Vitamin D and bone health in a sub-sample of elderly patients from the TUDA 1 Cohort Study.

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1 Vitamin D and bone health in a sub-sample of elderly patients from the TUDA 1 Cohort Study. L Hoey 2, L McAnena 2, JMW Wallace 2, A Molloy 3, C Cunningham 4 and H McNulty 2 1 Trinity, Ulster, Department of Agriculture Study 2 Northern Ireland Centre for Food and Health (NICHE), University of Ulster, Coleraine. 3 School of Biochemistry and Immunology, Trinity College Dublin, Ireland. 4 The Mercers Institute for Research on Ageing (MIRA), St James's Hospital, Dublin.

2 Bone health Osteoporosis is an increasingly common degenerative condition Bone health can be influenced by a number of nutritional factors including vitamin D (25(OH)D)

3 Vitamin D Fat soluble vitamin found in two forms Vitamin D 2 / ergocalciferol synthesised in plants Vitamin D 3 / cholecalciferol synthesised in animals Two main forms in human body 25(OH)D 3 (status measure) 1,25(OH) 2 D 3 / calcitrol (active form) Primary source is dermal bio-synthesis following UVB exposure Geographical location and weather are a major determinant of the rate of synthesis 1 1 Laird et al. (2010) Nutrients 2,

4 Vitamin D Few dietary sources: - Oily fish - Cod liver oil - Eggs - Liver - Fortified products Margarine Breakfast cereals.

5 Measurement of vitamin D in blood: sufficient and deficient status <25 nmol/l Deficient nmol/l Insufficient >50 nmol/l Sufficient Irish female patients >65y 2-25% deficient - 75% insufficient Irish women >65y 3-9% deficient - 44% insufficient 2 DeLappe et al (2006) European Journal of Clinical Nutrition 60, Lardner et al (2011) Irish Journal of Medical Science 180,

6 Aim To investigate in elderly patients the relationships between vitamin D and bone health measured by: BMD (gold standard) Biomarkers of bone turnover in blood

7 Methodology Cognitive cohort n=2000 TUDA cohort n=6000 (>60y) Hypertensive cohort n=2000 Osteoporotic cohort n=2000 Questionnaires Demographics Health & Lifestyle FFQ Blood samples Vitamin D PTH Biomarkers of bone turnover Additional measures Height, weight DXA bone scan 647 subjects were available for analysis

8 Participant characteristics Total n=647 Males n=295 Females n=352 P-value* General characteristics Age (y) 67.7 ± ± ± BMI (kg/m²) 29.9 (26.9, 33.5) 29.6 (27.1, 32.5) 30.2 (26.6, 34.6) DXA BMD (g/cm 2 ) Vertebral ± ± ± <0.001 Total hip ± ± ± <0.001 Femoral neck ± ± ± <0.001 Mean ± SD, median (IQR) *Independent t-test on log transformed data where applicable

9 Blood measurements Total n=647 Males n=295 Females n=352 P-value* Vitamin D (nmol/l) 42.1 (28.1, 55.9) 45.5 (33.2, 58.6) 38.2 (25.2, 53.6) <0.001 PTH (pg/ml) 42.9 (33.1, 57.2) 40.8 (32.3, 53.3) 44.6 (34.0, 59.5) Biomarkers of bone formation OC (ng/ml) 14.0 (10.7, 19.1) 12.6 (9.8, 16.7) 15.7 (11.6, 21.2) <0.001 BAP (µg/l) 15.7 (12.7, 20.2) 14.4 (12.1, 18.0) 17.1 (13.7, 21.2) <0.001 Biomarkers of bone resorption CTX (ng/ml) 0.26 (0.20, 0.35) 0.25 (0.19, 0.32) 0.28 (0.21, 0.39) <0.001 TRAP (U/L) 2.98 (2.42, 3.60) 2.80 (2.29, 3.50) 3.10 (2.48, 3.70) Median (IQR) *Independent t-test on log transformed data where applicable PTH, parathyroid hormone; OC, osteocalcin and BAP, bone-specific alkaline phosphatase; CTX, crosslaps and TRAP, BoneTRAP

10 Prevalence of bone disease

11 Vitamin D status

12 Monthly vitamin D concentration 50nmol/l 25nmol/l

13 Correlations between vitamin D and BMD at 3 sites in women Partial correlations controlling for age and BMI

14 Correlations between BMD (total hip) and blood measures of bone formation in women Partial correlations controlling for age and BMI

15 Correlations between BMD (total hip) and blood measures of bone resorption in women Partial correlations controlling for age and BMI

16 Biomarkers of bone health in participants with normal vs low BMD General characteristics Normal BMD (n=231) Low BMD (n=398) P value* Age (y) 66.1 (63.3, 70.2) 67.2 (63.6, 71.4) Males (%) BMI (kg/m 2 ) 31.2 (28.3, 34.3) 29.2 (26.4, 32.7) <0.001 Blood measurements 25(OH)D (nmol/l) 44.2 (31.1, 57.8) 41.2 (27.2, 54.6) PTH (pg/ml) 41.2 (31.7, 52.7) 43.2 (33.9, 59.1) Biomarkers of bone formation OC (ng/ml) 13.1 (9.7, 17.8) 14.5 (10.9, 19.3) BAP (ug/l) 15.2 (12.4, 19.1) 16.2 (12.7, 20.7) Biomarkers of bone resorption CTX (ng/ml) 0.25 (0.19, 0.31) 0.28 (0.21, 0.38) TRAP (U/L) 2.80 (2.24, 3.43) 3.04 (2.44, 3.77) <0.001 Normal BMD, a T-score of -0.9 or higher. Low BMD (i.e. Osteopenic/osteoporotic), a T-score of -1.0 or lower *Independent sample t-test

17 Summary of results Vitamin D deficiency/insufficiency and poor bone health are common in the elderly, especially in women. Although novel biomarkers of bone turnover in blood were strongly associated with BMD, they were not related to vitamin D status. Further work: - Re-examine these relationships taking into account important confounders and the role of genetic factors.

18 Acknowledgements Funders: Irish Department of Agriculture with co-funding from the Northern Ireland Department for Employment and Learning through its Strengthening the all-island Research Base initiative. Original TUDA Investigators (Research and Clinical) UU Prof Sean Strain Prof Helene McNulty Dr Mary Ward Dr Julie Wallace Dr Geraldine Horigan Dr Liadhan McAnena Dr Julie Sittlington Dr Mary McCann Dr Catherine Hughes Mr Adrian McCann Mrs Kim Martin Mrs Ingrid Love Mr Eamon Laird Dr Paula Tighe Ms Shauna Harte TUDA Team TCD/SJH Prof John Scott Dr Anne Molloy Dr Conal Cunningham Dr Miriam Casey Dr Kevin McCarroll Mrs Sinead McNiffe Ms Helen Toohey Ms Clare O Donovan Mr Gerry Cox Ms Regina Dempsey Ms Karen Creevey Ms Tracey Claxton And a thank you to all the participants!

19 Thank-you

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