marius Kraenzlin, Division of Endocrinology, Diabetes, and Clinical
Nutrition, University Hospital, Bale, Suisse
– Dr. Régis Levasseur, Service de Rhumatologie et Pôle Ostéoarticulaire, CHU Angers, France
– Pr. Michelle Warren, Department of Obstetrics and Gynecology
Columbia University Medical Center, New York, USA
– Pr. Susan Whiting, College of Pharmacy and Nutrition, University of
Saskatchewan, Canada
*Updates by S. Whiting have not been vetted by the group of experts
Definition of Osteoporosis
« …a skeletal disease characterized by low bone mass
and microarchitectural deterioration of bone tissue with a
consequent increase in bone fragility and susceptibility to
fracture »
Consequences: fractures
Wrist
Spine
Hip
WHO 1994
Photos: Dempster DW et al., J Bone Miner Res 1986; 1:15. Copyright 1986 © Wiley
Pathophysiology of fragility
fracture risk in elderly
Undernutrition
+
Low level of physical activity
Bone formation
- Balance
- Muscle mass
- Neuro-muscular function
Bone resorption
Bone mass
and strength
Risk of
falls
Fracture risk
Protective
response
Importance of essential
nutrients
Calcium
Vitamin D
Protein
Vitamin D metabolism
Skin
UVB light
7-dehydrocholesterol
Vitamin D
Diet
Inactive form
Kidney
1,25(OH)2D
Active form
25(OH)D
+
1-hydroxylase
Stimulation of intestinal
calcium absorption
Circulating and
measured form
Status indicator
PTH
Hypocalcemia
Hypophosphatemia
IGF-I
25α-hydroxylase
Vitamin D metabolism
Skin
UVB light
7-dehydrocholesterol
Vitamin D
Diet
Inactive form
Kidney
1,25(OH)2D
Active form
25(OH)D
+
Circulating form
1-hydroxylase
Stimulation of intestinal
calcium absorption
Status indicator
25α-hydroxylase
1,25 is made intracellularly
Stimulation of cell growth and
differentiation in other tissues
Vitamin D metabolism
Skin
UVB light
7-dehydrocholesterol
Vitamin D
Diet
Inactive form
Kidney
1,25(OH)2D
Active form
25(OH)D
+
Circulating form
1-hydroxylase
Status indicator
Stimulation of intestinal
calcium absorption
Endocrine
pathway
25α-hydroxylase
1,25 is made intracellularly
Autocrine
pathway
Stimulation of cell growth and
differentiation in other tissues
Vitamin D deficiency in
elderly
45
25(OH)D (ng/ml)
Serum
(ng/ml)
Serul 25(OH)D
40
35
Osteoporosis Canada 75 nmol/L
30
25
IOM 50 nmol/L
20
15
10
5
Double cause of
deficiency with age:
Reduced skin
synthesis of vitamin D
Insufficient sun
exposure
0
Adults
Independent Elderly in Hip f racture
elderly
institutions
patients
Adapted from Lips P et al., Endocr Rev 2001; 22:477
Recent Meta-Analysis of Fracture
Risk: NEJM July 5, 2012
• In 11 RCTs involving
over 31,000 people, a
dose response is seen
• To achieve a
significantly reduced HR
for fracture reduction,
25(OH)D levels must be
over 60 nmol/L
Recent MetaAnalysis of
Fracture Risk:
NEJM July 5, 2012
Only when
sufficient vitamin D
is given ( > 792 IU)
to raise levels of
25(OH)D is there a
significant effect
on fracture risk.
Effect of vitamin D on the
risk of falls
Fall prevention by 1000 IU vitamin D2 supplementation
in women with a history of falling in the previous year
p<0.05
35.8 %
Percentage of subjects
40
27.2 % 27.8 %
25.2 %
30
Placebo++calcium
calciumcitrate
(1g/d)
Placebo
20
Vitamin D2 (1 000
IU)
Ergocalciferol
+ calcium
citrate
+ calcium citrate (1g/d)
10
0
First fall in
summer/autumn
First fall in
winter/spring
In 2011 the European Food Safety Authority has approved a health
claim for 800 IU of vitamin D for falls prevention in persons > 60 y
Prince RL et al., Arch Int Med 2008; 168:103
2010 Osteoporosis Canada
Recommendations for Vitamin D
Recommended intake for low-risk and younger
adults are 10-25 μg (400–1000 IU) daily
Recommended intake for high-risk and older
adults are 20–50 μg (800–2000 IU) daily
For individuals being treated for osteoporosis, vitamin D
status should be assessed by serum measurement of 25hydroxyvitamin D after 3 months of vitamin D
supplementation
To ensure levels are at or above 75 nmol/L
How to reach these
recommendations ?
3 sources of vitamin D
Diet
Sun exposure
Supplementation
Independent and cumulative effect
Foods with vitamin D
salmon
liver
sardines in oil
meat
eggs
Butter or margarine
Unlike calcium, few foods contain vitamin D in
significant amounts
Difficult to reach daily recommended intake via diet alone
Decline in previtamin D3 synthesis
in skin with age
Godar et al., Dermato-Endocrinology 3:4, 243-250; October/November/December 2011
Importance of essential
nutrients
Calcium
Vitamin D
Protein
Calcium during growth
Genetics
Spontaneous
calcium intake
Gender
Menarcheal
age
Bone
gain
Physical
activity
Other nutrients
Pubertal stage
Skeletal sites
Bonjour JP et al., Le Rhumatologue 2009; 70:19
Calcium attenuates bone
loss in women
Lumbar BMD
Mean % change ( 1 SEM)
6
3
controls
0
1000 mg Ca supplements
/ day
-3
2000 mg Ca supplements
/ day
-6
-9
Early peri
Late peri
Early post
Late post
Methodology:
248 women 46-55 y
25(OH)D levels similar
~ 18 ng/ml)
menopause
Elders P et al., J Clin Endocrinol Metab 1991; 73:533
2010 Osteoporosis Canada
Recommendations for calcium
Recommended intake for younger adults is
1000 mg daily
Recommended intake for older adults is
1200 mg daily
– New evidence suggests intake does not
need to be higher than these
recommendations
– Excess intake may lead to kidney stones
Examples of equivalence
for 300 mg of calcium
300 g of soft white cheese
1 cabbage of 850 g
1 kg of oranges
30 g of Emmental
50 g of Saint Nectaire
5 baguettes
2 yogurts
4 kg of beef
250 ml of milk
2010 Osteoporosis Canada
Recommendations for calcium
Recommended intake for younger adults is
1000 mg daily
Recommended intake for older adults is
1200 mg daily
– New evidence suggests intake does not
need to be higher than these
recommendations
– Excess intake may lead to kidney stones
Keep total intake below Upper Level of
2000 mg
Calcium and Heart Disease Risk
What is the evidence?
In the journal Heart 2012: data from ~24,000 men and
women in Germany, 35-64 y, tracked for an average of
11 years as part of a European cancer and nutrition
study.
What was reported in Abstract (underlining added):
Associations for stroke risk and CVD mortality were overall null. In
comparison with non-users of any supplements, users of calcium
supplements had a statistically significantly increased MI risk
(HR:1.86 95% CI 1.17 - 2.96), which was more pronounced for calcium
supplement only users (HR: 2.39; 95% CI 1.12-5.12)
Kuanrong Li et al. Heart 98:920-925
Calcium Supplements and Heart
Disease? What was reported:
Calcium Is a Threshold Nutrient:
More than adequate is not better
Response (c)
to increasing
intake from C
to D is almost
immeasurable
compared to
(b)
D
Supplementation is effective up to
an intake threshold
Example in prepubertal girls with high and low calcium intake
year)
peryear)
(% per
BMD (%
inBMDs
Changes
Change in
Duration: 48 weeks
6
Spontaneous calcium
intake
Spontaneous
Ca intake
Median:855
855mg/d
mg/d >
<
Median:
<
>
*
5
4
Placebo
3
Ca supplement
2
36
36
* p < 0.01
31
41
1
0
805
694 1 238
1 175 11805
54
16
56
64
Total Ca consumed (mg/d) SEM
Bonjour JP et al., J Clin Invest ; 99:1287
Importance of essential
nutrients
Calcium
Vitamin D
Protein
Protein intake reduces
fracture risk
Protein intake and hip fracture in postmenopausal women
of hip
RRRR
hip fracture
of fracture
Quartiles of total protein intake
1.2
1.0
0.8
0.6
0.4
0.2
0.0
Q1
Low
intake
Low
intake
Q2
Q3
Q4
HighHigh
intake
intake
Quartiles of total protein intakes
Munger et al., Am J Clin Nutr 1999; 69:147
Patients with recent hip fracture
Methodology:
(%) (%)
femurfemur
of proximal
in BMD
ange
of proximal
in BMD
Change
Mean age: 80.7 7.4 years
Duration:
6 months
0
Placebo and treatment: 550 mg Ca/d
0
+ 200 -1
000
IU vit D (one time)
-1
-2
p=0.029
Change in BMD of proximal femur (%)
Protein attenuates proximal
femur bone loss
p=0.029
-2
-3
-3
-4
-4
Number-5of hospital stays reduced by 21 days
0
-1
p=0.029
-2
-3
-4
-5
-6
0
6
12
-1
Proteinsupplements
supplements(20
(20 g.d )
Protein
Time (months)
+
calcium
+
vit
D
g.d-1) + calcium + vit D
Protein
supplements
(20 g.d
Protein
supplement(20
(20
g/d)-1)+ calcium + vit D
Protein
supplements
+ calcium
+ vit D
g.d-1)
+ calcium
+ vit D
Isocaloric
placebo
(calcium
+ vit D only)
Placebo
Placebo
(calcium + vit
D
(calcium + vit D only)
only)
Placebo
Placebo
(calcium + vit D
(calcium + vit D only)
only)
-5
-6
0
6
12
Schürch M et al., Ann Intern Med 1998; 128:801
Prote
Prote
(20 g
g.d-1)
+ cal
Plac
Placeb
(calc
only)
Negative consequences of insufficient
protein intake in the elderly
Functional consequences
of sarcopenia on bone
Decreased mobility
Protein balance
Anabolism
Catabolism
Increased risk of falling
Increased risk of fracture
Adapted from Rosenberg IH, Am J Clin Nutr 1989; 50:1231
Increased milk consumption improves
bone biomarkers in women
Change in bone biomarkers
(%)
10
5
0
-5
-10
***
***
***
-15
-20
PTH
***
CTX
P1NP
OC
BAP
IGF-1
***p < 0.01
Methodology:
Duration: 2 x 6 weeks
2 groups in cross-over: Ca intake  600 mg vs.1 200 mg (600 mg + ½ l of milk)
Bonjour JP et al., Brit J Nutr 2008;1
Protein Recommendations
• For bone, intake should be at least 1 g/kg
• In 2002, OC Guidelines were ““Maintain
adequate protein”
• OC is willing to accept the recommendation of
1 g/kg (compared to RDA of 0.8 g/kg)
• Protein is not the “bad” nutrient for bone
unless calcium intakes are low
No effect of diet acid-ash on
calcium balance
Change of calcium balance
(mmol/d)
Change of calcium balance
(mmol/day)
There is no relationship between a change in net acid
2
excretion and a net loss of whole body calcium.
11
Roughead 05
00
Kerstetter 06
-1
-1
Roughead 03
Dahl 95
Kerstetter 06
Kerstetter 06
Kerstetter 06
-2
-2
R² = 0.003
p = 0.38
Spence 05
-3
-3
-50
-50
-25
-25
0
0
25
25
50
50
Change
of net acid excretion (mEq/d)
Change of net acid excretion (mEq/day)
Promotion of an “alkaline diet” to prevent calcium loss is not justified
Fenton TR and al., J Bone Miner Res 2009;24:1835-1840
Vegetarian, vegan diets
and bone health
Vegetarian diets
Lacto-vegetarian diets provide sufficient calcium
and protein
Vegan diets
Vegans diets, lacking milk products or appropriate alternatives,
are low in calcium, protein, and vitamin D as well as other
nutrients important for bone growth and bone maintenance
The vegan diet requires a plant-based milk substitute or a
supplement in order to provide sufficient calcium
Protein may be limited and of poor quality unless there is an effort to
select pulses (beans), nuts, and other protein foods
Ho-Pham LT et al., Am J Clin Nutr 2009; 90:943 Janelle KC, Barr SI. J Am Diet Assoc 1995; 95:180
New SA, Osteoporos Int 2004; 15:679
There are potential benefits of
many nutrients and food
constituents
Magnesium
Phosphorus
Zinc
Manganese
Vitamin C
Vitamin K
Vitamin B12
Carotenes
Phytoestrogens
Polyphenols
Potassium
Fibre
5 nutrients have received a positive opinion
from EFSA on having evidence for a causeeffect relationship related to bone
Magnesium
Manganese*
Phosphorus*
Zinc*
Vitamin K
* EFSA ruled No current evidence for a deficiency in the population – no health claim approved
Some nutrients and food
constituents, in excess, may be
harmful to bone health
• Nutrients behave in a U-shape manner, giving rise to deficiencies when
not present in sufficient amounts and to toxicities when present in excess.
• This concept is illustrated in the following figure, where the risk of adverse
effects is zero when intakes are below the Upper level (UL).
39
When ingested in excess, these otherwise
beneficial components appear to affect bone
metabolism
Vitamin A#
Sodium*
Alcohol
# UL =3000 mcg retinol
Caffeine
* UL = 2300 mg Na
40
Some populations are at risk of deficiencies in
nutrients that may affect bone health
• Strict vegans: in addition to calcium, vitamin D and
protein – B12, zinc
• People on restrictive diet: in addition to calcium, vitamin
D and protein – B12, zinc (if restrict meat), vitamin C,
carotenes, potassium if restrict fruit & vegetables.
• Frail elderly people with low appetite: potentially low in
all bone healthy nutrients
• Those with an alcohol problem: potentially low in all
bone healthy nutrients
All of the food groups are needed to
provide all of the bone healthy nutrients
Nutrient
Fruit &
Vegetables
Calcium
√
Whole Grains
Dairy
√
Vitamin D
√
Protein
√
Vitamin K
√
Magnesium
√
√
Zinc
√
Phosphorus
√
Vitamin C
√
Carotenes
√
√
√
Manganese
B12
Meat &
Alternatives
√
√
√
√
√
Dietary pattern research: consume a bone healthy
diet
• A study of dietary patterns in Canadian men and women
over 50 y indicated that a nutrient dense diet was
protective against incident low-trauma fractures in
women:
whole grains)
*
Langsetmo et al., Am J Clin Nutr2011;93:192–9
Following the Food Guide
Ensures Bone Health
Canada’s Food
Guide ensures
adequate
calcium and
protein, and
most other
nutrients
+ recommends a
vitamin D supplement