Simon Hsu1, David K Prince1, Kayleen Williams2, Norrina B Allen3, Gregory L Burke4, Andrew N Hoofnagle5, Xiaohui Li6, Kiang J Liu7, Robyn L McClelland2, Erin D Michos8,9, Bruce M Psaty10, Steven J Shea11,12, Kenneth M Rice2, Jerome I Rotter6, David Siscovick13, Russell P Tracy14, Karol E Watson15, Bryan R Kestenbaum1, Ian H de Boer1. 1. Division of Nephrology and Kidney Research Institute, Department of Medicine, University of Washington, Seattle, WA, USA. 2. Department of Biostatistics, University of Washington, Seattle, WA, USA. 3. Department of Internal Medicine, Northwestern University, Chicago, IL, USA. 4. Division of Public Health Sciences Wake Forest School of Medicine, Winston-Salem, NC, USA. 5. Department of Laboratory Medicine, University of Washington, Seattle, WA, USA. 6. The Institute for Translational Genomics and Population Sciences, Department of Pediatrics, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA, USA. 7. Department of Preventive Medicine, Northwestern University, Chicago, IL, USA. 8. Division of Cardiology, Department of Medicine, Johns Hopkins University, Baltimore, MD, USA. 9. Department of Epidemiology and the Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA. 10. Cardiovascular Health Research Unit, Departments of Medicine, Epidemiology, and Health Services, University of Washington, Seattle, WA, USA. 11. Department of Medicine, Columbia University College of Physicians and Surgeons, New York, NY, USA. 12. Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY, USA. 13. New York Academy of Medicine, New York, NY, USA. 14. Department of Biochemistry, University of Vermont, Burlington, VT, USA. 15. Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
Abstract
BACKGROUND: Different 25-hydroxyvitamin D [25(OH)D] thresholds for treatment with vitamin D supplementation have been suggested and are derived almost exclusively from observational studies. Whether other characteristics, including race/ethnicity, BMI, and estimated glomerular filtration rate (eGFR), should also influence the threshold for treatment is unknown. OBJECTIVES: The aim was to identify clinical and biomarker characteristics that modify the response to vitamin D supplementation. METHODS: A total of 666 older adults in the Multi-Ethnic Study of Atherosclerosis (MESA) were randomly assigned to 16 wk of oral vitamin D3 (2000 IU/d; n = 499) or placebo (n = 167). Primary outcomes were changes in serum parathyroid hormone (PTH) and 1,25-dihydroxyvitamin D [1,25(OH)2D] concentrations from baseline to 16 wk. RESULTS: Among 666 participants randomly assigned (mean age: 72 y; 53% female; 66% racial/ethnic minority), 611 (92%) completed the study. The mean (SD) change in PTH was -3 (16) pg/mL with vitamin D3 compared with 2 (18) pg/mL with placebo (estimated mean difference: -5; 95% CI: -8, -2 pg/mL). Within the vitamin D3 group, lower baseline 25-hydroxyvitamin D [25(OH)D] was associated with a larger decline in PTH in a nonlinear fashion. With baseline 25(OH)D ≥30 ng/mL as the reference, 25(OH)D <20 ng/mL was associated with a larger decline in PTH with vitamin D3 supplementation (-10; 95% CI: -15, -6 pg/mL), whereas 25(OH)D of 20-30 ng/mL was not (-2; 95% CI: -6, 1 pg/mL). A segmented threshold model identified a baseline 25(OH)D concentration of 21 (95% CI: 13, 31) ng/mL as an inflection point for difference in change in PTH. Race/ethnicity, BMI, and eGFR did not modify vitamin D treatment response. There was no significant change in 1,25(OH)2D in either treatment group. CONCLUSIONS: Of characteristics most commonly associated with vitamin D metabolism, only baseline 25(OH)D <20 ng/mL modified the PTH response to vitamin D supplementation, providing support from a clinical trial to use this threshold to define insufficiency. This trial was registered at clinicaltrials.gov as NCT02925195.
BACKGROUND: Different 25-hydroxyvitamin D [25(OH)D] thresholds for treatment with vitamin D supplementation have been suggested and are derived almost exclusively from observational studies. Whether other characteristics, including race/ethnicity, BMI, and estimated glomerular filtration rate (eGFR), should also influence the threshold for treatment is unknown. OBJECTIVES: The aim was to identify clinical and biomarker characteristics that modify the response to vitamin D supplementation. METHODS: A total of 666 older adults in the Multi-Ethnic Study of Atherosclerosis (MESA) were randomly assigned to 16 wk of oral vitamin D3 (2000 IU/d; n = 499) or placebo (n = 167). Primary outcomes were changes in serum parathyroid hormone (PTH) and 1,25-dihydroxyvitamin D [1,25(OH)2D] concentrations from baseline to 16 wk. RESULTS: Among 666 participants randomly assigned (mean age: 72 y; 53% female; 66% racial/ethnic minority), 611 (92%) completed the study. The mean (SD) change in PTH was -3 (16) pg/mL with vitamin D3 compared with 2 (18) pg/mL with placebo (estimated mean difference: -5; 95% CI: -8, -2 pg/mL). Within the vitamin D3 group, lower baseline 25-hydroxyvitamin D [25(OH)D] was associated with a larger decline in PTH in a nonlinear fashion. With baseline 25(OH)D ≥30 ng/mL as the reference, 25(OH)D <20 ng/mL was associated with a larger decline in PTH with vitamin D3 supplementation (-10; 95% CI: -15, -6 pg/mL), whereas 25(OH)D of 20-30 ng/mL was not (-2; 95% CI: -6, 1 pg/mL). A segmented threshold model identified a baseline 25(OH)D concentration of 21 (95% CI: 13, 31) ng/mL as an inflection point for difference in change in PTH. Race/ethnicity, BMI, and eGFR did not modify vitamin D treatment response. There was no significant change in 1,25(OH)2D in either treatment group. CONCLUSIONS: Of characteristics most commonly associated with vitamin D metabolism, only baseline 25(OH)D <20 ng/mL modified the PTH response to vitamin D supplementation, providing support from a clinical trial to use this threshold to define insufficiency. This trial was registered at clinicaltrials.gov as NCT02925195.
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Authors: Christopher T Sempos; Ramón A Durazo-Arvizu; Bess Dawson-Hughes; Elizabeth A Yetley; Anne C Looker; Rosemary L Schleicher; Guichan Cao; Vicki Burt; Holly Kramer; Regan L Bailey; Johanna T Dwyer; Xinli Zhang; Jaime Gahche; Paul M Coates; Mary Frances Picciano Journal: J Clin Endocrinol Metab Date: 2013-05-10 Impact factor: 5.958
Authors: Ian H de Boer; David K Prince; Kayleen Williams; Norrina B Allen; Gregory L Burke; Andrew N Hoofnagle; Simon Hsu; Xiaohui Li; Kiang J Liu; Robyn L McClelland; Erin D Michos; Bruce M Psaty; Steven J Shea; Kenneth M Rice; Jerome I Rotter; David S Siscovick; Russell P Tracy; Karol E Watson; Bryan R Kestenbaum Journal: Contemp Clin Trials Date: 2021-02-12 Impact factor: 2.226
Authors: Jimmy T Efird; Ethan J Anderson; Charulata Jindal; Thomas S Redding; Andrew D Thompson; Ashlyn M Press; Julie Upchurch; Christina D Williams; Yuk Ming Choi; Ayako Suzuki Journal: Int J Environ Res Public Health Date: 2021-12-31 Impact factor: 3.390