Dr.Seeva SivakumaranSenior Staff SpecialistThe Canberra Hospital22-08-2007

Calcium and vitamin D:who, when, why and how much?

Seeva Sivakumaran Senior Staff Specialist

Aged Care & Rehabilitation ServiceThe Canberra Hospital

Agenda

Osteoporosis size of the problem Calcium and vitamin D in bone metabolismOsteoporosis prevention and management:

the roles of calcium and vitamin D Recommended daily intakes Sources of calcium and vitamin D Targeting patients with inadequate intake

Conclusions

The ageing population

In developing countries

0 - 15 years 30 %

Over 65 years 5.5 %

But changes are expected…

“…a systemic skeletal disease characterized by low bone mass and micro-architectural deterioration of bone tissue, leading to enhanced bone fragility and a consequent increase in fracture risk.”

Definition of osteoporosis

World Health Organization (WHO), 1994

Cooper et al. Trends Endocrinol Metab 1992; 3:224

755535

Men

Forearm

Vertebrae

Hip

Age (years)

4,000

3,000

2,000

1,000

Inci

den

ce p

er 1

00,0

00 p

ers

on-y

ear

s

Women

Forearm

Vertebrae

Hip

55 7535

Osteoporotic fracture incidence

normal osteoporotic

Trabecular bone

Bone quality is not the only factor …Bone quality is not the only factor …

STATISTICS OF THE SILENT EPIDEMIC SOURCE (AIHW) AUSTRALIAN INSTITUDE OF HEALTH AND WELFARE

1,014 over 65 died due to accidental falls in 19981998 45,000 hospitalised due to falls 25 % Australian females & 17% men will develop

osteoporosis. 1 in 2 women and 1 in 3 men over 60 will sustain an

osteoporotic fracture. Of all # 46% vertebral,16% hip, 16% wrist 50% spinal # do not come to attention!80% patients with osteoporotic # do not receive

preventative RX

OSTEOPOROSIS PREVALENCE

2002, 1.9 million Australians had osteoporosis.65,514 Australians hospitalised with osteoporotic # 2002 = 177 hospitalisations per dayCurrently a # every 8.1 minutes2021 one # every 3.7minutes Osteoporosis:

as common as hypertension.more common than hyperlidaemia allergies & the

common cold.

MORBIDITY & MORTALITY

20% with hip # will die wihin 6 months.

Death rate due to hip # is > all female cancers

combined

50% patients with hip fracture require long-term nursing

care.

By 2020 1 in 3 hospital beds will be occupied by women

with fractures.

Bone massBone structureBone quality

Fall RiskImpact of

fallSkeletalstrength

Fracture risk

Type of fallEnergy reductionExternal protection

Neuromuscular functionEnvironmental risksAge

Pathogenesis of fragility fractures

Calcium and vitamin D in bone metabolism

Skeletal roles of calcium & vitamin D

CalciumProvides structural

integrity of skeletonEverybody needs adequate

calcium intake, but especially those at risk for osteoporotic fractures

Vitamin DBone mineralisation Calcium absorption from

small intestineExtracellular calcium

homeostasisDeficiency predicts falls in

elderly women in nursing homes

ANZBMS Med J Aust 2005; 182: 281-285; OA & ANZBMS Medicine Today 2005; 6: 43-50.

Calcium and osteoporosis

The role of calcium

Calcium is required on a daily basis

• Calcium provides strength to the skeleton 1

Calcium is the substrate for bone mineralisation Skeletal mass cannot be built or maintained if

calcium intake is insufficient or calcium losses are excessive

• 99% of calcium is located in the skeleton 2

• Bone is the reservoir for calcium and replenishes extracellular fluid (ECF) losses 2

• Calcium plays a role in muscular, neural and most metabolic processes 2

1. Heaney RP. Calcif Tissue Int 2002; 70: 70-73. 2. FAO/WHO expert consultation on human vitamin and mineral requirements, Update March 2002

FAO/WHO expert consultation on human vitamin and mineral

requirements, Update March 2002; HP Kruse, Grundzüge der

Osteologie, Springer Verlag 1984

Calcium balance (equilibrium) for post-menopausal women reached at intake of ~1000 mg/ day

Calcium dietary intake 700 – 1000 mg/d

20-35%

100 – 300 mg/d

50-250 mg/d500 mg/d

500 mg/d

450 – 900 mg/d

Calcium homeostasis Relationship between calcium intake and calcium absorption /excretion

Plasma & ECFCalcium

9.0 – 10.5 mg/100ml

PTH, 1,25(0H)2D

PTH -

PTH

PTH, 1,25(0H)2D

GH, PO4, Sex hormones, Calcitonin

Calcium in osteoporosis treatment

Adequate calcium intake is vital1

Most osteoporosis treatments tested with calcium supplementation (500–1000 mg/day)

Moderately effective as monotherapy1,2 BMD (approximately 1-2% over 2-3 years)

Use calcium/vitamin D in institutionalised elderly to prevent non-vertebral fractures3

1. OA & ANZBMS Medicine Today 2005;6:43-50; 2. Sambrook PN et al, Med J Aust 2002;176:S1-S15; 3. Chapuy MC et al, N Engl J Med 1992;327:1637-42.

Sub-optimal calcium intake in Australia

87% of women 55 years and older have calcium intakes below the recommended dietary intake (Geelong Osteoporosis Study )1

1. Pasco J et al. Aust NZ J Med 2000; 30: 21-27.

Sub-optimal calcium intake in Australia

Mean daily calcium intake Geelong Osteoporosis Study 1

646mg/day among women aged 55-92

National Nutrition Survey 2 685.6mg/day for females aged 65 and over 795.6mg/day for males aged 65 and over

Recommendations: NHMRC 1999 3:

1000mg/day for women aged 54 or over 800mg/day for males aged 64 or more

ANZBMS – OA - Ca & Vit D Forum 2005 4: 1000mg/day for adults 1300mg/day for people over 70 years

1. Pasco J et al. Aust NZ J Med 2000; 30: 21-27. 2. National Nutrition Survey – ABS 1995. 3. National Health and Medical Research Council. Australian Government Publishing Service, 1999. 4 Calcium, Vitamin D and Osteoporosis – A guide for GPs – Osteoporosis Australia – In press - 2006

► Gap of 400 – 600 mg Calcium/day

Calcium supplementation in Osteoporosis

Chapuy et al. BMJ 1994; 308:1081-1082

0

5

10

15

20

25

30

NonvertFractures

Hip Fractures

Placebo

Calcium + Vit D3

% P

ati e

nts

wi t

h f

ract

ure

s

17%* Relative Risk Reduction

23%* Relative Risk Reduction

ITT Analysis

* p<0.02

Effect of calcium and vitamin D treatment for 3 years on hip fractures in elderly women 3270 mobile elderly women (mean age 84) living in nursing homes Calcium 1.2g/day (in the form of tricalcium phosphate) + Vit D3 800IU/day vs placebo

Calcium supplementation in Osteoporosis

Evidence to demonstrate a reduction in fracture risk with increased calcium intake alone

Reid I et al. 1995 American Medical Journal 98: 331-335

Calcium n=38Mean age : 58+4 yrs

9+4 yrs since m’pause

Placebo n=40Mean age : 59+6 yrs

10+5 yrs since m’pause

78 postmenopausal women completed 4 years of the study

Adult men and women 1000 mgWomen over 50 yrs 1300 mg*Men over 70 yrs 1300 mg*Pregnant women 1100 mg Lactating women 1200 mg

*Generally not feasible from diet alone

Recommended calcium intake

Osteoporosis Australia. Calcium, Vitamin D and Osteoporosis – A Guide for GPs 2nd edn

Calcium content of common foods

Osteoporosis Australia. Calcium, Vitamin D and Osteoporosis – A Guide for GPs 2nd edn

Who needs more calcium?

Risk factors for inadequate dietary calcium intake include:1

old agesocial disadvantagemalabsorption due to gastrointestinal diseasecorticosteroid usesex hormone deficiency.

Intake < RDI for 75%-87% Australian women2,3

Average 646 mg/day for women >55 years in Geelong Osteoporosis Study (1300 mg/day recommended)

Low intakes of cereal, milk, cheese, yoghurt41. OA & ANZBMS Medicine Today 2005;6:43-50; 2. Sambrook PN et al, Med J Aust 2002;176:S1-S15; 3. NHMRC 2003; 4. Jean Hailes Foundn. Med J Aust 2000; 173 Suppl 6 November: S95-S96.

Dietary sources of calcium

Dairy foodsMost readily absorbed form of

calciumMain source of calcium in

Australian dietsRDI = 3 serves per day

Calcium-enriched soy drinksFish with bones

(e.g. tinned salmon)

Australian Food and Nutrition Monitoring Unit 2001; OA & ANZBMS Medicine Today 2005;6:43-50; Sambrook PN et al, Med J Aust 2002;176:S1-S15; Osteoporosis Australia. Calcium, Vitamin D and Osteoporosis – A Guide for GPs 2nd edn

RDI for older people = 1300 mg

= 4.5 glasses of milk

Vitamin D and osteoporosis

Vitamin D deficiency is commonVitamin D deficiency: an emerging public health

problem in Australia1 (all over the world)

Deficiency bone pain, muscle weakness, osteoporosis, falls, fractures1

60% of postmenopausal Australian women with osteoporosis had low serum vitamin D (<30 ng/mL)2*

* International study of 2606 postmenopausal women with osteoporosis, including 204 women from Australia

1. Osteoporosis Australia. Calcium, Vitamin D and Osteoporosis – A Guide for GPs 2nd edn2. Lips P et al. J Int Med 2006; 260:245-254.

Vitamin D is a Hormone or a Vitamin ?

Vitamin D fits the definition of a

Vitamin and that of a Hormone

HORMONEA messenger produced and secreted by specific glands or

cells within the body of animals. Transported through the blood stream to designated target

organs. Binds to its specific receptor delivering its message to a

specific set of cells.

VITAMINA substance regularly required by the body in small

amounts.The body cannot make vitamins.Must be supplied in diet.

Vitamin D : A Hormone & A Vitamin

Regulation of calcium homeostasis and bone mineralizationPromotes intestinal absorption of calciumPromotes resorption of ca++ in kidneysMobilizes Ca from bones thereby initiating bone remodeling

process at the same time promotes Ca Po4 into rachitic and osteoporotic bones

Supplementary functions:Helps to regulate immune system Regulates cell differentiation and cell proliferationWorks synergistically with vitamin A to induce certain cancer

cells to differentiate in to normal cells and to inhibit cancer cell proliferation

Classical functions of vitamin D:

Reduction to risk of: Osteoporosis (+ calcium supplement). Senile cataract, glucose intolerance Polycystic ovarian syndrome (+ calcium supplement). Reduced lipid peroxidation and increased enzymes protecting

oxidation SAD - Seasonal affective disorderRole and association with: Infection control and inflammatory immune function Infertility Multiple sclerosis, sjogrens, rheumatoid arthritis, thyroiditis,

crohns, and some cancers eg bowel, prostate, breast Activated vit D in adrenals regulate tyrosine hydroxylase the rate

limiting enzyme necessary for dopamine, epinephrine and nor epinephrine production (?Schizophrenia)

Misdiagnoses: Fibromyalgia (Vitamin D deficiency)

Early symptoms of vitamin D deficiency (Osteomalacia)

Muscle pain mainly shoulder /hip girdle Recurrent falls and difficulty transferring in elderlyRecurrent fracturesPoor fracture healingBone pain particularly with bisphosphonates

Premature OAMayo clinic proceedings Dec 2003 Plotnikoff GA QuicgleyJM Prabhala A Arch Intern Med 2000Al Faraj et al Spine 2003PfeiferM et al J Bone Miner 2000M.Hollick Vit D Millinium Perspective J Cell Biochem 2003

Latitude > 45 or higher even summer sun is too weak to produce enough vitamin D

CANBERRA -35.27 southBRISBANE 27 south

Latitude and Vitamin D

Factors affecting Vitamin D production on skin

Season Geographic latitudeTime of dayCloud /fogSun screenAgeing skin Excess skin coverWindow glassIndoor life style

Latitude /Vit D related diseases

Multiple sclerosisBreast cancerProstate cancer Insulin dependent diabetes Colorectal cancerSchizophreniaHeart disease

Vitamin D may be more important to colon cancerprevention than previously believed

Journal of the American Medical Assocition Vol 290 No 22

Recommended sun exposure (minutes) for moderately fair skin

Time (adjust for daylight saving or pigmented skin)

Dec-Jan 10:00 or 14:00

July-Aug10:00 or 14:00

July-Aug12:00

Cairns 6-7 9-12 7Brisbane 6-7 15-19 11

Perth 5-6 20-28 15

Sydney 6-8 26-28 16

Adelaide 5-7 25-38 19

Melbourne 6-8 32-52 25

Hobart 7-9 40-47 29

ANZBMS Med J Aust 2005; 182: 281-285.

Point of regulation of conversion of Vit D to active form is by I hydroxylase in kidney

Production of Vit D in the skin is determined by latitude

Latitude higher than 30 south and north have insufficient UVB 2-6 months of the year at mid day

Latitude higher than 40 has 6-8 months devoid of adequate UVB

Control of production of active Vitamin D (calcitriol)

ENTIRE NEED FOR VITAMIN D CAN BE MET BY THE BODY BY ADEQUATE EXPOSURE TO SUN LIGHT.

THE BODY DOES NOT OVERPRODUCE VIT D AS PROLONGED EXPOSURE PRODUCES INACTIVE METABOLITES

IN THE ABSENCE OF ADEQUATE TO SUN EXPOSURE THE BODY DEPENDS ON DIETARY SUPPLY FOR VITAMIN D

Daily need of Vitamin D

Who may need extra Vitamin D

Infants who are exclusively Breast FedOlder adultsPersons with limited sun exposurePeople with pigmented skinPatients with malabsorptionPatients on prednisolone & thyroid

supplements and those on antiepileptic

Dietary supplements Fact Sheet Vit D National Inst. Of Health

Current Problems with Vitamin D administration

Recommended Daily Allowance (RDA) is probably set too lowLab normal range is set too lowPoor dietary intake -- Diet poor substitute for sun Lack of food fortificationHigh Dose Vit D3 Not available in AustraliaCalcitriol available on PBS but not appropriateMany patients on bisphosphonates with no Vit D or CaCaution – for those with sarcoidosis lymphoma renal failure but

restoring physiological Vit D levels will help many more pts than it will hurt !

Vitamin D Council

Vitamin D supplementationUse formulations with sufficient dose:

Ostelin (ergocalciferol 25 µg = D2 1000 IU)Ostevit D, Blackmores Vitamin D (cholecalciferol =D3 1000 IU)Ostelin Vitamin D & Calcium (cholecalciferol = D3 500 IU) Doses in calcium and multivitamin preparations too low for

treatment of deficiency Cod liver oil contains vitamin A, which may increase

fracture riskDosing

Supplementation: 1000 IU per day Moderate-severe deficiency: 3000–5000 IU per day for

6–12 weeks then maintenance. Check blood level at 3 monthsCosts approximately 24 cents/day for supplementation

ANZBMS Med J Aust 2005; 182: 281-285.

Pivotal trials – Calcium and Vit D supplementation

Trial Calcium Vit D

Alendronate 1-3 FIT 1 If daily intake <1000 mg/day – 500 mg/day – 82% of patients

If daily Ca intake <1000 mg/day – 250 IU/day – 82% of patients

FIT 2 If daily intake <1000 mg/day – 500 mg/day – 82% of patients

If daily Ca intake <1000mg/day – 250 IU/day – 82% of patients

FOSIT 500 mg/day - 100% of patients

Risedronate 4-8 VERT-MN 1000 mg/day – 100% of patients If <40 nmol/l up to 500 IU/day34% of patients

VERT-NA 1000 mg/day – 100% of patients If <40 nmol/l up to 500 IU/day

HIP 1000 mg/day – 100% of patients If <40 nmol/l up to 500 IU/day30% of patients 70-7944% of patients 80+

Once-A-Week 1000 mg/day – 100% of patients If <30 nmol/l7% of patients

CIO Prevention: 500 mg/day Treatment: 1000 mg/day – 100% of patients

Prevention: NATreatment: 400 IU/day

Strontium 9,10 SOTI Up to 1000 mg/day – to maintain daily calcium intake of 1500 mg

400-800 IU/day depending on baseline levels

TROPOS 500-1000 mg/day. If daily intake <1000 mg/day If <45 nmol/l - 400-800 IU/day

Ibandronate11 BONE 500 mg/day – 100% of patients 400 IU/day

Raloxifene 12 MORE 500 mg/day – 100% of patients 400-600 IU Vit D – 100% of patients

1. Black D et al. Lancet1996; 348: 1535–41. 2. Cummings S et al. JAMA. 1998;280:2077-2082. 3. Pols H et al. Osteoporosis Int 1999; 9:461–468. 4. Reginster J-Y et al, Osteoporosis Int 2000; 11: 83-91. 5. Harris S et al, JAMA 1999; 282: 1344-1352. 6. McClung M et al, N Engl J Med 2001; 344: 333-340. 7. Brown J et al. Calcif Tissue Int 2002; 71: 103-111. 8. Wallach S et al. Calcif Tissue Int 2000; 67:277–285. 9. Meunier P et al. N Engl J Med 2004; 350: 459-468. 10. Reginster J-Y et al. J Clin Endocrinol Metab 2005; 90: 2816-2822. 11. Chesnut C et al. J Bone Minera Res 2004; 19: 1241-1249. 12. Ettinger JAMA. 1999;282:637-645.

.

ConclusionsRDI for calcium:

1000 mg/day for all adults 1300 mg/day for women >50 years & men >70 years

Postmenopausal women are unlikely to receive enough calcium from diet alone

Optimum calcium & vitamin D are key modifiable risk factors for osteoporosis

Calcium + vitamin D is recommended for institutionalised elderly

Vitamin D deficiency is a problem in Australia (World) 25-hydroxyvitamin D assay is indicated in at-risk patients

Doctors should consider recommending calcium and/or vitamin D supplementation to all people taking osteoporosis medication (with exception of calcitriol)5

………..and GOD said let there be light

It is true after all !!!!! BUTLET THERE BE SOME Sun LIGHT ON THE SKIN

-----PLEASE !

Thank you for your attention