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International Symposium
Micronutrients in Milk and Dairy Products:
New Insight and Health Benefits
Paris, May 12 2011
Calcium and Phosphate:
A Duet of Ions Playing for Bone Health
Jean-Philippe Bonjour
Division of Bone Diseases*
University Hospitals and Faculty of Medicine
Geneva, Switzerland
(* WHO Collaborating Center for Osteoporosis Prevention)
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Calcium and Phosphate:
A Duet of Ions Playing for Bone Health
Bone Trajectory Throuhout Life
Ca/Pi Ratio in Bone Compared to Dairy Products
Bone Functions and Composition
Mineralization Process: Roles of Pi and Ca
Distinct Bone Pathologic Expression of Pi vs. Ca Dietary Restriction
Interactions between Ca, Pi and Bone Cells
Ca Homeostasis: Main Fluxes & Regulators
Pi Homeostasis: Main Fluxes & Regulators
Relative importance of Ca and Pi in Osteoporosis Management
Fulfillment of Ca and Pi RDA by Foods vs. by Pharmaceutic Preparations
Distinct Extraskeletal Roles
Contribution of Dairy Foods to Ca and Pi Supply in the Population
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Bone is a dynamic
connective tissue serving
Three main functions:
- Protective against trauma
- Mechanical for locomotion
- Metabolic contributing to Ca & Pi homeostasis
Calcium and Phosphate:
A Duet of Ions Playing for Bone Health
Bone Functions and Composition
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Calcium and Phosphate:
A Duet of Ions Playing for Bone Health
Bone Functions and Composition
Cortical, Compact Bone
Trabecular, Spongious Bone
Mineral: 60%
mainly Ca-Pi
Organic Matrix: 30%
mainly proteins
Water: 10%
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Calcium and Phosphate:
A Duet of Ions Playing for Bone Health
Bone Functions and Composition
Osteoclasts
Osteoblasts
Osteocytes
Bone Cells
1-2%
4-6%
90-95%
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Calcium and Phosphate:
A Duet of Ions Playing for Bone Health
Bone Trajectory Throuhout Life
Years
Bone m
ass/S
trength
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Calcium and Phosphate:
A Duet of Ions Playing for Bone Health
Ca/Pi Ratio in Bone Compared to Dairy Products
[Ca10(PO4)6(OH)2]
70 kg Human Adult
Ca: 1300 g
P: 700g
Mass % Whole Body
99
80
Bone Crystal
Hydroxyapatite
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Calcium and Phosphate: A Duet of Ions Playing for Bone Health
MassCa/P Ratio in Bone Compared to Dairy Products
2.2
Human Milk
1.9-2.4
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Calcium and Phosphate: A Duet of Ions Playing for Bone Health
MassCa/P Ratio in Bone Compared to Dairy Products
2.2
Human Milk Cow Milk
Ewe Milk
1.9-2.4
1.3
1.3
1.3
Other Dairy Products
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Calcium and Phosphate: A Duet of Ions Playing for Bone Health
Distinct Bone Pathologic Expression of Pi vs. Ca Dietary Restriction
Pi Restriction
Osteomalacia
Ca Restriction
Osteoporosis
Bone Matrix
Bone Mineral
Normal Ca-Pi Supply
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Calcium and Phosphate: A Duet of Ions Playing for Bone Health
Distinct Bone Pathologic Expression of Pi vs. Ca Dietary Restriction
Low Phosphatemia Due to Pi Metabolism Disturbances
Mimicks Nutritional Vitamin D Deficiency in Children:
RICKETS
Fanconi and Wallgren Lehrbuch de Pädiatrie 1961 Benno Schwabe & Co ,Verlag Basel/Suttgart
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Calcium and Phosphate: A Duet of Ions Playing for Bone Health
Mineralization Process: Roles of Pi and Ca
Adapted from Caverzasio and Bonjour, Kidney Int 1996
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Calcium and Phosphate: A Duet of Ions Playing for Bone Health
Mineralization Process: Roles of Pi and Ca
Adapted from Caverzasio and Bonjour, Kidney Int 1996
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1 & 2 Preosteoblasts
3 Osteoblasts
4 & 5 Osteoblastic Osteocytes (Preosteocytes)
6, 7 & 8 Osteocytes Tamara Devel. Dyn.2006
Osteocytogénèse
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Any Role for Ca or Pi
in Osteocytogenesis ?
So what ?
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4.
Adapted from Tamara Devel. Dyn.2006 and Wang JBMR 2011
+ Pi
Control by Pi of Bone Biology
Pi Dependence of:
Osteoblast
Matrix Mineralization
And
Osteocyte Maturation
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Adapted from Zang JBMR 2011
DMP1=Dentin Matrix Protein 1
FGF23=Fibroblast Growth Factor 23
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QuickTime™ and a decompressor
are needed to see this picture.
QuickTime™ and a decompressor
are needed to see this picture.
Fukumoto. Mol Cell Endocrinol 2008
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Back to the Old Seventies
and
to Physiology and Pathophysiology
with
The Concept of a Putative
Bone-Kidney Link in Pi Homeostasis
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Is there a bone-kidney link
in the homeostasis of inorganic phosphate (Pi)?
Bonjour et al. Adv Exp Med Biol 1977; 81:319-22
Controls Mineralization
Inhibiion by EHDP
2
1
2
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Pharmacological Inhibition of Bone Mineralizatiion
Renal Pi
Reabsorption
Intestinal Ca-Pi
Absorption
FGF 23 ? 1,25-VitD
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Evidence for a physiological role of
FGF-23 in the regulation of renal
phosphate reabsorption and plasma
calcitriol in healthy humans
SL Ferrari
JP Bonjour
R Rizzoli
Division of Bone Diseases
Geneva University Hospital
Switzerland
J Clin Endocrlinol Metab 2005; 90 1519-1524
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Results: FGF-23 and diet
25
30
35
40
45
50
55
60
FGF-23 (pg/mL)
R. Low R.2 High
Diet
P=0.0004 p<0.0001
-40
-30
-20
-10
0
10
20
30
40
50
Low High
Diet
FGF-23 (%change vs R.)
Ferrari et al. J Clin Endocrlinol Metab 2005; 90 1519-1524
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FGF-23, PTH and tubular reabsorption
of phosphate (TmPi)
Normal Range
0.6
0.8
1.0
1.2
1.4
1.6
1.8
Tm
Pi
(mm
ol/L
GF
R)
0 20 40 60 80 100 120
FGF-23 (pg/mL)
R=0.28, P=0.0028
40
60
80
100
120
140
1,2
5-(
OH
)2-D
3 (
pm
ol/
L)
0 20 40 60 80 100 120
FGF-23 (pg/mL)
160
R=0.19, P=0.05
Ferrari et al. J Clin Endocrlinol Metab 2005; 90 1519-1524
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Stubbs & Quarles Semin.Dial 2007
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Tibor DENGYEL Fantastique et mythologie Les trois Parques
Greek Mythology
Life span controlled
by the 3 daughters of Zeus and Themis
Klotho who spins the thread of life.
Lachesis who determines the span of
life by measuring the length of thread.
Athropos who cuts the string
to bring a life to an end.
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Remodelling
completed
Remodeling
completed
Resting stage Resting stage
Resorption
20 days
Resorption
20 days
Formation 150 days Formation 150 days
Reversal phase Reversal phase
~200
days
~200
days
Bone Remodeling
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Remodelling
completed
Remodelling
completed
Resting stage Resting stage
Resorption
20 days
Resorption
20 days
Formation 150 days Formation 150 days
Reversal phase Reversal phase
~200
days
~200
days
Pi
Ca ?
Pi
Ca ?
Bone Remodeling
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Calcium and Phosphate: A Duet of Ions Playing for Bone Health
Interactions between Pi, Ca and Bone Cells
Marie P. Bone 46: 571-6. 2010
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Ca Homeostasis: Main Fluxes & Regulators
Pi Homeostasis: Main Fluxes & Regulators Distinct Extraskeletal Roles
Calcium Phosphate
Main Fluxes
From Rizzoli & Bonjour. Physiology of Calcium and Phosphate Homeostasis. In:
Dynamics of Bone and Cartilage Metabolism. Eds Seibel, Robins, Bilezikian. Academic Press, 2006
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Essential Role of
Renal Tubular Reabsorption
in Ca and Pi Homeostasis
But Distinct Transporters
and
Distinct Regulators
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Calcium Phosphate
Renal Handling
From Rizzoli & Bonjour. Physiology of Calcium and Phosphate Homeostasis. In:
Dynamics of Bone and Cartilage Metabolism. Eds Seibel, Robins, Bilezikian. Academic Press, 2006
Ca Homeostasis: Main Fluxes & Regulators
Pi Homeostasis: Main Fluxes & Regulators Distinct Extraskeletal Roles
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Ca Homeostasis: Main Fluxes & Regulators
Pi Homeostasis: Main Fluxes & Regulators Distinct Extraskeletal Roles
From Rizzoli & Bonjour. Physiology of Calcium and Phosphate Homeostasis. In:
Dynamics of Bone and Cartilage Metabolism. Eds Seibel, Robins, Bilezikian. Academic Press, 2006
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Calcium and Phosphate: A Duet of Ions Playing for Bone Health
Relative importance of Ca and Pi in Osteoporosis Management
Boonen JCEM 2007
Ca-Pi salt
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Relative importance of Ca and Pi in Osteoporosis Management
Treating Osteoporosis with Pi
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Calcium and Phosphate: A Duet of Ions Playing for Bone Health
Fulfillment of Ca and Pi RDA by Foods vs. by Medication Preparations
BJM 2010
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Calcium and Phosphate: A Duet of Ions Playing for Bone Health
Fulfillment of Ca and Pi RDA by Foods vs. by Medication Preparations
BJM 2010
“No association between myocardial events
in individuals who use dietary calcium in dairy and
other high calcium food to maintain adequate calcium intake.
The reasons for these differences are also unknown
but may involve a slower increase in serum calcium
in individuals receiving high calcium-containing foods
than in those using calcium supplements.”
Comments from Jo Lorenzo
Scientific Web Blog ASBMR Editor.
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Play Duet For Bone
Play Solo
For Other Vital Functions
Ca & Pi