Osteoporosis is a major health problem in postmenopausal women. At age 50, half of women will suffer an osteoporotic fracture in their remaining lifetime , causing increased disability and mortality [1, 2]. Vitamin D deficiency, defined as a serum 25(OH)D <15 ng/mL, contributes to osteoporosis via decreased calcium absorption (CaAb), secondary hyperparathyroidism (HPT), increased bone resorption and decreased bone mineral density (BMD) . Thus, experts agree that patients with vitamin D deficiency should receive vitamin D therapy [4-7]. Vitamin D insufficiency (VDI) is a milder form of hypovitaminosis D defined as a 25(OH)D level between 15 and 30 ng/mL regardless of parathyroid hormone (PTH) status . Experts disagree on whether to treat VDI, as the clinical benefits of therapy are uncertain. Some experts [8-11] insist the optimal 25(OH)D level is e30 ng/mL. By contrast, both the Food and Nutrition Board  and NIH Evidence Report No. 158  state that insufficient evidence exists to declare the optimal serum 25(OH)D for bone health, despite review of ~170 studies. Consequently, the Food and Nutrition Board cannot determine a recommended daily allowance for vitamin D. Confusion over the optimal 25(OH)D level results, in part, because previous trials failed to recruit subjects based on initial 25(OH)D levels and/or failed to target or achieve 25(OH)D levels e30 ng/mL. Moreover, secondary HPT, the proposed mechanism by which VDI causes bone loss, occurs in only 10% to 33% of people with VDI [14-17]. As such, people with VDI and normal PTH might not experience clinical benefits from vitamin D therapy. VDI is widespread [15, 18, 19], affecting 26% to 39% of postmenopausal American women with  and without  osteoporosis. Therefore, determining the ideal 25(OH)D level for optimal calcium homeostasis and bone health is of utmost clinical and public health importance. Our overall goal, congruent with Healthy People 2010 objective 2-9, is to evaluate the effect of vitamin D therapy on the risk of osteoporosis in postmenopausal women with VDI, as reflected by changes in CaAb, BMD and muscle fitness. Our second goal is to evaluate whether a high-dose vitamin D regimen, chosen to achieve and maintain a 25(OH)D level e30 ng/mL , is superior in its effects on study outcomes compared to a low-dose vitamin D regimen that can permit continued VDI [22-25].
One in two women past menopause has mildly low vitamin D levels. We don't know if vitamin D therapy helps these women to have stronger bones that break less easily. We also don't know whether high-dose vitamin D therapy is better than low-dose vitamin D, in its effects on calcium absorption, bone calcium levels and muscle function. We will ask 250 women past menopause with mildly low vitamin D levels to take part in a one year study. One third of women will receive placebo, one-third will receive low-dose vitamin D and one-third will receive a high-dose vitamin D tablet that keeps their blood levels above 30 ng/mL. We will compare the changes in calcium CaAb, bone calcium levels and muscle fitness among women receiving placebo, low-dose vitamin D and high- dose vitamin D. This study will help decide whether vitamin D therapy lessens the risk of osteoporosis in postmenopausal women, and at what vitamin D dose those benefits occur.
|Ramsubeik, Karishma; Keuler, Nicholas S; Davis, Lisa A et al. (2014) Factors associated with calcium absorption in postmenopausal women: a post hoc analysis of dual-isotope studies. J Acad Nutr Diet 114:761-7|
|Hansen, K E; Blank, R D; Palermo, L et al. (2014) What analytic method should clinicians use to derive spine T-scores and predict incident fractures in men? Results from the MrOS study. Osteoporos Int 25:2181-8|
|Hansen, Karen E; Nabak, Andrea C; Johnson, Rachael Erin et al. (2014) Isotope concentrations from 24-h urine and 3-h serum samples can be used to measure intestinal magnesium absorption in postmenopausal women. J Nutr 144:533-7|
|Hansen, Karen E; Bartels, Christie M; Gangnon, Ronald E et al. (2014) An evaluation of high-dose vitamin D for rheumatoid arthritis. J Clin Rheumatol 20:112-4|
|Hansen, Karen E; Ney, Denise (2014) A systematic review of bone mineral density and fractures in phenylketonuria. J Inherit Metab Dis 37:875-80|
|Hansen, Karen E; Kleker, Brian; Safdar, Nasia et al. (2014) A systematic review and meta-analysis of glucocorticoid-induced osteoporosis in children. Semin Arthritis Rheum 44:47-54|
|Nabak, Andrea C; Johnson, Rachael Erin; Keuler, Nicholas S et al. (2014) Can a questionnaire predict vitamin D status in postmenopausal women? Public Health Nutr 17:739-46|
|Swenson, Erik D; Hansen, Karen E; Jones, Andrea N et al. (2013) Characteristics associated with bone mineral density responses to alendronate in men. Calcif Tissue Int 92:548-56|
|Jones, A N; Shafer, M M; Keuler, N S et al. (2012) Fasting and postprandial spot urine calcium-to-creatinine ratios do not detect hypercalciuria. Osteoporos Int 23:553-62|
|Hansen, Karen E (2011) High-dose vitamin D: helpful or harmful? Curr Rheumatol Rep 13:257-64|
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