1. DR. MOHAMMED AL DUBAYEE, MD, MHSC, CDE ASSISTANT PROFESSOR, PEDIATRIC ENDOCRINOLOGIST KAMC- RIYADH VTI D BONE AND BEYOND ; WHEN TO SCREEN, WHOM TO TREAT? AND HOW TO TREAT? 1

2. DISCLOSURE 2

3. INTRODUCTION Reports describing significant health risks due vitamin D deficiency is increasing and generate interest in the medical and non-medical field. Number of scientific publications on vitamin D indexed by the PubMed database has been increasing by 15- 20% every year since 2009. Systematic review indicates that an adequate vitamin D status protects against rickets in children (or osteomalacia in adults), osteoporotic fractures, falls, and premature mortality 3

4. Synthesis and Metabolism of Vitamin D ROSEN CJ. N ENGL J MED 2011;364:248-254. 4

5. Vitamin D activity requires at least two elements, metabolism to synthesize the biologically active metabolite 1,25- dihydroxyvitamin D (1,25D) and a receptor protein. Synthesis and Metabolism of Vitamin D 5

6. SKELETAL ACTIONS OF VITAMIN D Vitamin D deficiency results in abnormalities in calcium, phosphorus, and bone metabolism. It cause decrease in the efficiency of intestinal calcium and phosphorus absorption of dietary calcium and phosphorus, resulting in an increase in PTH levels. Vitamin D deficiency also causes muscle weakness, and increase risk of fall. 6

7. VITAMIN D DEFICIENCY 7

8. OSTEOPOROSIS IN ADOLESCENTS ! Gain in bone mass during adolescence. Yearly increase in spine bone mineral content (L2-L4) during adolescence in females (O) and males ( ) JCEM Vol. 85, No. 11 Peak Bone Mass Accrual

9. Vitamin D and Bone Mineral Density at School Age PLoS ONE 7, e40090 (2012). WHY ADOLESCENTS ?

10. PLoS ONE 7, e40090 (2012). WHY ADOLESCENTS ? Association between vitamin D status and physical activity on bone mineral density (BMD).

11. BMD AND FRACTURE RISK Every 1 SD decrease in size-adjusted BMC by DXA, there was an 89% increased risk of fracture. However, the relationship between BMD and fracture risk can varies according to underlying pathology J Bone Miner Res 2006; 21:1489–1495.

12. Synthesis and Metabolism of Vitamin D 12

13. NON-SKELETAL ACTIONS OF VITAMIN D Brain, prostate, breast, and colon tissues, among others, as well as immune cells have a vitamin D receptor and respond to 1,25-dihydroxyvitamin D, the active form of vitamin D. Directly or indirectly, 1,25-dihydroxyvitamin D controls more than 200 genes, including genes responsible for the regulation of cellular proliferation, differentiation, apoptosis, and angiogenesis. 13

14. Cancer: Both prospective and retrospective epidemiologic studies indicate that levels of 25-hydroxyvitamin D below 20 ng per milliliter are associated with a 30 to 50% increased risk of incident colon, prostate, and breast cancer, along with higher mortality from these cancers. 14

15. Autoimmune Diseases: Living at higher latitudes increases the risk of type 1 diabetes, multiple sclerosis, and Crohn’s disease. 15

16. Cardiovascular Disease: Vitamin D deficiency is associated with congestive heart failure and blood levels of inflammatory factors, including C-reactive protein and interleukin-10. 16

17. Vitamin D deficiency is defined as 25(OH)D below 20 ng/ml (50 nmol/liter) Vitamin D insufficiency as a 25(OH)D of 21–29 ng/ml (52.5–72.5 nmol/liter). Evaluation, Treatment, and Prevention of Vitamin D Deficiency: an Endocrine Society Clinical Practice Guideline J Clin Endocrinol Metab, July 2011, 96(7):1911–1930 17

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19. CRITERIA TO DEFINE OPTIMAL 25(OH)D Maximal suppression of PTH Adequate intestinal calcium absorption Fracture prevention 19

20. PTH AND VITAMIN D PTH Causes Ca release from bone (in presence of Vit D) Increases renal reabsorption of Ca Increases renal loss of PO4 Net effect of PTH:  serum Ca  serum PO4 VITAMIN D Increases Ca & PO4 absorption from small bowel Increases renal reabsorption of Ca Increases Ca release from bone (in presence of PTH) Net effect of Vit D:  serum Ca  serum PO4

21. Reduced skin synthesis Decreased bioavailability Increased catabolism Decreased synthesis of 25- hydroxyvitamin D Decreased synthesis of 1,25- dihydroxyvitamin D Increased urinary loss of 25- hydroxyvitamin D Heritable disorders — rickets CAUSES OF VITAMIN D DEFICIENCY 21

22. VTI D BONE AND BEYOND; WHEN TO SCREEN, WHOM TO TREAT? AND HOW TO TREAT? 22

23. WHEN TO SCREEN? Endocrine Society recommend screening for vitamin D deficiency in individuals at risk for deficiency. They do not recommend population screening for vitamin D deficiency in individuals who are not at risk 23

24. POPULATION AT RISK Rickets Osteomalacia Osteoporosis Chronic kidney disease Hepatic failure Malabsorption syndromes Hyperparathyroidism Medications Pregnant and lactating women Older adults with history of falls Older adults with history of nontraumatic fractures Obese children and adults (BMI 30 kg/m2) Granuloma-forming disorders 24

25. Should use Serum circulating 25(OH)D level, measured by a reliable assay, to evaluate vitamin D status in patients who are at risk for vitamin D deficiency. 25

26. Racial differences Black Americans have lower fracture risk and higher bone density than other races. 26 n engl j med 369;21 nejm.org november 21, 2013

27. 27 n engl j med 369;21 nejm.org november 21, 2013

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29. 29 J Clin Endocrinol Metab, July 2011, 96(7):1911–1930

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31. VTI D BONE AND BEYOND; WHEN TO SCREEN, WHOM TO TREAT? AND HOW TO TREAT ? 31

32. Can use either vitamin D2 or vitamin D3 for the treatment and prevention of vitamin D deficiency Vitamin D can be taken on an empty stomach or with a meal. It does not require dietary fat for absorption. Vitamin D given three times a year, once a week, or once a day can be effective in maintaining serum 25(OH)D levels in both children and adults 32

33. VITAMIN D DEFICIENCY IN SAUDI TEENS This is part of the national study on adolescents ‘JEELUNA’ School-based, cross- sectional study which covered all 13 regions of Saudi Arabia Multistage, stratified, cluster random sampling done to select intermediate and secondary male and female schools throughout the country 33 Journal of Adolescent Health 57 (2015) 263e269

34. A total of 12,584 students participated in the study. 4781 had their blood sampled for vitamin D levels and were included in this analysis. 54% were male 53% were in secondary school Corresponding to serum 25-OH vitamin D levels:  39.8% were found to be vitamin D deficient  55.6% had vitamin D insufficiency  Only 4.5% had sufficient vitamin D level Females were significantly more vitamin D deficient than Males (p<.0001) There was no difference between early (=/ 15 years) adolescents VITAMIN D DEFICIENCY IN SAUDI TEENS

35. Regional status of vitamin D levels among adolescents in Saudi Arabia P <.0001 35

36. ARE WE DOING ANY BETTER ? Author Year of publication Population Geographic area in the Kingdome Prevalence of Vit D deficiency(%) Mean Vit D level Mean ±SD nmol/l Ardawi et al 2012Health menJeddah87.8 29.01±16.13 Al-Elq 2012Medical studentsDammam96.0% 26.83 ± 12.60 Mansour et al 2012healthy children aged 4–15 yJeddah79% 32.5± 19.5 Al-Othman et al 2012 healthy Saudi boys and girls aged 6–17 Riyadh All subjects were vitamin D deficient, 12.5± 24.9 Siddiqui et al 2007girls 12-15 yearsJeddah81%2.2-24.0 (range) Abdullah MA et al 2002Adolescents with ricketsRiyadh60%< 25 Al-Jurayyan NA 2002 Hospital based for children and adolescents aged 6-18 y Riyadh All patients diagnosed with rickets < 25 Alyahya et al 2014Adolescents girls, aged 10–18 years, Kuwait 98.7 % <50 nmol/L. Median 25OHD was 19.4 nmol/L (IQR 16.4–23.68), 36

37. THANK YOU

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39. VTI D BONE AND BEYOND; WHEN TO SCREEN, WHOM TO TREAT ? AND HOW TO TREAT? 39

40. RACIAL DIFFERENCES 40

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