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Dr.Seeva Sivakumaran Senior Staff Specialist The Canberra Hospital 22-08-2007

CLINICAL OVERVIEW VITAMIN D & Calcium. Dr.Seeva Sivakumaran Senior Staff Specialist The Canberra Hospital 22-08-2007. Calcium and vitamin D: who, when, why and how much?. Seeva Sivakumaran Senior Staff Specialist Aged Care & Rehabilitation Service The Canberra Hospital. Agenda.

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Dr.Seeva Sivakumaran Senior Staff Specialist The Canberra Hospital 22-08-2007

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  1. CLINICAL OVERVIEW VITAMIN D & Calcium Dr.Seeva Sivakumaran Senior Staff Specialist The Canberra Hospital 22-08-2007

  2. Calcium and vitamin D:who, when, why and how much? Seeva Sivakumaran Senior Staff SpecialistAged Care & Rehabilitation ServiceThe Canberra Hospital

  3. 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 % Over 65 years 5.5 % But changes are expected…

  5. 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. Men Hip Vertebrae Forearm 35 55 75 Osteoporotic fracture incidence Women 4,000 3,000 Hip Incidence per 100,000 person-years 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 Bone quality is not the only factor …

  8. STATISTICS OF THE SILENT EPIDEMICSOURCE (AIHW) AUSTRALIAN INSTITUDE OF HEALTH AND WELFARE • 1,014 over 65 died due to accidental falls in 1998 • 1998 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

  9. OSTEOPOROSIS PREVALENCE • 2002, 1.9 million Australians had osteoporosis. • 65,514 Australians hospitalised with osteoporotic # • 2002 = 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. • 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.

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

  12. Calcium and vitamin D in bone metabolism

  13. Calcium 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 Skeletal roles of calcium & vitamin D ANZBMS Med J Aust 2005; 182: 281-285; OA & ANZBMS Medicine Today 2005; 6: 43-50.

  14. Calcium and osteoporosis

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

  16. 500 mg/d Calcium homeostasisRelationship 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% Plasma & ECF Calcium 9.0 – 10.5 mg/100ml GH, PO4, Sex hormones, Calcitonin PTH, 1,25(0H)2D PTH, 1,25(0H)2D 500 mg/d 50-250 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 PNet al, Med J Aust2002;176:S1-S15; 3. Chapuy MCet al, N Engl J Med 1992;327:1637-42.

  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: 21-27.

  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 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 ► Gap of 400 – 600 mg Calcium/day 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

  20. 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 17%* Relative Risk Reduction 23%* Relative Risk Reduction ITT Analysis % Patients with fractures * p<0.02 Chapuy et al. BMJ 1994; 308:1081-1082

  21. Evidence to demonstrate a reduction in fracture risk with increased calcium intake alone Calcium supplementation in Osteoporosis 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. 1995 American Medical Journal 98: 331-335

  22. Adult men and women 1000 mg Women over 50 yrs 1300 mg* Men over 70 yrs 1300 mg* Pregnant women 1100 mg Lactating women 1200 mg Recommended calcium intake *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 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 PNet 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 RDI for older people = 1300 mg • 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) =4.5 glasses of milk Australian Food and Nutrition Monitoring Unit 2001; OA & ANZBMS Medicine Today2005;6:43-50; Sambrook PNet 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 edn2. Lips P et al.J Int Med 2006; 260:245-254.

  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 HORMONE • 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.

  30. 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

  31. 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)

  32. 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 2003 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

  33. Latitudeand Vitamin D • Latitude > 45 or higher even summer sun is too weak to produce enough vitamin D • CANBERRA -35.27 south • BRISBANE 27 south

  34. 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

  35. 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

  36. Recommended sun exposure (minutes) for moderately fair skin ANZBMS Med J Aust 2005; 182: 281-285.

  37. 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

  38. 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

  39. 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

  40. 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

  41. Vitamin D supplementation • Use 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 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: 281-285.

  42. Pivotal trials – Calcium and Vit D supplementation 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. .

  43. 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

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

  45. Seasonal Variation

  46. Thank you for your attention Osteoporosis ,Calcium & Vitamin D Dr.S Sivakumaran The Canberra Hospital 22-08-2007

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