2Calcium and vitamin D: who, when, why and how much? Seeva Sivakumaran Senior Staff Specialist Aged Care & Rehabilitation Service The Canberra Hospital
3Agenda Osteoporosis size of the problem 4/6/2017 9:30 AMAgendaOsteoporosis size of the problemCalcium and vitamin D in bone metabolismOsteoporosis prevention and management: the roles of calcium and vitamin DRecommended daily intakesSources of calcium and vitamin DTargeting patients with inadequate intakeConclusions
4The ageing population In developing countries 0 - 15 years 30 % 4/6/2017 9:30 AMThe ageing populationIn developing countriesyears 30 %Over 65 years 5.5 %But changes are expected…
5Definition of osteoporosis 4/6/2017 9:30 AMDefinition 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
6Osteoporotic fracture incidence 4/6/2017 9:30 AMOsteoporotic fracture incidenceWomen755535MenForearmVertebraeHip4,0003,000Incidence per 100,000 person-yearsHip2,000Vertebrae1,000Forearm355575Age (years)Cooper et al. Trends Endocrinol Metab 1992; 3:224
7Trabecular bone normal osteoporotic 4/6/2017 9:30 AMTrabecular bonenormalosteoporoticBone quality is not the only factor …
84/6/2017 9:30 AMSTATISTICS OF THE SILENT EPIDEMIC SOURCE (AIHW) AUSTRALIAN INSTITUDE OF HEALTH AND WELFARE1,014 over 65 died due to accidental falls in 1998,000 hospitalised due to falls25 % 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% wrist50% spinal # do not come to attention!80% patients with osteoporotic # do not receive preventative RX
9OSTEOPOROSIS PREVALENCE 4/6/2017 9:30 AMOSTEOPOROSIS PREVALENCE2002, 1.9 million Australians had osteoporosis.65,514 Australians hospitalised with osteoporotic #= 177 hospitalisations per dayCurrently a # every 8.1 minutes2021 one # every 3.7minutesOsteoporosis:as common as hypertension.more common than hyperlidaemia allergies & the common cold.
10MORBIDITY & MORTALITY 20% with hip # will die wihin 6 months. 4/6/2017 9:30 AMMORBIDITY & MORTALITY20% with hip # will die wihin 6 months.Death rate due to hip # is > all female cancers combined50% patients with hip fracture require long-term nursing care.By in 3 hospital beds will be occupied by women with fractures.
11Pathogenesis of fragility fractures 4/6/2017 9:30 AMPathogenesis of fragility fracturesBone massBone structureBone qualityFall RiskImpact offallSkeletalstrengthFracture riskType of fallEnergy reductionExternal protectionNeuromuscular functionEnvironmental risksAge
13Skeletal roles of calcium & vitamin D Provides structural integrity of skeletonEverybody needs adequate calcium intake, but especially those at risk for osteoporotic fracturesVitamin DBone mineralisationCalcium absorption from small intestineExtracellular calcium homeostasisDeficiency predicts falls in elderly women in nursing homesANZBMS Med J Aust 2005; 182: ; OA & ANZBMS Medicine Today 2005; 6:
14Calcium and osteoporosis 4/6/2017 9:30 AMCalcium and osteoporosis
15The role of calcium Calcium is required on a daily basis Calcium provides strength to the skeleton 1Calcium is the substrate for bone mineralisationSkeletal mass cannot be built or maintained if calcium intake is insufficient or calcium losses are excessive99% of calcium is located in the skeleton 2Bone is the reservoir for calcium and replenishes extracellular fluid (ECF) losses 2Calcium plays a role in muscular, neural and most metabolic processes 21. Heaney RP. Calcif Tissue Int 2002; 70: FAO/WHO expert consultation on human vitamin and mineral requirements, Update March 2002
16Calcium dietary intake Calcium homeostasis Relationship between calcium intake and calcium absorption /excretionCalcium dietary intake700 – 1000 mg/dPTH -Calcium balance (equilibrium) for post-menopausal women reached at intake of ~1000 mg/ day20-35%500 mg/dPlasma & ECFCalcium9.0 – 10.5mg/100mlPTH, 1,25(0H)2DGH, PO4, Sex hormones,CalcitoninPTH, 1,25(0H)2D500 mg/dmg/dPTHFAO/WHO expert consultation on human vitamin and mineral requirements, Update March 2002; HP Kruse, Grundzüge der Osteologie, Springer Verlag 1984450 – 900 mg/d100 – 300 mg/d
17Calcium in osteoporosis treatment Adequate calcium intake is vital1Most 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 fractures31. 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:
18Sub-optimal calcium intake in Australia 87% of women 55 years and older have calcium intakes below the recommended dietary intake (Geelong Osteoporosis Study )11. Pasco J et al. Aust NZ J Med 2000; 30:
19Sub-optimal calcium intake in Australia Mean daily calcium intakeGeelong Osteoporosis Study 1646mg/day among women aged 55-92National Nutrition Survey 2685.6mg/day for females aged 65 and over795.6mg/day for males aged 65 and overRecommendations:NHMRC :1000mg/day for women aged 54 or over800mg/day for males aged 64 or moreANZBMS – OA - Ca & Vit D Forum :1000mg/day for adults1300mg/day for people over 70 years► Gap of 400 – 600 mg Calcium/day1. 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
20Calcium supplementation in Osteoporosis Effect of calcium and vitamin D treatment for 3 years on hip fractures in elderly women3270 mobile elderly women (mean age 84) living in nursing homesCalcium 1.2g/day (in the form of tricalcium phosphate) + Vit D3 800IU/day vs placebo17%* Relative Risk Reduction23%* Relative Risk ReductionITT Analysis% Patients with fractures* p<0.02Chapuy et al. BMJ 1994; 308:
21Calcium supplementation in Osteoporosis Evidence to demonstrate a reduction in fracture risk with increased calcium intake alone78 postmenopausal women completed 4 years of the studyCalcium n=38Mean age : 58+4 yrs9+4 yrs since m’pausePlacebo n=40Mean age : 59+6 yrs10+5 yrs since m’pauseReid I et al American Medical Journal 98:
22Recommended calcium intake 4/6/2017 9:30 AMRecommended calcium intakeAdult men and women mgWomen over 50 yrs mg*Men over 70 yrs mg*Pregnant women mgLactating women mg*Generally not feasible from diet aloneOsteoporosis Australia. Calcium, Vitamin D and Osteoporosis – A Guide for GPs 2nd edn
23Calcium content of common foods 4/6/2017 9:30 AMCalcium content of common foodsOsteoporosis Australia. Calcium, Vitamin D and Osteoporosis – A Guide for GPs 2nd edn
24Who needs more calcium?Risk factors for inadequate dietary calcium intake include:1old agesocial disadvantagemalabsorption due to gastrointestinal diseasecorticosteroid usesex hormone deficiency.Intake < RDI for 75%-87% Australian women2,3Average 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.
25Dietary sources of calcium 4/6/2017 9:30 AMDietary sources of calciumDairy foodsMost readily absorbed form of calciumMain source of calcium in Australian dietsRDI = 3 serves per dayCalcium-enriched soy drinksFish with bones (e.g. tinned salmon)RDI for older people = 1300 mg= 4.5 glasses of milkAustralian 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
27Vitamin 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, fractures160% 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 Australia1. Osteoporosis Australia. Calcium, Vitamin D and Osteoporosis – A Guide for GPs 2nd edn 2. Lips P et al. J Int Med 2006; 260:
28Vitamin D is a Hormone or a Vitamin ? Vitamin D fits the definition of aVitamin and that of a Hormone
29Vitamin 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.VITAMINA substance regularly required by the body in small amounts.The body cannot make vitamins.Must be supplied in diet.
31Classical functions of vitamin D: 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 bonesSupplementary functions:Helps to regulate immune systemRegulates 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
32Non Calcaemic Actions of Vitamin D Reduction to risk of:Osteoporosis (+ calcium supplement).Senile cataract, glucose intolerancePolycystic ovarian syndrome (+ calcium supplement).Reduced lipid peroxidation and increased enzymes protecting oxidationSAD - Seasonal affective disorderRole and association with:Infection control and inflammatory immune functionInfertilityMultiple sclerosis, sjogrens, rheumatoid arthritis, thyroiditis, crohns, and some cancers eg bowel, prostate, breastActivated 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)
33Early symptoms of vitamin D deficiency (Osteomalacia) Muscle pain mainly shoulder /hip girdleRecurrent falls and difficulty transferring in elderlyRecurrent fracturesPoor fracture healingBone painparticularly with bisphosphonatesPremature OAMayo clinic proceedings Dec Plotnikoff GA QuicgleyJMPrabhala 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
34Latitude and Vitamin DLatitude > 45 or higher even summer sun is too weak to produce enough vitamin DCANBERRA southBRISBANE south
35Factors affecting Vitamin D production on skin SeasonGeographic latitudeTime of dayCloud /fogSun screenAgeing skinExcess skin coverWindow glassIndoor life style
36Latitude /Vit D related diseases Multiple sclerosisBreast cancerProstate cancerInsulin dependent diabetesColorectal cancerSchizophreniaHeart diseaseVitamin D may be more important to colon cancerprevention than previously believedJournal of the American Medical Assocition Vol 290 No 22
37Recommended sun exposure (minutes) for moderately fair skin 4/6/2017 9:30 AMRecommended sun exposure (minutes) for moderately fair skinTime (adjust for daylight saving or pigmented skin)Dec-Jan 10:00 or 14:00July-Aug10:00 or 14:0012:00Cairns6-79-127Brisbane15-1911Perth5-620-2815Sydney6-826-2816Adelaide5-725-3819Melbourne32-5225Hobart7-940-4729ANZBMS Med J Aust 2005; 182:
38Control of production of active Vitamin D (calcitriol) Point of regulation of conversion of Vit D to active form is by I hydroxylase in kidneyProduction of Vit D in the skin is determined by latitudeLatitude higher than 30 south and north have insufficient UVB 2-6 months of the year at mid dayLatitude higher than 40 has 6-8 months devoid of adequate UVB
39Daily need of Vitamin DENTIRE 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 METABOLITESIN THE ABSENCE OF ADEQUATE TO SUN EXPOSURE THE BODY DEPENDS ON DIETARY SUPPLY FOR VITAMIN D
40Who 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 antiepilepticDietary supplements Fact Sheet Vit D National Inst. Of Health
41Current 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 sunLack 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
42Vitamin 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 deficiencyCod liver oil contains vitamin A, which may increase fracture riskDosingSupplementation: 1000 IU per dayModerate-severe deficiency: 3000–5000 IU per day for 6–12 weeks then maintenance. Check blood level at 3 monthsCosts approximately 24 cents/day for supplementationANZBMS Med J Aust 2005; 182:
43Pivotal trials – Calcium and Vit D supplementation Alendronate 1-3FIT 1If daily intake <1000 mg/day – 500 mg/day – 82% of patientsIf daily Ca intake <1000 mg/day – 250 IU/day – 82% of patientsFIT 2If daily Ca intake <1000mg/day – 250 IU/day – 82% of patientsFOSIT500 mg/day % of patientsRisedronate 4-8VERT-MN1000 mg/day – 100% of patientsIf <40 nmol/l up to 500 IU/day34% of patientsVERT-NAHIP30% of patients 70-7944% of patients 80+Once-A-WeekIf <30 nmol/l7% of patientsCIOPrevention: 500 mg/dayTreatment: 1000 mg/day – 100% of patientsPrevention: NATreatment: 400 IU/dayStrontium 9,10SOTIUp to 1000 mg/day – to maintain daily calcium intake of 1500 mgIU/day depending on baseline levelsTROPOSmg/day. If daily intake <1000 mg/dayIf <45 nmol/l IU/dayIbandronate11BONE500 mg/day – 100% of patients400 IU/dayRaloxifene 12MOREIU Vit D – 100% of patients1. 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:.
44Conclusions RDI for calcium: 4/6/2017 9:30 AMConclusionsRDI for calcium:1000 mg/day for all adults1300 mg/day for women >50 years & men >70 yearsPostmenopausal women are unlikely to receive enough calcium from diet aloneOptimum calcium & vitamin D are key modifiable risk factors for osteoporosisCalcium + vitamin D is recommended for institutionalised elderlyVitamin D deficiency is a problem in Australia (World)25-hydroxyvitamin D assay is indicated in at-risk patientsDoctors should consider recommending calcium and/or vitamin D supplementation to all people taking osteoporosis medication (with exception of calcitriol)5
45BUT It is true after all !!!!! ………..and GOD said let there be light LET THERE BE SOME Sun LIGHT ON THE SKIN -----PLEASE !