Evaluation du métabolisme osseux et minéral - arl · Evaluation du métabolisme osseux et minéral René Rizzoli Service des maladies osseuses ... Calcium homeostasis The regulation

Evaluation du métabolismeEvaluation du métabolismeosseux et minéralosseux et minéral

René RizzoliRené Rizzoli

Service des maladies osseusesService des maladies osseuses[Centre collaborateur de l[Centre collaborateur de l’’OMS pour la prévention deOMS pour la prévention de

ll’’ostéoporose]ostéoporose]Département de réhabilitation et gériatrieDépartement de réhabilitation et gériatrie

Hôpitaux universitaires et Faculté de médecine de GenèveHôpitaux universitaires et Faculté de médecine de Genève

Lausanne, 13 mars 2008Lausanne, 13 mars 2008

Mme W. 74 ansMme W. 74 ans

Fatigue, Fatigue, Pouteau-CollesPouteau-Colles, pas d, pas d’’autre fractureautre fracture

Taille 163 (- 3 cm)Taille 163 (- 3 cm)

Pas dPas d’’autre plainte, sinon un épisode deautre plainte, sinon un épisode decolique néphrétique à lcolique néphrétique à l’’âge de 68 ansâge de 68 ans




Pas dPas d’’autre plainte, sinon un épisode de coliqueautre plainte, sinon un épisode de coliquenéphrétique à lnéphrétique à l’’âge de 68 ansâge de 68 ans

FSC normaleFSC normaleCalcium Calcium 2.60 (2.20-2.60)2.60 (2.20-2.60)PhosphatePhosphate 0.82 (0.80-1-35)0.82 (0.80-1-35)CréatinineCréatinine 9090

CalciumCalcium

BoneBone Extraskeletal Extraskeletal

• Skeletal rigidity (hydroxyapatite)• Calcium store

• Skeletal rigidity (hydroxyapatite)• Calcium store

Calcium:Calcium: its role its role

• Enzymes• Muscles• Nerves• Secretion• Cell signalling

• Enzymes• Muscles• Nerves• Secretion• Cell signalling

Calcium homeostasis

The regulation of calcium homeostasis is aimed at maintaining

extracellular ionized calcium concentration as constant as possible, in a very narrow range.

The regulation of calcium homeostasis is aimed at maintaining

extracellular ionized calcium concentration as constant as possible, in a very narrow range.

Calcium in the bodyCalcium in the body

Cells: Cells: Cells: 10 g10 g

Extracellular fluid: ExtracellularExtracellular fluid: fluid: 1 g1 g

Bone and teeth: Bone and teeth: Bone and teeth: 1200 g1200 g

Circulating calciumCirculating calcium

Total calcium: 2.4 Total calcium: 2.4 mmol/lmmol/l

Protein-bound mostly albumin

40%

Protein-bound mostly albumin

1.0 mmol/l 40%

Complexed (citrate,

bicarbonate, phosphate,etc)

10%

Complexed (citrate,

bicarbonate, phosphate,etc)

10%Ionized

50%

Ionized 1.2 mmol/l

50%

Protein-Corrected Protein-Corrected Plasma Calcium (mM)Plasma Calcium (mM)

= Ca / [= Ca / [prot/160 prot/160 + 0.55]+ 0.55]

Albumine-Corrected Albumine-Corrected Plasma Calcium (mM)Plasma Calcium (mM)

= Ca= Ca + [0.02 x (40-Albumine)]+ [0.02 x (40-Albumine)]





FSC normaleFSC normaleCalcium Calcium 2.60 (2.20-2.60)2.60 (2.20-2.60) (albumine 36 -> Ca 2.68) (albumine 36 -> Ca 2.68)PhosphatePhosphate 0.82 (0.80-1-35)0.82 (0.80-1-35)CréatinineCréatinine 9090

Daily calcium fluxes controllingDaily calcium fluxes controlling calcium homeostasiscalcium homeostasis

Diet 1000 mg

Diet 1000 mg

Faeces 800 mgFaeces 800 mg

Absorption 400 mg

Absorption 400 mg

Loss 200 mgLoss

200 mg

Filtered 10000 mgFiltered 10000 mg

Reabsorbed 9800 mg

Reabsorbed 9800 mg

CellsCells

fluid

Extracellular fluid

Urinary excretion: 200 mgUrinary excretion: 200 mg

Accretion 300 mg

Accretion 300 mg

Resorption 300 mg

Resorption 300 mg

Daily calcium fluxes controllingDaily calcium fluxes controlling calcium homeostasiscalcium homeostasis

Diet 1000 mg

Diet 1000 mg

Faeces 800 mgFaeces 800 mg

Absorption 400 mg

Absorption 400 mg

Loss 200 mgLoss

200 mg

Filtered 10000 mgFiltered 10000 mg

Reabsorbed 9800 mg

Reabsorbed 9800 mg

CellsCells

fluid

Extracellular fluid

Urinary excretion: 200 mgUrinary excretion: 200 mg

Accretion 300 mg

Accretion 300 mg

Resorption 300 mg

Resorption 300 mg

CalcitriolCalcitriol

CalcitriolCalcitriol

++

++

PTHPTH++

PTHPTH++

PTHPTH++

• Skeleton

• Skeleton

Phosphate in the bodyPhosphate in the body

: structural constituent (hydroxyapatite)

• Cells• Cells- cell metabolism and energy regulator - signal transduction

- cell metabolism and energy regulator - signal transduction

Total body store = 800 gTotal body store = 800 g

• ECF• ECF - acid–base homeostasis - acid–base homeostasis

85% 15%

Daily Phosphate Fluxes ControlingPhosphate Homeostasis (mg / day)

Absorption(950)

Secretion (150)

Accretion(250)

Resorption(250)

Soft Tissues

Extracellular fluid

Diet (1200)

Faeces (400)

Filtered load(4'300)

Reabsorption(3'600)

Urine (800)

Absorption(950)

Secretion (150)

Accretion(250)

Resorption(250)

Soft Tissues

Extracellular fluid

Diet (1200)

Faeces (400)

Filtered load(4'300)

Reabsorption(3'600)

Urine (800)

PTHHigh Ca++

PTHCalcitriol

PTHCalcitriol

IGF-1Low Pi diet

+ +

+

+-

Insulin+

Daily Phosphate Fluxes ControlingPhosphate Homeostasis (mg / day)

Evaluation of Evaluation of calcium-phosphate metabolismcalcium-phosphate metabolism

ExampleExample::

••VariableVariable Plasma CalciumPlasma Calcium

••MechanismMechanism Intestinal AbsorptionIntestinal AbsorptionBone Bone TurnoverTurnoverRenal Tubular ReabsorptionRenal Tubular Reabsorption

••ControlerControler PTHPTHCalcitriolCalcitriolOther Other Hormones Hormones and and cytokinescytokines

Intestinal Calcium AbsorptionIntestinal Calcium Absorption

Calbindin Calbindin D 9kD 9k (Vit. D +++) (Vit. D +++)

LumenLumen ECFECF

Ca-ATPaseCa-ATPase(Vit. D ++)(Vit. D ++)

ChannelsChannels(Vit D ±)(Vit D ±)

CaCa++++Rate-Rate-Limiting StepLimiting Step::

== Transcellular Transcellular

��= ��= ParacellularParacellular

Absorption Absorption Depends Depends on:on:-- Chemical Form Chemical Form- pH- pH-- Sojourn Sojourn Time Time

Intestinal Calcium Absorption:Intestinal Calcium Absorption: Methods Methods of of MeasurementMeasurement

1. 1. Metabolic Metabolic BalanceBalance ((with nonabsorbable with nonabsorbable marker)marker)Net Absorption = Net Absorption = Dietary Intake Dietary Intake - - Fecal ExcretionFecal Excretion

2. Absorption of 2. Absorption of IsotopicIsotopic Minerals Minerals (Single or Double, Radioactive or Stable)(Single or Double, Radioactive or Stable)

3. Segmental Intestinal Absorption 3. Segmental Intestinal Absorption (Segmental (Segmental PerfusionPerfusion))

4. Indirect 4. Indirect AssessmentAssessment- - Urinary Urinary Calcium Calcium Excretion Excretion Before and AfterBefore and After an Acute an Acute Oral CalciumOral Calcium LoadLoad ((PakPak ’’s Test)s Test)- - 24-Hour24-Hour Urinary Urinary Calcium Calcium ExcretionExcretion

Calcium Absorption Test Calcium Absorption Test (Pak(Pak’’s Test)s Test)

TimeTime (min) 0(min) 0 120120 240240 360360UrineUrine CollectCollect CollectCollect

BreakfastBreakfast with with1000 mg Calcium1000 mg Calcium

DiscardDiscardMictionMiction

Calcium/Calcium/CreatinineCreatinine

(Phosphate,cAMP)(Phosphate,cAMP)

DosageDosage Calcium/Calcium/CreatinineCreatinine

(Phosphate,cAMP)(Phosphate,cAMP)

SerumSerum((optionaloptional))Calcium,Phosphate,Calcium,Phosphate,

CreatinineCreatinine,PTH,PTHCalcium,Phosphate,Calcium,Phosphate,

CreatinineCreatinine,PTH,PTH

n:n: Increase Increase Calcium/ Calcium/CreatinineCreatinine < 0.5 < 0.5

Evaluation of Main CalciumEvaluation of Main Calcium FluxesFluxes

Fasting Urinary Calcium/CreatinineFasting Urinary Calcium/Creatinine ( > 0.5( > 0.5 mmol/mmol mmol/mmol))

-> -> NetNet Bone Resorption Bone Resorption

24 h24 h Urinary Urinary CalciumCalcium Excretion Excretion ( > 7.5( > 7.5 mmol/d mmol/d inin Men Men,, > 6.25> 6.25 mmol/d mmol/d inin Women Women))

->-> Net Intestinal Calcium AbsorptionNet Intestinal Calcium Absorption((and/or and/or NetNet Bone Resorption Bone Resorption))

UrinaryUrinary Pi > 32 Pi > 32 mmol mmol/d /d -> -> Dairy Products OriginDairy Products OriginUrinaryUrinary Sodium > 200 Sodium > 200 mmol mmol/d /d -> -> HighHigh Salt Salt Intake Origin Intake Origin


ExampleExample::




Bone RemodelingBone Remodeling

1.1. Maintenance of Maintenance of Mechanical StrengthMechanical Strength(Replacement of (Replacement of Fatigued BoneFatigued Bone, , Prevention Prevention of Excessive of Excessive AgingAging))

2.2. Supply Supply of of Bone Marrow with Growth FactorsBone Marrow with Growth Factors

3.3. Mineral Homeostasis Mineral Homeostasis (Calcium Release)(Calcium Release)

Manolagas et al., NEJM, 1995

Sex Sex HormoneHormoneDeficiencyDeficiency

->->Increased Increased

RemodellingRemodelling

Remodelling cycle in adult human bone

Remodelling completed

Remodelling completed

Resting stageResting stage

Resorption 20 days

Resorption 20 days

Formation 150 daysFormation 150 days

Reversal phaseReversal phase

~200 days~200 days

B.Ar.

B.Pm.

1,2,3..

Ct.Ar.

Ct.Wi

Vd.Ar.

T.Ar.

N.Bf.

PRIMARYMEASUREMENTS

DERIVEDPARAMETERS

BV/TV, Tb.Th., Th.N.N.Bf./B.Ar., Por,....

1

2

3

Morphometry Morphometry on iliac creston iliac creststructural parametersstructural parameters

INDICATIONS TO TRANSILIAC BONE BIOPSY

••Suspected OsteomalaciaSuspected Osteomalacia

••Characterization Characterization of of Renal OsteodystrophyRenal Osteodystrophy

••Suspected Hereditary Bone DiseaseSuspected Hereditary Bone Disease

••Osteoporosis Osteoporosis in Youngin Young Individuals Individuals

Adapted from Eriksen et al. 1994

•82 µm•2.6 min•< 5µSvhrpQCT hrpQCT ->->

«« Virtual Virtual Bone BiopsyBone Biopsy »»

Biochemical markers of bone turnoverBiochemical markers of bone turnover

Formation markersFormation markers

•• S-OsteocalcinS-Osteocalcin

•• S-Bone specific alkaline S-Bone specific alkaline phosphatasephosphatase

•• S-Procollagen S-Procollagen type-1 type-1

N-propeptideN-propeptide

•• S-Procollagen S-Procollagen type-1 type-1

C-propeptideC-propeptide

Resorption markersResorption markers

•• UU--HydroxyprolineHydroxyproline

•• U-Hydroxylysine U-Hydroxylysine

•• U-Pyridinoline U-Pyridinoline

•• U- U-DeoxypyridinolineDeoxypyridinoline

•• S-Bone sialoprotein S-Bone sialoprotein

•• S-Acid S-Acid phosphatasephosphatase

•• S-Tartrate-resistant S-Tartrate-resistant acidacidphosphatasephosphatase

•• S-/U-Type-1 S-/U-Type-1 collagen collagen telopeptides telopeptides (CTX, NTX)(CTX, NTX)

Potential Uses of Markers of Potential Uses of Markers of Bone RemodelingBone Remodeling

-Identify patients who need treatment-Identify patients who need treatment•• Correlate with bone lossCorrelate with bone loss•• Correlate with fracture riskCorrelate with fracture risk

-Help in selecting therapeutic agent-Help in selecting therapeutic agent

-Early indicator of response to treatment-Early indicator of response to treatment

-Evaluate patients who are not responding to-Evaluate patients who are not responding toconventional treatmentconventional treatment

11

22

33

44

55

Odds-ratioOdds-ratio

LowLow hiphipBMDBMD

highhighU-CTXU-CTX

LowLow BMDBMD++

highhigh CTXCTX

Garnero Garnero et et alal., 1996., 1996

Hip Fracture Hip Fracture RiskRisk

Variability and TemporalPatterns of Change

Delmas P., 2000

1- 2 yrs. 3 -6 months

Bone Mineral Density Bone TurnoverΔ Δ

Precision Error0 0

Collagen

Type I Type I collagen epitopes and Cathepsin collagen epitopes and Cathepsin K K cleavage cleavage sitessites

NN CC

a2 (I) JYDGKGVGa2 (I) JYDGKGVG GPP-SAGFDFSFLPQPPQ EKAHDGGR a 1GPP-SAGFDFSFLPQPPQ EKAHDGGR a 1

NTXNTX CTXCTXICTPICTP

CKCK CKCK CKCK CKCK

CKCK CKCK

GarneroGarnero et et al al., JBC, 1998., JBC, 1998

Sassi Sassi etet al al., ., BoneBone, 2000, 2000

DeoxypyridinolineDeoxypyridinolinePyridinolinesPyridinolines

---- ALN / Placebo ALN / Placebo

---- ALN / ALNALN / ALN (Pooled 5 mg and 10 mg groups)(Pooled 5 mg and 10 mg groups)

7070

6060

5050

4040

3030

2020

1010F 0F 0 F 1F 1 F 2F 2 F 3F 3 F 4F 4 FL 0FL 0 FL 1FL 1 FL 2FL 2 FL 3FL 3 FL 4FL 4 FL 5FL 5

YearYear

NTX

(N

TX ( p

mol

/pm

ol/ µµ

mol

cre

atin

ine

mol

cre

atin

ine ))

Start of FLEXStart of FLEX

F = FIT, FL = FLEXF = FIT, FL = FLEX

Pre

-P

re-

men

opau

sal

men

opau

sal

Ran

geR

ange

Mean Percent ChangeMean Percent Change

––1515––5555151525253535

00 1212 2424 3636 4848 6060

25%25%

Black et al., Black et al., JAMA 2006JAMA 2006

Mean Urinary NTXfrom Start of FIT Through FLEX (Per Protocol)

Different Effects Different Effects of of Bisphosphonates andBisphosphonates andEstrogen Therapy Estrogen Therapy onon Free Free and Peptide-Boundand Peptide-Bound

Bone Bone Cross-linksCross-links Excretion Excretion((Garnero Garnero etet al., J.al., J. Bone Bone Min. Res. 10:641-649,1995)Min. Res. 10:641-649,1995)

Cross-links:Cross-links: TotalTotal Peptide-BoundPeptide-Bound FreeFree

BisphosphonatesBisphosphonates DecrDecr.. Decr Decr.. No changeNo change

EstrogenEstrogen DecrDecr.. Decr Decr.. DecrDecr..

PlaceboPlaceboPTH 20PTH 20PTH 40PTH 40

Bone-SpecificBone-SpecificAlkaline Alkaline PhosphatasePhosphatase

UrineUrineN-telopeptideN-telopeptide

--220000

2200440066008800

110000112200114400

00 66 1122 1188 2244

% C

hang

e (

% C

hang

e ( ±±

SE)

SE)

PlaceboPTH 20PTH 40

00110000220000330000440000550000

00 66 1122 1188 2244MMoonntthhss

11 33

Med

ian

% C

hang

e (

Med

ian

% C

hang

e ( ±±

SE)

SE)

Neer Neer et al 2001et al 2001

Effects hPTHEffects hPTH(1-34) on (1-34) on bone bone TurnoverTurnover

Biochemical Markers of BoneTurnover

• Pre-analytical Conditions-Sample Storage-Diurnal Variation-Food Intake

• Individual Variation

• Assay Variation & Performance

• Renal Function

Influenced by:

Time (Hours)17 20 23 2 5 8 11 14 17

DPy

d/C

erat

-20-15-10-505

10152025

PreMPEarly MPLate MP

Mean / SEM

A.Schlemmer et al. J Bone Miner Res 1994;9:1883

MyeloidMyeloidProgenitorProgenitor

OsteoclastOsteoclastPrecursorPrecursor

Active Active OsteoclastOsteoclast

OsteoblastOsteoblast / / Stromal CellStromal Cell

RANKLRANKL OPGOPGRANKRANK

TRAILTRAIL

OPGOPG =Osteoprotegerin=OsteoprotegerinRANKLRANKL = RANK Ligand= RANK LigandRANKRANK =Receptor Activator =Receptor Activator of of Nuclear Factor-kBNuclear Factor-kBTRAILTRAIL = = TNF-related Apoptosis-Inducing TNF-related Apoptosis-Inducing LigandLigand






TRAILTRAIL






TRAILTRAIL

CSF-1CSF-1

TGFßTGFßEstrogenEstrogen

1,25D1,25DPGE2PGE2PTHPTHIL-11IL-11


ExampleExample::


••MechanismMechanism Intestinal AbsorptionIntestinal AbsorptionBone ResorptionBone ResorptionRenal Tubular ReabsorptionRenal Tubular Reabsorption


Renal calcium handlingRenal calcium handling

200 mg

200 mg /day

8%8%

Loop diureticsLoop diuretics

Filtered 10000 mg/day

Filtered 10000 mg/day

65%65%

++ –––

25%25%

ECF: extracellular fluidECF: extracellular fluid

• Acidosis – • Pi depletion – • Acidosis – • Pi depletion –

•• PTH PTH ++ •• PTHrP PTHrP +

•• Alkalosis Alkalosis ++ •• Thiazides Thiazides ++

ECFcontraction/expansion

Plasma CalciumPlasma Calcium Plasma PhosphatePlasma Phosphate

U Ca U Ca ExcretionExcretion U Pi U Pi ExcretionExcretion

TmPi TmPi / GFR/ GFRTRCaITRCaI

Renal Tubular Reabsorption of Renal Tubular Reabsorption of Calcium or PhosphateCalcium or Phosphate

Plasma CalciumPlasma Calcium Plasma PhosphatePlasma Phosphate

U Ca U Ca ExcretionExcretion U Pi U Pi ExcretionExcretion

TmPi TmPi / GFR/ GFRTRCaITRCaI

Renal Tubular Reabsorption of Renal Tubular Reabsorption of Calcium or PhosphateCalcium or Phosphate

PTHPTH PTHPTH

0.350.35

0.300.30

0.250.25

0.200.20

0.150.15

0.050.05

0.000.00

0.100.10

1.41.4 1.31.3 1.21.2 1.11.1 1.01.0 0.90.9 0.80.8 0.70.7 0.60.6 0.50.5 0.40.4

U/P

Ca

/ U/P

U

/P C

a / U

/P c

reat

inin

ecr

eatin

ine

TRCa I / plasma CaTRCa I / plasma Ca

Tubular Reabsorption Tubular Reabsorption of Calcium Indexof Calcium Index

Ca-Ca-CreatCreat. in plasma . in plasma and and urine -> FECa -> urine -> FECa -> Nomogram Nomogram -> TRCaI-> TRCaI

0.0

1.0

2.0

3.0

4.0

5.0 2.0

1.6

1.2

0.8

0.4

0.0

1.8

1.4

1.0

0.6

0.2

2.0

1.6

1.2

0.8

0.4

0.0

1.8

1.4

1.0

0.6

0.0

1.0

2.0

3.0

4.0

5.0

0.99

0.95

0.90

0.800.70

0.60

0.50

0.40

0.30

0.20

0.10

0.01

0.05

0.10

0.20

0. 30

0. 40

0. 50

0. 60

0. 70

0. 80

0. 90

1.00

TRP

Fractional excretion

Plas

ma

PiRenal threshold Pi (Tm

Pi/GFR)


ExampleExample::








FSC normaleFSC normaleCalcium Calcium 2.60 (2.20-2.60) (albumine 36 -> Ca 2.68)2.60 (2.20-2.60) (albumine 36 -> Ca 2.68)PhosphatePhosphate 0.82 (0.80-1-35)0.82 (0.80-1-35)CréatinineCréatinine 9090PTHPTH 9.5 (1.0-6.5)9.5 (1.0-6.5)

Secretion of parathyroid hormoneSecretion of parathyroid hormone

PTH PTH Ca++Ca++PTHPTH

Parathyroid cellParathyroid cell

Ca++Ca++

PTH (1PTH (1––84)84)

Calcium sensorCalcium sensor

848411

Ca++Ca++

synthesis and secretion synthesis and secretion

Human Parathyroid Hormone 1-34 and 1-84

1 10

20

30

Ser Val Ser Glu Ile Gln Leu Met His AsnLeuGly

LysHisLeuAsnSerMetGluArgValGluTrpLeu

Arg Lys Lys Leu Gln Asp Val His Asn Phe

50

40

6070

80

-COOH

H2N-

841

Parathyroid Parathyroid hormonehormone

EpitopeEpitope::

••N-terminalN-terminal

••C-terminalC-terminal

••Mid-Mid-moleculemolecule

••IntactIntact

••Intact «Intact «bioactivebioactive»»

HalfHalf--LifeLife::

Cleavage Cleavage Site: 33-34 + 36-37Site: 33-34 + 36-37in Liver in Liver and Kidneyand Kidney

< 4 < 4 minmin

>90>90 min min

4 4 minmin

7-7-

2-2-

PTHPTH

Plasma CalciumPlasma Calcium

7.07.0

1.01.0

2.252.25 2.60 2.60

°°°° °°

°°°°

°°11

22 33

44

5566

BioactiveBioactive IntactIntact

JCEMJCEM 90:6370-2,200590:6370-2,2005

Magnesium deficiencyMagnesium deficiency

Magnesium deficiencyMagnesium deficiency

PTH secretion and/or actionPTH secretion and/or actionPTH secretion and/or action

HypocalcemiaHypocalcemiaHypocalcemia

Parathyroid hormone/parathyroidParathyroid hormone/parathyroid hormone-related proteinhormone-related protein

11 11 8484

141141

PTH (9.6 kD)PTH (9.6 kD)

PTH-PTH-rPrP (16 (16 kDkD))homology: 62%homology: 62%

1212

11 1313Chromosome

PTHPTH

Tubular reabsorption

Tubular reabsorption

Pi Pi Absorption Absorption

FormationFormation

ResorptionResorption

1,25(OH)2 D31,25(OH)2 D3

Ca -Ca -

Parathyroid gland TumorTumorPTH-rPPTH-rP

Effects of parathyroid hormone-relatedEffects of parathyroid hormone-related protein in malignancyprotein in malignancy

Ca - Ca - PiPi

cAMPcAMP

HypercalcemiaHypercalcemia++

Low Low PTHPTH++

High cyclic High cyclic AMPAMP

==PTHrPPTHrP

Vitamin D metabolism

UV lightUV light Vitamin D (cholecalciferol)Vitamin D

(cholecalciferol)Diet

• PTH • Hypocalcemia • Hypophosphatemia • IGF-1

• PTH • Hypocalcemia • Hypophosphatemia • IGF-1

25OHD3 25OHD3

Target organsTarget organsTarget organs

1,25(OH)2D3 1,25(OH)2D3

++

Skin 80%80%20%20%

Circulating forms of vitamin DCirculating forms of vitamin D

Half-lifeHalf-life

1 – 5 nmol/l

1 – 5 nmol/l 20 – 100 nmol/l* 50 – 150 pmol/l

Circulating levels

Circulating levels

4 – 5 days 10 – 20 days 5 – 18 hours

4 – 5 days 10 – 20 days

• Vitamin D

• 1,25(OH)2D3

• Vitamin D • 25OH D

3

*Reflects vitamin D supply and status*Reflects vitamin D supply and status

(1991)(1991)

20022002idid

IdId

T-ScoreT-Score< - 2.5< - 2.5

IdIdIdId

idid

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Evaluation du métabolisme osseux et minéral - arl · Evaluation du métabolisme osseux et minéral René Rizzoli Service des maladies osseuses ... Calcium homeostasis The regulation