Osteoporosis Vitamin d Deficiency Nahrain Al Zubaidi Md

7/28/2019 Osteoporosis Vitamin d Deficiency Nahrain Al Zubaidi Md

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Beyond OsteoporosisBeyond Osteoporosis

The Global Impact ofThe Global Impact ofVitamin D deficiencyVitamin D deficiency

Nahrain ALNahrain AL--Zubaidi, MD, CDE, FACEZubaidi, MD, CDE, FACE

Assistant ProfessorAssistant Professor

Endocrinology and MetabolismEndocrinology and Metabolism

Georgetown University Hospital, USAGeorgetown University Hospital, USA

Physician Nutrition SpecialistPhysician Nutrition Specialist


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Introduction


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Vitamin D Vitamin D insufficiency is an emerging global health concern.Vitamin D insufficiency is an emerging global health concern.

There is a worldwide epidemic of vitamin D deficiency inThere is a worldwide epidemic of vitamin D deficiency in

various populations, including infants, pregnant and lactatingvarious populations, including infants, pregnant and lactating

women, the elderly, individuals living in latitudes far from thewomen, the elderly, individuals living in latitudes far from the

equator, persons who avoid the sun or ultraviolet radiation inequator, persons who avoid the sun or ultraviolet radiation inthe blue spectrum (UVB),and populations with dark skinthe blue spectrum (UVB),and populations with dark skin

pigmentation.pigmentation.

Scientific evidence indicates that Vitamin D has a new andScientific evidence indicates that Vitamin D has a new and

more critical role as ubiquitous hormone at the centre of amore critical role as ubiquitous hormone at the centre of a

complex endocrine, paracrine, and autocrine system involvedcomplex endocrine, paracrine, and autocrine system involved

in maintaining general health.in maintaining general health.


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Vitamin D

Most tissues and cells in the body have a vitamin D receptor

Many studies have revealed new insights into the regulationof these receptor and new targets for its action

Several of these cells possess the enzymatic machinery toconvert the primary circulating form of vitamin D to the activeform

Vitamin D was found to play an interesting role in decreasingthe risk of many chronic illnesses, including common cancers,autoimmune diseases, infectious diseases, and cardiovasculardisease


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Vitamin D

Vitamin D is a steroid which , in its active form , has aVitamin D is a steroid which , in its active form , has a

hormone activity .hormone activity .

The major sources of vitamin D in humans areThe major sources of vitamin D in humans arecutaneous synthesis, diet, and supplementscutaneous synthesis, diet, and supplements

Vitamin D exists in two forms: D2 or ergocalciferol andD3 or cholecalciferol.

These forms differ in the side chains These differencesalter its metabolism, and overall make D2 somewhatless potent than D3.


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Vitamin D D 25-OH has a half-life in circulation of approximately 2

weeks, making it the best biomarker of vitamin D status

The conversion of vitamin D to 25OHD is under littlemetabolic control. The conversion of 25OHD to 1,25(OH)2D,however, is tightly controlled

D 25-OH is the major circulating form of vitamin D, withconcentrations in the blood approximately 1000 times that of1,25(OH)2D3. 24,25(OH)2D3 circulates at approximately 100

times that of 1,25(OH)2D3, and is therefore the second mostabundant vitamin D metabolite in blood.


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Vitamin D

Vitamin D receptor (VDR), a nuclear receptor found in mostorgans is activated by The physiologically active form ofvitamin D is 1,25-(OH)2-D

The wide tissue distribution of the VDR led to the recognitionof the noncalciotropic actions of 1,25-(OH)2-D

The calciotropic actions of 1,25-(OH)2-D include enhancementof intestinal calcium and phosphorus absorption, suppressionof parathyroid hormone secretion, and stimulation of boneresorption


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THE VITAMIN D ICEBERGTHE VITAMIN D ICEBERG

autocrine

endocrine


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THE VITAMIN D ICEBERGTHE VITAMIN D ICEBERG

cell cycle regulationgene control

Ca economy


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Cellular and tissue distribution

of vitamin D receptor

Endocrine: Parathyroid gland, thyroid, pituitary, adrenal

Central nervous system: Brain neuronsRespiratory:Alveolar cellsCardiovascular: Cardiac muscleGastrointestinal :Esophagus, stomach, hepatocytes, small

and large intestineRenal/genitourinary: Kidney, urethra, prostateReproductive :Testis, ovary, uterus, placentaMusculoskeletal : Osteoblasts, osteocytes, chondrocytes,

fibroblasts, striated muscleEpidermis : Skin, hair follicle, breastImmune :Thymus, T-cells, B-cells, macrophages


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Mechanism of action


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Vitamin Dendocrine autocrine

25(OH)D

25(OH)D

1,25(OH)2D

kidney cell

1,25(OH)2D

1--OHylase

25(OH)D

25(OH)D

1,25(OH)2D

1--OHylase

24-OHylase

varioussignalsPTH

serum PiFGF23

1,24,25(OH)3D


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AUTOCRINE ACTIONAUTOCRINE ACTION

VDR1,25D

VDR

1,25D

RXR

VDRE

Transcription


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VDRE

Transcription

cell proliferation cell differentiation

apoptosis immune response 24-hydroxylase

1515


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VDRE

Transcription

~ 800 genes

have VDREs

1616


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VDR

1,25D

VDR

1,25D

RXR

VDRE

Transcription

1,25D

25OHD 25OHD

1717


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VDR

VDR

1,25D

RXR

VDRE

Transcription

1,25D

25OHD 25OHD

1,25D

1818


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HOW A CELL RESPONDSHOW A CELL RESPONDS25(OH)

D

newly synthesizedcellular equipmentResponse

Signal/

Demand

1,25(OH)2D is the key

that unlocks the DNA library

1919


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VIT DVIT D CANONICALCANONICAL

SCHEMESCHEME

skin liver kidney gutCaBP1,25(OH)2D325(OH)D3D3

2020


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VIT DVIT D EXPANDED SCHEMEEXPANDED SCHEME

endocrine gutidney CaBP1,25(OH)2D3

2121

25(OH)D3

~5%

peripheryskin liver

varioustissuesD31,25(OH)2D3

85+%

autocrine cellsignals


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How much Vitamin D is enoughand how can this be achieved?


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VITAMIN DVITAMIN D SourcesSources

150

200

2000

Body D3stores 25(OH)D

typical input,all sources:~2350 iu


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Vitamin D normal levelVitamin D normal level

and supplementationand supplementation

Serum 25(OH)D from 50 to ~80 nmol/L ( 30 ng/ml) isneeded to improves Ca absorption, raises BMD, andreduces falls and osteoporotic fracture risk. Aconcentration of 75-125 nmol/l has been recommended.

Heaney the American journal of clinical nutrition 2004

Serum 25(OH)D rises by ~ 1 ng/mL (2.5 nmol/L) forSerum 25(OH)D rises by ~ 1 ng/mL (2.5 nmol/L) for

every 100 additional IU/d of vitamin Devery 100 additional IU/d of vitamin D33

To raise a patient level from 15 to 30 ng/mL willTo raise a patient level from 15 to 30 ng/mL will

typically require an additional input of 1500 IU/d,typically require an additional input of 1500 IU/d,

however there is huge variability around this averagehowever there is huge variability around this average

2424


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VITAMIN DVITAMIN D SourcesSources

150

200

2000

Body D3stores 25(OH)D

needed input,all sources:~4000 iu


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A VITAMIN D THRESHOLDA VITAMIN D THRESHOLD

SERUM 25(OH)D (nmol/L)

0 20 40 60 80 100 120 140 160

ABSORPTION

FRACTION

0.0

0.1

0.2

0.3

0.4

0.5

physiologicalregulation no longerlimited by vit Davailability

2626


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VIT DVIT D EXPANDED SCHEMEEXPANDED SCHEME

25(OH)D3D3

1,25(OH)2D3skin liverperiphery

gutidney CaBP

1,25(OH)2D3

varioustissues

endocrine

autocrine cellsignals

Is replacing vitamin D 1, 25 OH is enough ?


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Safety


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VITAMIN D INTAKE & TOXICITYVITAMIN D INTAKE & TOXICITY**

0

200

400

600

800

1,000

1,200

1,400

1,600

1,800

1,000 10,000 100,000 1,000,000 10,000,000

Vitamin D Intake (IU/day)

Serum2

5(OH

)D

(nmol/

L)

15 studies of adultsreceiving vitamin Dsupplementation(means)

8 studies reportingtoxicity (individualvalues)

no toxicity below 500nmol/L (200 ng/mL)

no toxicity below30,000 IU/d

* Hathcock J N et al.Am J Clin Nutr. 2007;85:618.


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Maximum safe Total

daily intake: 10,000IU/d*

*Hathcock et al.,(2007) AJCN 85:618


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D2 Vs D3


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DD22 vs. Dvs. D33**AUCAUC

TIME (days)

0 5 10 15 20 25 30

25(OH)D

(nmol/L)

-10

-5

0

5

10

15

20

25

D3

D2

AUC

28

0

100

200

300

400

500

600

D2

D3

*Armas et al., 20043232


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Beyond Osteoporosis

I d l t


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Immunomodulatory

Effects of Vitamin D A major noncalciotropic function of 1,25-(OH)2-D is in the regulation

of the immune system.

Vitamin D play an important role in both innate and Adaptiveimmunity.

Recent studies showed a potential therapeutic role of vitamin D, itsmetabolites and its analogues for infectious and auto-immunedisorders in humans

Patients with rickets have impaired macrophage phagocytic function ,

which could be reversed by 1,25- (OH)2-D repletion.

Recent studies have also shed new light on the mechanism of theantimicrobial action of 1,25-(OH)2-D.


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Vitamin D and Innateimmunity

&


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VITAMIN D & INNATEVITAMIN D & INNATE

IMMUNITY*IMMUNITY*

activatedToll-likereceptor

*Liu et al., Science 2006

&VITAMIN D & INNATE


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IMMUNITY*IMMUNITY*

Cathelicidinactericidalpeptide




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IMMUNITY*IMMUNITY*

HumanHumanMacrophagMacrophag

es in fetales in fetal

calf serumcalf serum

Cyp27B1VDRthe Vit D1- hydroxylasethe Vit Dreceptor




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IMMUNITYIMMUNITY** HumanHuman

macrophagmacrophag



Cyp27B1VDR

fetal calf

serum is lowin both25(OH)D &1,25(OH)2D




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IMMUNITYIMMUNITY**

HumanHumanmacrophagmacrophag



addadd1,25(OH)1,25(OH)22DD

to theto the

system

Cyp27B1VDR1,25DCathelicidinCyp24

system




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IMMUNITY*IMMUNITY*

HumanHumanmacrophagmacrophag



addadd25(OH)25(OH) DD

to theto the

systemsystem

Cyp27B1VDR1,25DCathelicidinCyp24

25OHD


VITAMIN D &VITAMIN D &


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VITAMIN D &VITAMIN D &

TUBERCULOSISTUBERCULOSIS Human macrophagesHuman macrophages

activated withactivated with M.M.

TuberculosisTuberculosisandand

incubated in humanincubated in human

serumserum

AfricanAfrican--AmericanAmerican WhiteWhite

AfricanAfrican--AmericanAmerican

with addedwith added

25(OH)D25(OH)D0

1

2

3

4

A-A W A-A+25D

Cathelicidin mRNA


serum 25(OH)D:22 nmol/L

serum 25(OH)D:78 nmol/L


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VITAMIN D & TUBERCULOSISD & TUBERCULOSIS

Vitamin D is an essential mediator in the innate immuneVitamin D is an essential mediator in the innate immune

responseresponse

Serum 25(OH)D is the critical variableSerum 25(OH)D is the critical variable

25(OH)D is the rate25(OH)D is the rate--limitinglimiting

4343


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VITAMIN D & TUBERCULOSIS*VITAMIN D & TUBERCULOSIS*

67 pts with pulmonary67 pts with pulmonaryTBTB

standard treatment forstandard treatment forallall

in addition, randomizedin addition, randomizedto either vit D 10,000to either vit D 10,000IU/d or placeboIU/d or placebo

50

60

70

80

90

100

Placebo Vit D

Sputum Conversion (%)

P = 0.002

*Nursyam et al., Acta Med Indones 20064444


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Most recent articles A single oral dose of 2.5 mg vitamin D2 improve week one

level but not week 8. (int J Tuberc lung dis Jan 2009) Wagner et al Dec 2008. Dose Vitamin D makes the World go

round?

Cochrane Database syst rev. Oct 2008. There were not

enough evidence to assess the effect of vitamin D on TB.Trials in progress

Enhancing the innent immunity in TB for example is clearly

beneficial but potentiating of the pro inflammatory processescan increase tissue destruction.

Vitamin D and the immune


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response to Mycobacteriumtuberculosis


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VITAMIN D & INFLUENZA*VITAMIN D & INFLUENZA*

208 African208 African--American,American,postmenopausal womenpostmenopausal women

3 yr DB3 yr DB--RCTRCT

placebo or vit Dplacebo or vit D33

800 IU/d800 IU/d 2 yrs2 yrs 2000 IU/d2000 IU/d 33rdrd yryr

basal 25(OH)D: 18.8basal 25(OH)D: 18.8 7.57.5

0

5

10

15

20

25

30

35

Placebo Vitamin D

P < 0.002

*Aloia & U-Ng (2007) Epidemiol & Infect4747

Vitamin D and auto-


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Vitamin D and auto

immune disorders Major effect of 1,25-(OH)2-D on the immune system is the

suppression of the adaptive immune

This seems to be beneficial in Autoimmunity.

Epidemiologic reports have correlated limited sunlightexposure, reduced dietary vitamin D intake or 25-OH-D levelswith a number of auto-immune diseases

Studies have shown effectiveness of 1,25-(OH)2-D and its

analogs in a variety of animal models of these autoimmunedisorders


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Multiple sclerosis

The prevalence of multiple sclerosis (MS) is well known to

increase with latitude both north and south of the equator

the role of sunshine was proposed several decades ago, andrecent studies have provided evidence that high levels of

vitamin D may decrease the risk of MS.

Intake of vitamin D from diet and from supplements wasinversely associated with risk of MS in the Nurses Health

Study and Nurses Health Study II


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Systemic lupus Erythematosus

The greater incidence of (SLE) in African-Americans and increasedmorbidity and mortality compared to Caucasians has been attributed

to lower serum 25-OH-D concentrations

In a group of lupus patients, severe D deficiency was associated withhigher disease activity measures but lower levels of antibodies todouble-stranded DNA than in patients with normal serum D

On the other hand, vitamin D intake from food and supplements wasnot associated with risk of SLE in the Nurses Health Study andNurses Health Study II

The role of vitamin D deficiency in the pathogenesis of SLE andwhether vitamin D supplementation can improve the course of thedisease is still not entirely proven.

M l i l l i


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Multiple sclerosis

The risk of MS significantly decreased with increasing levels of25-OH-D .This was found in a study done on stored serumsamples for more than 7 000 000 US military personnel in

D.O.D.

Studies in experimental animal model for human MSdisease, also suggest a protective role of active D in MS,through inhibition of monocyte trafficking to the centralnervous system, and suppression of chemokine synthesis

In a recently published small, uncontrolled pilot study,administration of high doses of vitaminD(up to 280 000

IU per week) to MS patients was a associated with atendency toward a decrease in the number ofgadolinium-enhancing lesions per patient

Jan 2009 in Mult Scler: a study concluded that higherlevels of vitamin D OH are associated with lower incidentof Ms in women only


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Antiproliferative propertiesof vitamin D

Antiproliferative properties of


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p p p

vitamin D A major noncalciotropic action of 1,25-(OH)2-D is its modulation

of benign and malignant hyper proliferative conditions.

The antineoplastic properties of 1,25-(OH)2-D includeregulating apoptosis and angiogenesis, and promoting cellularproliferation of normal and cancerous cells while inducing theirterminal differentiation

Calcipotriol (calcipotriene),a synthetic 1,25-(OH)2-D analog, hasbecome first-line therapy for plaque psoriasis, either asmonotherapy or in combination

Antiproliferative properties


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Antiproliferative properties

of vitamin D In a 4-year study of 1179 community-dwelling postmenopausal

women randomly assigned to calcium supplementation alone,

calcium and vitamin D supplementation ,or placebo, cancer incidencewas significantly lower in the calcium and vitamin D supplementedwomen than in the placebo control subjects (P


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VITAMIN D & CANCERVITAMIN D & CANCER

**

1179 healthy women1179 healthy women

aged 66.7aged 66.7 7.37.3 four year trialfour year trial

1032 finished (87.5%)1032 finished (87.5%)

baseline 25(OH)D: 71.8 nmol/Lbaseline 25(OH)D: 71.8 nmol/L 20.320.3 three treatment groups:three treatment groups:

controlcontrol

Ca (1400Ca (14001500 mg/d)1500 mg/d) Ca plus DCa plus D33 (1100 IU/d)(1100 IU/d)

achieved 25(OH)D: 96 nmol/Lachieved 25(OH)D: 96 nmol/L 21.421.4

*Lappe et al. AJCN 20075555

VITAMIN D & CANCER*


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VITAMIN D & CANCERVITAMIN D & CANCER

**

Time (yrs)0 1 2 3 4

FaoCne-e

0.90

0.92

0.94

0.96

0.98

1.00

Ca+D

Placebo

Ca-only P < 0.01RR = 0.402


VITAMIN D & CANCER*VITAMIN D & CANCER*


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Time (yrs)0 1 2 3 4 5

FaoCne-e

0.90

0.92

0.94

0.96

0.98

1.00

Ca+D

Placebo

Ca-only


96 nmol/L

71.8 nmol/L



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Time (yrs)0 1 2 3 4 5

FaoCne-e

0.90

0.92

0.94

0.96

0.98

1.00

Ca+D

Placebo

Ca-only RR = 0.232


Vitamin D and Colon Cancer


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Vitamin D and Colon Cancer

Epidemiologic studies have described inverse associationsbetween biomarkers of sunlight exposure , dairy products ordietary vitamin D and the risk of various malignanciesincluding colon cancer ,prostate cancer, breast cancer , andpancreatic cancer

The largest randomized placebo-controlled study of vitamin Dand the risk of colon cancer is the Womens Health Initiative.The incidence of invasive colorectal cancer after 7 years didnot differ significantly. N Engl J med feb 2006

In the (NHANES) III, serum 25-OHD levels was notassociated with total cancer mortality, although in the samestudy, individuals with higher 25- OH-D levels had significantly

lower risk of colon cancer mortality


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COLORECTAL CANCERCOLORECTAL CANCER NursesNursesHealth StudyHealth Study

ages 46ages 467878

nested casenested case--controlcontrol

studystudy

193 incident cases193 incident cases 25(OH)D measured25(OH)D measured

twice, prior to diagnosistwice, prior to diagnosis

Feskanich et al., CancerFeskanich et al., Cancer

Epidemiol Biomarkers PrevEpidemiol Biomarkers Prev2004 13:15022004 13:15020808

0.0

0.2

0.4

0.6

0.8

1.0

Odd

sRatio

1st16

2nd22

3rd27

4th31

5th

40

25(OH)D Quintiles (with medians*)

P=0.02

*ng/mL


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COLORECTAL CANCERCOLORECTAL CANCER

5 prospective5 prospective

studiesstudies

> 200,000> 200,000

individualsindividuals

430 cases430 cases

ORs computed forORs computed for

25(OH)D quintiles25(OH)D quintiles

Garland et al,Garland et al,20052005

Serum 25(OH)D (nmol/L)

0 20 40 60 80 100 120

Odd

sRa

tio

0.0

0.2

0.4

0.6

0.8

1.0

P < 0.001

6161

Vitamin D and Prostate


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Cancer Epidemiological studies have yielded inconsistent associations

between vitamin D status and prostate cancer risk.

A nested case control study as part of the Prostate, lung,colorectal and ovarian cancer screening trail projectconcluded that Vitamin D is not associated with decrease

prostate ca risk, higher circulating vitamin D was a associatedwith increased risk of aggressive disease. J Natl cancer Inst.June 2008

In men with advanced, androgen-insensitive prostate cancertreatment the use of a Vitamin D analog, was associated withimproved survival, although it did not produce a statisticallysignificant improvement in the PSA response rate

VITAMIN D & PROSTATE CA*VITAMIN D & PROSTATE CA*


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VITAMIN D & PROSTATE CAVITAMIN D & PROSTATE CA

Nested CaseNested Case

control study incontrol study inthe Helsinki heartthe Helsinki heart

StudyStudy

19,000 men19,000 men

F Up for 13 yearsF Up for 13 years

149 cases prostate149 cases prostate

CACA

*Ahonen et al., CancerCauses&Control 11:847-852 (2000) 25(OH)D QUARTILES1 2 3 4

RAVRSK

0.0

0.5

1.0

1.5

2.0

2.5

Pfortrend=0.01

VITAMIN D & PROSTATE CAVITAMIN D & PROSTATE CA**


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VITAMIN D & PROSTATE CAVITAMIN D & PROSTATE CA

Those belowThose below

the medianthe median

25(OH)D level25(OH)D level

were 70%were 70%

more likely tomore likely todevelopdevelop

prostate CAprostate CA

than thosethan thoseaboveabove

*Ahonen et al., CancerCauses&Control 11:847-852 (2000) 25(OH)D QUARTILES1 2 3 4

RAVRSK

0.0

0.5

1.0

1.5

2.0

2.5

Pfortrend=0.01

Vitamin D and BreastVitamin D and Breast


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Cancer RiskCancer Risk WHI again reported that ca and vitamin D supplement did

not decrease the risk of Breast ca.

Epidemiological studies from premenopausal women suggestthat vitamin D supplementation may prevent breast ca in

these women. Lin et al Arch Intern Med 2007

Further studies to address the issues of higher dose of vitamin

D and the risk of breast cancer are needed.

BREAST CANCER RISKBREAST CANCER RISK


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BREAST CANCER RISKBREAST CANCER RISK

CaseCase--control studycontrol study

1394 cases1394 cases 1365 controls1365 controls

Pre menopausalPre menopausal

Odds ratio for CAOdds ratio for CA

inversely associatedinversely associatedwith vit D statuswith vit D status

[25(OH)D][25(OH)D]

Abbas et al., CarcinogenesisAbbas et al., Carcinogenesis

(2008) 29:93(2008) 29:93990.0

0.2

0.4

0.6

0.8

1.0

1.2

Hazard

Ratio

75

69 %decrease in

risk

99

Serum 25(OH)D (nmol/L)


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MAMMOGRAPHIC DENSITIESMAMMOGRAPHIC DENSITIES

543 women aged 40543 women aged 406060 198919899090

dietary intakes assesseddietary intakes assessed

with FFQwith FFQ

odds ratios developed forodds ratios developed for

70% of film70% of film

with densitieswith densities

[Berube et al., 2004; Cancer[Berube et al., 2004; Cancer

Epidemiol Biomarkers PrevEpidemiol Biomarkers Prev

13:146613:146672]72]0.0

0.2

0.4

0.6

0.8

1.0

Odds

Ratio

1st 2nd 3rd 4th

Quartiles

Vit D

CaP


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disease/risk

factors In the Framingham Offspring Study, 25-OH-D deficiency was

associated with incident cardiovascular disease, particularly in

hypertensive individuals

This may be due to the association of lower 25-OH-D levels with anumber of traditional cardiovascular risk factors.

The association between obesity and hypovitaminosis D may be inpart due to reduced vitamin D bioavailability from sequestration inadipose tissue

From a cross-sectional analysis of data from the third national healthand nutrition examination indicated a strong and independentrelationship between vitamin d deficiency and the prevalence of

CVD. Atherosclerosis Nov 2008


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VIT D & CARDIOVASCULAR DISEASEVIT D & CARDIOVASCULAR DISEASE

1739 Framingham Offspring1739 Framingham Offspringmembersmembers

age: 59 yrsage: 59 yrs

followfollow--up: 5.4 yrsup: 5.4 yrs

120 individuals developed a120 individuals developed aCV eventCV event

HR calculated againstHR calculated against

25(OH)D values > 15 ng/mL25(OH)D values > 15 ng/mL

Wang et al. Circulation 2008Wang et al. Circulation 2008 0.0

0.5

1.0

1.5

2.0

2.5

3.0

3.5

Hazar

d

Ratio

< 10

ng/mL

< 15

ng/mL

> 15

ng/mL

80 % increasein risk

53 % increasein risk

6969

Hypertension riskHypertension risk


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Hypertension riskHypertension risk

Recent reports on the relationship between vitamin D and the

risk of hypertension from three large independent prospectivecohorts, the Nurses Health Study I and II, and the HealthProfessionals Follow-up Study have yielded conflicting results

While intake of vitamin D was not associated with the risk ofdeveloping hypertension, lower serum 25-OH-D levelsconferred a greater risk for the incident hypertension

Forman et al Nov. 2008 in Hypertension found that in youngwomen vitamin D level was inversely and independentlyassociated with the risk of developing hypertension

VIT D & BLOOD PRESSURE*VIT D & BLOOD PRESSURE*


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VIT D & BLOOD PRESSUREVIT D & BLOOD PRESSURE

148 women, aged 74148 women, aged 74

11

DBDBRCTRCT

baseline 25(OH)D


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VIT D & BLOOD PRESSURE& OO SSU

1811 men & women1811 men & women

with measuredwith measured25(OH)D levels**25(OH)D levels**

4 yrs4 yrsobservationobservation

97 cases of incident97 cases of incidenthypertensionhypertension

RR computed forRR computed for

25(OH)D 30 ng/mL

*Forman at al., 2007;Hypertension 49:1063

** Health Profs Follow-up Study & Nurses Health Study

>30


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DIABETES & 25(OH)DDIABETES & 25(OH)D

Scragg et al., 2004Scragg et al., 2004Diabetes CareDiabetes Care27:281327:28131818

NHANESNHANES--IIIIII

6,228 adults6,228 adults plasma glucoseplasma glucose

independentlyindependentlypredicted by BMI &predicted by BMI &

serum 25OHDserum 25OHD(fasting and 2 hr(fasting and 2 hrpost load)post load)

0.0

0.1

0.2

0.3

0.4

0.5

0.6

0.70.8

0.9

1.0

Relat

iveRisk

1st 2nd 3rd 4th

25(OH)D Quartiles

White

Hispanic

7373

NEONATAL VIT D & DIABETESNEONATAL VIT D & DIABETES**


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10,366 northern10,366 northern

Finnish childrenFinnish children

2000 IU Vit D/d 12000 IU Vit D/d 1stst

year of lifeyear of life

prevalence ofprevalence oftype I diabetestype I diabetes

assessed at age 21assessed at age 21

RR calculated vs. noRR calculated vs. nosupplementationsupplementation

Vi tam in D Ad m in is t ra t ionR e g u

la rIr re g

u la r? r ic

k e ts

RelatvRisk

0.01

0 .1

1

10

*Hypponen et al., Lancet 2001;358:150003

7474

OTHER CHRONIC


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DISEASES?Disease Status of Evidence

++++++++++++++++++++++++

++++++++++++

osteoporosis osteoarthritis falls/neuromusc. fcn multiple sclerosis fibromyalgia-like syndrome type I diabetes insulin sensitivity cardiovascular disease periodontal disease

various cancers tuberculosis hypertension

7575


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Bone health and Skeletal

health

Serum 25(OH)D and Hip BMDSerum 25(OH)D and Hip BMD


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( ) p

NHANESNHANES--IIIIII Adults AgeAdults Age

2020 49 yrs49 yrs

Lowest plot ofLowest plot of

differencedifferencefrom lowestfrom lowestquintile

Non-Hispanic whites

African-Americans

Hispanics

quintile

Bischoff-Ferrari HA. Am J Med 2004; 116: 634-9.

VITAMIN D & FRACTURE RISKVITAMIN D & FRACTURE RISK


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0 25 50 75 100 125 150

FRACTURERELATIV

ERISK

(hip,forearm,spin

e)

0.0

0.2

0.4

0.6

0.8

1.0 N = 2,686

ages 6585

5 yr RCT

Vit D 800IU/d

Trivedi et al.BMJ 2003;326:469

33%

(nmol/L)

7878

VIT D & NEUROMUSCULAR FUNCTION*VIT D & NEUROMUSCULAR FUNCTION*


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VIT D & NEUROMUSCULAR FUNCTION

1359 men & women;1359 men & women;

mean age 75.5mean age 75.5 Amsterdam longitud.Amsterdam longitud.

aging studyaging study

neuromuscularneuromuscular

performanceperformancemeasured on a scalemeasured on a scaleof 0 to 12 (higher isof 0 to 12 (higher isbetter)better)

0

1

2

3

4

5

6

78

9

75

SERUM 25(OH)D

Performance Score

each step statisticallysignificant

*Wicherts et al. JBMR. 2005.

VITAMIN D & RISK OF FALLING*VITAMIN D & RISK OF FALLING*


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122 women122 women

Age: 63Age: 639999

DBDB--RCTRCT

Ca 1,200 mg/dCa 1,200 mg/d

Ca + 800 IU Vit DCa + 800 IU Vit D

12 week duration12 week duration

25(OH)D 12 ng/mL at25(OH)D 12 ng/mL atbaselinebaseline 0.0

0.2

0.4

0.6

0.8

1.0

FallRisk

Ca only Ca + D

49%

*Bischoff et al. JBMR. 2003;18:343351. 8080


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Thank you

Special thanks to Dr. RobertHeaney for allowing me to use

some of his slides

Osteoporosis Vitamin d Deficiency Nahrain Al Zubaidi Md

Documents

Transcript of Osteoporosis Vitamin d Deficiency Nahrain Al Zubaidi Md