• Calcium absorption [ Time Frame: Baseline and every 3 months ] [ Designated as safety issue: No ]
• Serum/urine calcium [ Time Frame: Baseline and every 3 months ] [ Designated as safety issue: Yes ]
• Bone markers [ Time Frame: Baseline and every 3 months ] [ Designated as safety issue: No ]
• Bone density [ Time Frame: Baseline and every 3 months ] [ Designated as safety issue: No ]
• Muscle strength [ Time Frame: Baseline and every 3 months ] [ Designated as safety issue: No ]
• Falls [ Time Frame: Baseline and every 3 months ] [ Designated as safety issue: No ]

• Calcium absorption
• serum/urine calcium
• bone markers
• bone density
• muscle strength
• falls

The purpose of this study is to examine the effects of several doses of vitamin D on hormones related to bone, calcium absorption, bone density and muscle strength.

The prevalence of osteoporosis is high in the United States, with about 10 million people over the age of 50 already having the disease and another 34 million at risk for developing it. Development of low-cost and effective strategies is important for preventing osteoporosis and reducing osteoporotic fractures. A simple inexpensive strategy to prevent osteoporosis is adequate nutrition with calcium and vitamin D. Serum 25OHD (25-hydroxyvitamin D) is now accepted as the objective measure of vitamin D nutrition. There is a growing understanding that serum 25OHD concentrations of at least 30-32 ng/ml are needed for optimal bone health at which serum parathyroid hormone (PTH) concentrations reach a minimum.

There are no systematic prospective dose response studies aimed at determining the optimum amount of vitamin D intake required to maintain optimum serum 25OHD levels in the population which will help in determining the estimated average requirement (EAR) and recommended dietary requirement (RDA) for vitamin D. More work to determine the RDA for vitamin D has been recommended by the Panel on Calcium and Related Nutrients of the Food and Nutrition Board. This study is aimed at filling the information gap by concentrating on the high risk group of postmenopausal women. We are testing the theory that increasing serum 25OHD to a level greater than 30 ng/ml will reduce serum PTH in the high risk group of vitamin D insufficient postmenopausal women with an adequate intake of calcium. We also believe that the dose of vitamin D that will achieve this level is approximately 4400IU per day, which is well above the suggested adequate intake of 400-600 ID recommended for the elderly.

In a one year double blind, randomized prospective clinical trial, we will examine the dose response effect of supplementation with different doses of vitamin D3 (400, 800, 1600, 2400, 3200, 4000, 4800IU/day) on the primary outcomes of serum 25OHD and PTH in 160 postmenopausal Caucasian and 160 African American women who have inadequate vitamin D levels in winter. We expect that the results from this study will add useful and important information about the RDA for vitamin D for postmenopausal women who are more susceptible to osteoporosis. The results from this study will also help in designing future clinical trials to study the effect of vitamin D, for example in preventing fractures, falls, cancer.

Progress: Caucasian enrollment completed July 2008; African American enrollment continuing.

• Osteoporosis
• Aging

• Drug: Vitamin D3
• Drug: Calcium Citrate (Citracal)

• Experimental: 400 IU per day
• Experimental: 800 IU per day
• Experimental: 1600 IU per day
• Experimental: 2400 IU per day
• Experimental: 3200 IU per day
• Experimental: 4000 IU per day
• Experimental: 4800 IU per day

• Gallagher JC, Kinyamu HK, Fowler SE, Dawson-Hughes B, Dalsky GP, Sherman SS. Calciotropic hormones and bone markers in the elderly. J Bone Miner Res. 1998 Mar;13(3):475-82.
• Holick MF, Siris ES, Binkley N, Beard MK, Khan A, Katzer JT, Petruschke RA, Chen E, de Papp AE. Prevalence of Vitamin D inadequacy among postmenopausal North American women receiving osteoporosis therapy. J Clin Endocrinol Metab. 2005 Jun;90(6):3215-24. Epub 2005 Mar 29.
• Aloia JF, Talwar SA, Pollack S, Feuerman M, Yeh JK. Optimal vitamin D status and serum parathyroid hormone concentrations in African American women. Am J Clin Nutr. 2006 Sep;84(3):602-9.

Inclusion Criteria:

• At least 7 years post-menopause
• Serum 25OHD level 5 ng/ml to 20 ng/ml
• BMI less than or equal to 40 kg/m2
• Willing to discontinue multivitamins that contain vitamin D during the study

Exclusion Criteria:

• Cancer (except basal cell carcinoma) or terminal illness
• Previous hip fracture
• Hemiplegia (paralysis of one side of the body)
• Uncontrolled type I diabetes or fasting blood sugar greater than 140 mg in type II
• Kidney stones more than twice in a lifetime
• Chronic renal failure
• Evidence of chronic liver disease, including alcoholism
• Physical conditions such as severe osteoarthritis, rheumatoid arthritis, heart failure severe enough to prevent reasonable physical activity
• Previous treatment with bisphosphonates (more that 3 months), PTH or PTH derivatives, (e.g. Teriparatide or Fluoride) in the last 6 months
• Previous treatment within the last 6 months with calcitonin or estrogen
• Chronic high dose corticosteroid therapy (more than 10 mg per day) for over 6 months and not within the last 6 months
• Anticonvulsant therapy
• High dose thiazide therapy (more than 37.5 mg)
• 24 hour urine calcium greater than 290 mg on 2 baseline tests
• Serum calcium exceeding upper normal limit on 2 baseline tests
• Bone Mineral Density T-score less than -3.0 for spine or hip