Seminar 15-01-2009 - osteoporose, calcium en vitamine d

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  • 1. Osteoporose, Calcium en Vitamine D Dr. JPW van den Bergh, internist-endocrinoloog 15 april 2009
  • 2. Vitamine D: productie en effect ProD3=provitamin D3; PreD3=previtamin D3 Holick MF Osteoporos Int 1998;8(suppl 2):S24S29. Huid Lever Nieren Diet Vitamine D3 Vitamine D2 Darm Bot ProD3 PreD3 Vitamine D3 25(OH)D 1,25(OH)2D PTH (+) UVBZon (+) Laag PO4 2-Toename calcium en fosfaat absorptie Mobiliseren van calcium voorrraden Reguleren serum calcium en fosfaat Metabole werking Gezond Bot Neuromusculaire functie
  • 3. Vitamine D2 - Ergocalciferol Vitamine D2 Wordt gevonden in planten In sommige voedingsmiddelen en multivitaminen (vooral US) Biologisch inert Conversie (OH) in lever en nieren naar actieve vorm D2 is veel minder sterk dan D Parfitt AM et al Am J Clin Nutr 1982;36:10141031;Lips P Endocr Rev 2001;22:477501; Holick MF Osteoporos Int 1998;8(suppl 2): S24S29; Holick MF et al. In: Bone and Mineral Research, Vol 7. Amsterdam: Elsevier, 1990:313366 CH3 HO CH2 CH3 H H3C CH3 CH3 H
  • 4. Vitamine D3 - Colecalciferol Vitamine D3 Gevormd door activatie met ultraviolet licht op vitamine D precursors in de huid Sommige voedingsmiddelen Biologisch inert Conversie (OH) in lever en nieren naar actieve vorm Parfitt AM et al Am J Clin Nutr 1982;36:10141031; Lips P Endocr Rev 2001;22:477501 HO CH2 CH3 H H3C CH3 CH3 H
  • 5. 1.25 dihydroxy-vitamine D - Calcitriol (1,25[OH]2D) Gevormd door achtereenvolgende hydroxyleringen in lever en nieren Biologisch actieve vorm 1000 keer meer actief dan vitamine D3 of D2 Teveel kan leiden tot toxiciteit: hypercalcimie en hypercalcirie Parfitt AM et al Am J Clin Nutr 1982;36:10141031; Guyton AC and Hall JE. In: Textbook of Medical Physiology, 10th ed. Philadelphia, Pa: WB Saunders, 2000:899915 HO CH2 CH3 H H3C CH3 CH3 H OH OH
  • 6. 1,25 (OH)2 vit D maintains calcium homeostasis Thus vit D deficiency results in elevated parathyroid hormone Rickets in children Osteomalacia in adults Osteoporosis Calcium en Phosphate balance
  • 7. 262 postmenopausal women aged 40-87 yrs Nordin et al 2004 Am J Clin Nutr Relation calcium absorption and 1,25(OH)2 vitaminD
  • 8. Nordin et al 2004 Am J Clin Nutr Calcium absorption, effect of age
  • 9. What this study adds Healthy older women randomised to calcium supplementation showed increased rates of myocardial infarction This effect could outweigh any benefits on bone from calcium supplements Bolland et al BMJ 2008: Conclusion Calcium supplementation in healthy postmenopausal women is associated with upward trends in cardiovascular events rates Vascular events in healthy older women receiving calcium supplementation: randomised controlled trial Substitution 1000 mg Ca +Substitution 1000 mg Ca + Dietary intake 860 mg CaDietary intake 860 mg Ca
  • 10. Vascular events & calcium supplementation Letters to BMJ Calcium supplementation: Results may not be generalisable Confounders (non-adjusted) Calcium group had more smokers (RR 1.3) Calcium group had history of ischaemic heart disease (RR 1.1) Previous treated dislipideamia (RR1.2) Calcium group had history of stroke (RR1.6) Drop-outs Calcium & control group had high drop out rates (46% & 40%) Intention to treat analysis Was not mentioned in article
  • 11. Calcium/vitamin D supplementation and cardiovascular events (WHI) Randomized 36,282 postmenopausal women 50 to 79 years of age calcium carbonate 1000 mg / vitamin D 400 IU or placebo. 499 vs 475 women had myocardial infarction or coronary heart disease death: HR 1.04 (95% CI 0.92 - 1.18) 362 & 377 women had a stroke: HR 0.95 (95% CI 0.82 - 1.10) CONCLUSIONS: Calcium/vitamin D supplementation neither increased nor decreased coronary or cerebrovascular risk in generally healthy postmenopausal women over a 7-year use period. Hsia et al Circulation 2007
  • 12. Calcium, vitamine D en het skelet
  • 13. Antifractuur effect vitamine D en calcium De rol van calcium als monotherapie De rol van therapietrouw Tang BM, Eslick GD, Nowson C, Smith C, Bensoussan A. Use of calcium or calcium in combination with vitamin D supplementation to prevent fractures and bone loss in people aged 50 years and older: a meta- analysis. Lancet 2007; 370: 657-666 Effecten bij mensen ouder dan 50 jaar
  • 14. Tang BM, et al. The Lancet 2007
  • 15. Tang BM, et al. The Lancet 2007
  • 16. Overall therapie effect Tang BM, et al. The Lancet 2007
  • 17. Het effect van calcium t.o.v. calcium en vitamine D Tang BM, et al. The Lancet 2007
  • 18. Het effect van therapietrouw Tang BM, et al. The Lancet 2007
  • 19. Conclusie meta-analyse 63.897; 29 RCTs 52.625; 17 RCTs fractuur 12% 0.88, 95% CI (0.83-0.95) Hoge compliance rate 24% meer effect < 1200mg contra 1200mg calcium (0.80 vs. 0.90; p= 0.006) < 700-800IU contra 800IU vit. D (0.84 vs. 0.87; p= 0.03) Tang BM, Eslick GD, Nowson C, Smith C, Bensoussan A. Use of calcium or calcium in combination with vitamin D supplementation to prevent fractures and bone loss in people aged 50 years and older: a meta- analysis. Lancet 2007; 370: 657-666
  • 20. The treatment effect was greater in people who were institutionalised than in those living in the community (RR 076 vs 094; p=0003) Age was an important determinant of treatment efficacy. Risk reduction was less in people aged 5070 years than in those who were older than 70 years Tang et al, the Lancet 2007
  • 21. Calcium and vitamin D versus placebo for prevention of osteoporotic fractures. Analysis excludes two studies of very old, frail women living in institutions. Correspondence Calcium and vitamin D for prevention of osteoporotic fractures Bo Freyschuss, et al. The Lancet 2007;
  • 22. 6 RCTs 45.000 Vit. D + calcium effect 4 RCTs 8083 Vit. D geen effect De rol van calcium en heupfracturen Boonen S et al. Need for additional calcium to reduce the risk of hip fracture with vitamin d supplementation: evidence from a comparative metaanalysis of randomized controlled trials.J Clin Endocrinol Metab. 2007; 92: 1415-23. 0.75 (95% CI 0.58, 0.96)
  • 23. Bischoff-Ferrari HA, Willett WC, Wong JB, Giovannucci E, Dietrich T, Dawson- Hughes B. Fracture prevention with vitamin D supplementation: a meta-analysis of randomized controlled trials. JAMA 2005; 293: 2257-2264.
  • 24. Vitamine D deficintie bij osteoporose patinten
  • 25. Vitamine D tekort Definitie Geen consensus 25(OH)D concentratie