1. CLINICAL OVERVIEW VITAMIN D & Calcium Dr.Seeva Sivakumaran
Senior Staff Specialist
The Canberra Hospital

2. Calcium and vitamin D: who, when, why and how much?
Seeva Sivakumaran Senior Staff Specialist Aged Care & Rehabilitation Service The Canberra Hospital

3. Agenda Osteoporosis size of the problem
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Agenda
Osteoporosis size of the problem
Calcium and vitamin D in bone metabolism
Osteoporosis 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

4. The ageing population In developing countries 0 - 15 years 30 %
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The ageing population
In developing countries
years 30 %
Over 65 years 5.5 %
But changes are expected…

5. Definition of osteoporosis
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Definition of osteoporosis
“…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.”
World Health Organization (WHO), 1994

6. Osteoporotic fracture incidence
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Osteoporotic fracture incidence
Women 75 55 35
Men
Forearm
Vertebrae
Hip
4,000
3,000
Incidence per 100,000 person-years
Hip
2,000
Vertebrae
1,000
Forearm 35 55 75
Age (years)
Cooper et al. Trends Endocrinol Metab 1992; 3:224

7. Trabecular bone normal osteoporotic
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Trabecular bone
normal
osteoporotic
Bone quality is not the only factor …

8. 4/6/2017 9:30 AM
STATISTICS OF THE SILENT EPIDEMIC SOURCE (AIHW) AUSTRALIAN INSTITUDE OF HEALTH AND WELFARE
1,014 over 65 died due to accidental falls in 1998
,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

9. OSTEOPOROSIS PREVALENCE
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OSTEOPOROSIS PREVALENCE
2002, 1.9 million Australians had osteoporosis.
65,514 Australians hospitalised with osteoporotic #
= 177 hospitalisations per day
Currently a # every 8.1 minutes
2021 one # every 3.7minutes
Osteoporosis:
as common as hypertension.
more common than hyperlidaemia allergies & the common cold.

10. MORBIDITY & MORTALITY 20% with hip # will die wihin 6 months.
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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 in 3 hospital beds will be occupied by women with fractures.

11. Pathogenesis of fragility fractures
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Pathogenesis of fragility fractures
Bone mass
Bone structure
Bone quality
Fall Risk
Impact of
fall
Skeletal
strength
Fracture risk
Type of fall
Energy reduction
External protection
Neuromuscular function
Environmental risks
Age

12. Calcium and vitamin D in bone metabolism

13. Skeletal roles of calcium & vitamin D
Provides structural integrity of skeleton
Everybody needs adequate calcium intake, but especially those at risk for osteoporotic fractures
Vitamin D
Bone mineralisation
Calcium absorption from small intestine
Extracellular calcium homeostasis
Deficiency predicts falls in elderly women in nursing homes
ANZBMS Med J Aust 2005; 182: ; OA & ANZBMS Medicine Today 2005; 6:

14. Calcium and osteoporosis
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Calcium and osteoporosis

15. 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: FAO/WHO expert consultation on human vitamin and mineral requirements, Update March 2002

16. Calcium dietary intake
Calcium homeostasis Relationship between calcium intake and calcium absorption /excretion
Calcium dietary intake
700 – 1000 mg/d
PTH -
Calcium balance (equilibrium) for post-menopausal women reached at intake of ~1000 mg/ day
20-35%
500 mg/d
Plasma & ECF
Calcium
9.0 – 10.5
mg/100ml
PTH, 1,25(0H)2D
GH, PO4, Sex hormones,
Calcitonin
PTH, 1,25(0H)2D
500 mg/d
mg/d
PTH
FAO/WHO expert consultation on human vitamin and mineral requirements, Update March 2002; HP Kruse, Grundzüge der Osteologie, Springer Verlag 1984
450 – 900 mg/d
100 – 300 mg/d

17. 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:

18. 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:

19. 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 :
1000mg/day for women aged 54 or over
800mg/day for males aged 64 or more
ANZBMS – OA - Ca & Vit D Forum :
1000mg/day for adults
1300mg/day for people over 70 years
► Gap of 400 – 600 mg Calcium/day
1. Pasco J et al. Aust NZ J Med 2000; 30: National Nutrition Survey – ABS National Health and Medical Research Council. Australian Government Publishing Service, Calcium, Vitamin D and Osteoporosis – A guide for GPs – Osteoporosis Australia – In press

20. Calcium supplementation in Osteoporosis
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
17%* Relative Risk Reduction
23%* Relative Risk Reduction
ITT Analysis
% Patients with fractures
* p<0.02
Chapuy et al. BMJ 1994; 308:

21. Calcium supplementation in Osteoporosis
Evidence to demonstrate a reduction in fracture risk with increased calcium intake alone
78 postmenopausal women completed 4 years of the study
Calcium n=38
Mean age : 58+4 yrs
9+4 yrs since m’pause
Placebo n=40
Mean age : 59+6 yrs
10+5 yrs since m’pause
Reid I et al American Medical Journal 98:

22. Recommended calcium intake
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Recommended calcium intake
Adult men and women mg
Women over 50 yrs mg*
Men over 70 yrs mg*
Pregnant women mg
Lactating women mg
*Generally not feasible from diet alone
Osteoporosis Australia. Calcium, Vitamin D and Osteoporosis – A Guide for GPs 2nd edn

23. Calcium content of common foods
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Calcium content of common foods
Osteoporosis Australia. Calcium, Vitamin D and Osteoporosis – A Guide for GPs 2nd edn

24. Who needs more calcium?
Risk factors for inadequate dietary calcium intake include:1
old age
social disadvantage
malabsorption due to gastrointestinal disease
corticosteroid use
sex 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, yoghurt4
1. 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.

25. Dietary sources of calcium
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Dietary sources of calcium
Dairy foods
Most readily absorbed form of calcium
Main source of calcium in Australian diets
RDI = 3 serves per day
Calcium-enriched soy drinks
Fish with bones (e.g. tinned salmon)
RDI for older people = 1300 mg
= 4.5 glasses of milk
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

26. Vitamin D and osteoporosis

27. Vitamin D deficiency is common
Vitamin 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 edn 2. Lips P et al. J Int Med 2006; 260:

28. Vitamin D is a Hormone or a Vitamin ?
Vitamin D fits the definition of a
Vitamin and that of a Hormone

29. Vitamin D : A Hormone & A Vitamin
A 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.
VITAMIN
A substance regularly required by the body in small amounts.
The body cannot make vitamins.
Must be supplied in diet.

31. Classical functions of vitamin D:
Regulation of calcium homeostasis and bone mineralization
Promotes intestinal absorption of calcium
Promotes resorption of ca++ in kidneys
Mobilizes 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 proliferation
Works synergistically with vitamin A to induce certain cancer cells to differentiate in to normal cells and to inhibit cancer cell proliferation

32. Non Calcaemic Actions 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 disorder
Role 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)

33. Early symptoms of vitamin D deficiency (Osteomalacia)
Muscle pain mainly shoulder /hip girdle
Recurrent falls and difficulty transferring in elderly
Recurrent fractures
Poor fracture healing
Bone pain
particularly with bisphosphonates
Premature OA
Mayo clinic proceedings Dec Plotnikoff GA QuicgleyJM
Prabhala A Arch Intern Med 2000
Al Faraj et al Spine 2003
PfeiferM et al J Bone Miner 2000
M.Hollick Vit D Millinium Perspective J Cell Biochem 2003

34. Latitude and Vitamin D
Latitude > 45 or higher even summer sun is too weak to produce enough vitamin D
CANBERRA south
BRISBANE south

35. Factors affecting Vitamin D production on skin
Season
Geographic latitude
Time of day
Cloud /fog
Sun screen
Ageing skin
Excess skin cover
Window glass
Indoor life style

36. Latitude /Vit D related diseases
Multiple sclerosis
Breast cancer
Prostate cancer
Insulin dependent diabetes
Colorectal cancer
Schizophrenia
Heart disease
Vitamin D may be more important to colon cancer
prevention than previously believed
Journal of the American Medical Assocition Vol 290 No 22

37. Recommended sun exposure (minutes) for moderately fair skin
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Recommended sun exposure (minutes) for moderately fair skin
Time (adjust for daylight saving or pigmented skin)
Dec-Jan 10:00 or 14:00
July-Aug
10:00 or 14:00
12:00
Cairns
6-7
9-12 7
Brisbane
15-19 11
Perth
5-6
20-28 15
Sydney
6-8
26-28 16
Adelaide
5-7
25-38 19
Melbourne
32-52 25
Hobart
7-9
40-47 29
ANZBMS Med J Aust 2005; 182:

38. Control of production of active Vitamin D (calcitriol)
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

39. Daily need of Vitamin D
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

40. Who may need extra Vitamin D
Infants who are exclusively Breast Fed
Older adults
Persons with limited sun exposure
People with pigmented skin
Patients with malabsorption
Patients on prednisolone & thyroid supplements and those on antiepileptic
Dietary supplements Fact Sheet Vit D National Inst. Of Health

41. Current Problems with Vitamin D administration
Recommended Daily Allowance (RDA) is probably set too low
Lab normal range is set too low
Poor dietary intake -- Diet poor substitute for sun
Lack of food fortification
High Dose Vit D3 Not available in Australia
Calcitriol available on PBS but not appropriate
Many patients on bisphosphonates with no Vit D or Ca
Caution – 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

42. Vitamin D supplementation
Use formulations with sufficient dose:
Ostelin (ergocalciferol 25 µg = D IU)
Ostevit D, Blackmores Vitamin D (cholecalciferol = D 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 risk
Dosing
Supplementation: 1000 IU per day
Moderate-severe deficiency: 3000–5000 IU per day for 6–12 weeks then maintenance. Check blood level at 3 months
Costs approximately 24 cents/day for supplementation
ANZBMS Med J Aust 2005; 182:

43. Pivotal trials – Calcium and Vit D supplementation
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 Ca intake <1000mg/day – 250 IU/day – 82% of patients
FOSIT
500 mg/day % of patients
Risedronate 4-8
VERT-MN
1000 mg/day – 100% of patients
If <40 nmol/l up to 500 IU/day
34% of patients
VERT-NA
HIP
30% of patients 70-79
44% of patients 80+
Once-A-Week
If <30 nmol/l
7% of patients
CIO
Prevention: 500 mg/day
Treatment: 1000 mg/day – 100% of patients
Prevention: NA
Treatment: 400 IU/day
Strontium 9,10
SOTI
Up to 1000 mg/day – to maintain daily calcium intake of 1500 mg
IU/day depending on baseline levels
TROPOS
mg/day. If daily intake <1000 mg/day
If <45 nmol/l IU/day
Ibandronate11
BONE
500 mg/day – 100% of patients
400 IU/day
Raloxifene 12
MORE
IU Vit D – 100% of patients
1. Black D et al. Lancet1996; 348: 1535– Cummings S et al. JAMA. 1998;280: Pols H et al. Osteoporosis Int 1999; 9:461– Reginster J-Y et al, Osteoporosis Int 2000; 11: Harris S et al, JAMA 1999; 282: McClung M et al, N Engl J Med 2001; 344: Brown J et al. Calcif Tissue Int 2002; 71: Wallach S et al. Calcif Tissue Int 2000; 67:277– Meunier P et al. N Engl J Med 2004; 350: Reginster J-Y et al. J Clin Endocrinol Metab 2005; 90: Chesnut C et al. J Bone Minera Res 2004; 19: Ettinger JAMA. 1999;282: .

44. Conclusions RDI for calcium:
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Conclusions
RDI 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

45. BUT It is true after all !!!!! ………..and GOD said let there be light
LET THERE BE SOME Sun LIGHT ON THE SKIN -----PLEASE !

46. 4/6/2017 9:30 AM
Seasonal Variation

50. Thank you for your attention
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Thank you for your attention
Osteoporosis ,Calcium & Vitamin D
Dr.S Sivakumaran
The Canberra Hospital