We would like to determine if vitamin D insufficiency exists in different ethnic groups, if it has an effect on bone mass and muscle function, if it has an impact on the function of the cells of the immune system, and if the functioning level of these systems can be improved by stabilizing the vitamin D levels to within normal limits.

Vitamin D is a hormone that can either be made in the skin under the influence of sunlight or absorbed from the diet. Roughly 50% of the U.S. population suffers from an insufficiency of vitamin D and its more active metabolites. This defect can result in disorders in the bones, muscles and immune system. In humans, these disorders usually present themselves as decreased bone mass, decreased muscle strength and increased susceptibility to some infections, respectively.

Therefore, the purpose of this study is to:

1. determine, by use of skeletal and immune biomarkers in the blood and urine, whether vitamin D insufficiency exists in differently pigmented ethnic groups; skin pigmentation blocks vitamin D production in the skin;
2. determine whether the vitamin D status of the host has an impact on bone mass and muscle function;
3. ascertain whether the vitamin D status of the host has an impact on the function of cells of the immune system;
4. determine the effects of correction of vitamin insufficiency on the musculoskeletal and immune systems.

All tests are designed to gauge the state of the circulating and urine factors that contribute to overall calcium balance and/or imbalance. This will include screening for the presence or absence of active and latent infection with the agent that causes TB. If evidence of active TB is identified, one of the physician investigators in this study will inform the subject of the outcome of the screening test and this information will be reported to the California State Health Department.

Additionally, blood and related medical information will ultimately be stored in our UCLA Repository (Human Vitamin D Sample Bank) in the CTRC (Clinical Translational Research Center) in order to allow sharing of the cells with other approved researchers. The cells may be used for other future research related to the purposes described above.

We will enroll vitamin D-deficient subjects (African American, Hispanic and white) and vitamin D-sufficient matching controls against which to compare them. Deficient subjects will be randomized to receive a total of 500,000 IU of vitamin D2 or D3, at the standard replacement dose of vitamin 50,000 IU twice weekly for 5 weeks. Subjects will complete screening medical history, questionnaire, biochemical and DXA (if indicated for low bone mineral density) screening, and exam of muscle strength and/or back curvature (if indicated). Blood and urine will be collected to gauge the state of the circulating and urine factors that contribute to the subjects' overall calcium balance and/or imbalance, and to test for TB. After 5 weeks of vitamin D treatment, subjects will return for repeat testings. Subjects who are still vitamin D-deficient will undergo an additional 5-week regimen. Subjects for whom changes in bone mineral density and/or muscle strength are outcome measures will return one year later for repeat testing.

Inclusion Criteria:

• 25D levels <30 ng/ml (Vitamin D sufficient) OR <20 ng/ml (Vitamin D deficient)
• At least 18 years of age

Exclusion Criteria:

• Hypercalcemia
• Hyperparathyroidism
• Hyperthyroidism
• Hypercalciuria
• Renal disease
• Intestinal malabsorption any disorder that places the subject at risk for developing hypercalcemia or hypercalciuria during standard vitamin D replacement therapy owing to the presence of underlying dysregulated vitamin D metabolism (e.g., sarcoidosis, TB, etc)