J ordan O steoporosis C enter Jordan Hospital

1. Jordan Osteoporosis Center Jordan Hospital Why Vitamin D is important for Bone health? Basel Masri, MD Consultant Rheumatologist Jordanian Osteoporosis Prevention Society Al-Najah University 9 October 2009 Nablus - Palestine

2. Vitamin D • fat soluble prohormone • necessary for bone health, it controls • absorption of calcium from the intestines • and its use in bone mineralization • two important representatives: • Vitamin D2 found in plants considerably less potent than • Vitamin D3 naturally occurring form in humans

3. Sources of Vitamin D (1) • Known as the Sunshine Vitamin • Sunlight Exposure provides 90% of vitamin D for the body’s daily requirement • Vitamin D production is affected by: • season • duration and body-surface of exposure • sunscreen use • and skin pigmentation *Sold in the United States, Canada, Argentina (optional), Brazil, Guatemala, Honduras, Mexico, Philippines (optional), and Venezuela Adapted from Holick MF; Allain TJ, Dhesi J; Webb AR et al; Reid IR et al; Matsuoka LY et al; Holick MF; Lips P; Macleod CC et al; Omdahl JL et al; Chen TC et al; Holick MF et al; Heaney RP; Segal E et al; Webb AR et al; Faulkner H et al; Roche Vitamins Europe Ltd.

4. Sources of Vitamin D (2) • Endogenous production • Ability of skin, liver and kidneys to form and process vitamin D *Sold in the United States, Canada, Argentina (optional), Brazil, Guatemala, Honduras, Mexico, Philippines (optional), and Venezuela Adapted from Holick MF; Allain TJ, Dhesi J; Webb AR et al; Reid IR et al; Matsuoka LY et al; Holick MF; Lips P; Macleod CC et al; Omdahl JL et al; Chen TC et al; Holick MF et al; Heaney RP; Segal E et al; Webb AR et al; Faulkner H et al; Roche Vitamins Europe Ltd.

5. Sources of Vitamin D (3) • Dietary intake 10% only • Minor source of vitamin D, providing 100 IU/day • Vitamin D is rare in foods other than fatty fish, eggs, and supplemented dairy products* • Even vitamin D–fortified dairy products may not contain level indicated on label • Vitamin D can be supplied by multivitamins and supplements • Supplements containing vitamin D alone are not readily available • Patient compliance with supplementation therapy is inconsistent *Sold in the United States, Canada, Argentina (optional), Brazil, Guatemala, Honduras, Mexico, Philippines (optional), and Venezuela Adapted from Holick MF; Allain TJ, Dhesi J; Webb AR et al; Reid IR et al; Matsuoka LY et al; Holick MF; Lips P; Macleod CC et al; Omdahl JL et al; Chen TC et al; Holick MF et al; Heaney RP; Segal E et al; Webb AR et al; Faulkner H et al; Roche Vitamins Europe Ltd.

6. Diseases and Conditions that Vitamin D Helps Prevention • Rickets • Osteomalacia • Osteoporosis • Hyperparathyroism • Internal cancers • Multiple sclerosis

7. Muscle pain, weakness Progression of rheumatoid and osteo-arthritis Type 1 diabetes mellitus in infancy Type 2 diabetes mellitus Body, brain disorders during fetal development Irritable bowel syndrome, Crohn’s disease High blood pressure, heart disease Tuberculosis Other Diseases that UVB /Vitamin D Helps Prevention

8. Reasons for High Prevalence of Vitamin D Inadequacy in Postmenopausal Women • Lack of sunlight exposure • Poor nutrition • Less efficient synthesis of vitamin D in the skin • Lower amount of vitamin D precursor 7-dehydrocholesterol in the skin Adapted from Allain TJ, Dhesi J Gerontology 2003;49:273–278; Holick MF Am J Clin Nutr 1994;60:619–630; Lips P. In: Advances in Nutritional Research, Vol 9. New York: Plenum Press, 1994:151–165; Webb AR et al Am J Clin Nutr 1990;51:1075–1081; Holick MF et al Lancet 1989;2:1104–1105; MacLaughlin J, Holick MF J Clin Invest 1985;76:1536–1538.

9. Deficiency is <10 ng/ml (25 nmol/L) Insufficiency is between 10 and 30 ng/ml (25-75 nmol/L) Below 16 ng/ml (40 nmol/L), circulating 1,25(OH)D levels fall For bone health and other conditions, optimal level is up to 36 ng/ml (90 nmol/L); 40 ng/ml (100 nmol/L) for those over the age of 70 years Levels of Serum 25(OH)D

10. How Much Vitamin D is Required? • Present-day guidelines: • 400 I.U./day for young & middle-aged persons • 600 I.U./day for those around 50-70 years of age • and 800 I.U. for those over the age of 70 years • These guidelines were developed a number of years ago and are based on developing and maintaining strong bones

11. How Much Solar UVB Exposure? • Michael Holick, MD, PhD, Boston University, author of The UV Advantage, now estimates that one needs to expose 25% of the body to midday solar radiation, 2-3 times a week, during summer, to produce the amount of vitamin D considered optimal • This is for light-skinned individuals; darker skinned ones need more exposure

12. Consequences of SubclinicalVitamin D Inadequacy •  Calcium absorption •  PTH •  Bone mineral density Adapted from Parfitt AM et al Am J Clin Nutr 1982;36:1014–1031; Allain TJ, Dhesi J Gerontology 2003;49:273-278; Holick MF Osteoporos Int 1998;8(suppl 2):S24–S29; DeLuca HF Metabolism 1990;39(suppl 1):3–9.

13. Why Vitamin D is important for Osteoporosis Assessment • Epidemiological studies showed worldwide inadequacy in Vitamin D particularly in postmenopausal women • FiJoNOR survey • Others surveys • patients insufficient in Vitamin D show lower improvement with anti-resorptives drugs like bisphosphonates • Evidence suggests that vitamin D inadequacy increases risk of fracture PTH=parathyroid hormone Adapted from Parfitt AM et al Am J Clin Nutr 1982;36:1014–1031; Allain TJ, Dhesi J Gerontology 2003;49:273–278; LeBoff MS et al JAMA 1999;281:1505–1511; Bettica P et al Osteoporos Int 1999;9:226–229; Lips P et al J Clin Endocrinol Metab 2001;86:1212–1221; van der Wielen RPJ et al Lancet 1995;346:207–210.

14. First Jordanian National Osteoporosis RecordFiJoNOR Vitamin D Data FiJoNOR B. Masri, E. Azar, A. Faqih (JOPS)

15. FiJoNOR Population Distribution Total of 821 randomized females Mean age of menopause (48.5) FiJoNOR B. Masri, E. Azar, A. Faqih (JOPS)

16. 33.5% 50.3% 16.2% < 10ng/ml 10-20 ng/ml > 20 ng/ml Deficiency Insufficiency Normal FiJoNOR B. Masri, E. Azar, A. Faqih (JOPS)

17. FiJoNOR B. Masri, E. Azar, A. Faqih (JOPS)

18. FiJoNOR B. Masri, E. Azar, A. Faqih (JOPS)

19. Prevalence of Vitamin D Inadequacy in Postmenopausal Women Treated for Osteoporosis in North America 52.0% N=1536 60 50 35.5% 40 Prevalence, % (± 95% CI) 30 18.2% 20 8.1% 10 1.1% 0 <9 <15 <20 <25 <30 Cutoff points for 25(OH)D concentration (ng/ml) CI=confidence interval Adapted from Holick MF et al J Clin Endocrinol Metab 2005;90:3215–3224.

20. Prevalence of Vitamin D Inadequacy (<30 ng/ml), by Age Group, in Postmenopausal Women Treated for Osteoporosis In an epidemiologic study conducted in North America (N=1536) A high prevalence of vitamin D inadequacy was seen across all age groups 73.3% (n=15) N=1536 80 57.6% (n=245) 53.0% (n=558) 50.7% (n=229) 48.0% (n=488) 60 Prevalence (%) 40 20 0 51–60 61–70 71–80 81–90 >90 Age category p=0.015 for test of trend Adapted from Holick MF et al. Poster presented at ASBMR, October 1–5, 2004, Seattle, WA, USA.

21. Prevalence of Vitamin D Inadequacy (<30 ng/ml), by Region, in Postmenopausal Women with Osteoporosis In a cross-sectional observational international study A high prevalence of vitamin D inadequacy was seen across all geographic regions 81.8% 90 N=2589 71.4% 80 63.9% 70 60.3% 53.4% 57.7% 60 50 Prevalence (%) 40 30 20 10 0 All Australia LatinAmerica Asia Middle East Europe Regions Adapted from Lips P et al. Poster presented at ASBMR, September 23–27, 2005, Nashville, TN, USA.

22. Vitamin D Supplementation Decreases Fracture Risk

23. The neglected role of „Muscle“ in the pathogenesis of Osteoporosis Muscle Bone Density Falls Osteoporosis (Immobil.-induced Opo.) Fracture

24. Active Vitamin D reduces the risk of osteoporotic fractures by a dual effect Vitamin D + Muscle + Bone Density Falls Osteoporosis Fractures

25. In a clinical studyVitamin D Supplementation Decreases Fracture Risk • Five-year randomized, double-blind, controlled trial • N=2686 • Age 65–85 years • Vitamin D = 100,000 IU once every four months (equivalent to 800 IU/day) • Men and women living in the community 1.2 p=0.02 1.0 –33% 0.8 Fracture relative risk(hip, wrist, forearm, spine) 0.6 0.4 0.2 0.0 Untreated (n=1341) Treated (n=1345) Adapted from Trivedi D et al BMJ 2003;326:469.

26. Effect of Vitamin D and Calcium Supplementation on Risk of Falling • 122 women • Age: 63–99 years • Randomized, double-blind, controlled trial: • Calcium 1200 mg/day • Calcium 1200 mg/day + vitamin D 800 IU/day • 12-week duration • Mean serum 25(OH)D 12 ng/ml at baseline • Women living in long-term care units Reduction in falls 1.2 p=0.01 1.0 0.8 –49% 0.6 Fall risk 0.4 0.2 0.0 Calcium only (n=44) Calcium + vitamin D (n=45) Adapted from Bischoff HA et al J Bone Miner Res 2003;18:343–351.

27. Summary I • Vitamin D inadequacy is widespread in postmenopausal women • Postmenopausal women have difficulty getting enough Vitamin D: • Formation and processing of vitamin D may be impaired • Exposure to sunlight may be limited • Dietary sources provide little vitamin D • Patient compliance with vitamin D supplementation is inconsistent

28. Summary II • Vitamin D is essential for calcium absorption. Adequate calcium absorption prevents secondary hyperparathyroidism and limits bone resorption • Vitamin D supplementation has been shown to reduce the risk of fracture and falls and improves lower extremity function in the elderly • Vitamin optimize antiresorptive drugs efficacy specially Bisphosphonates