Dose-dependent Effects of Vitamin D on Bone Health

Hypotheses being tested: 1. It is hypothesized that vitamin D, in a dose-dependent manner, will suppress parathyroid hormone action, resulting in less bone turnover, and decreased cortical porosity, leading to improved bone strength as assessed by finite element analysis. 2. It is hypothesized that vitamin D, in a dose-dependent manner, will increase bone density in the central skeleton (spine, hip), as measured by the current standard method of dual X-ray absorptiometry (DXA). 3. It is hypothesized that vitamin D, in a dose-dependent manner, will have an impact on quality of life, including indices of depression, as measured by the SF-36 questionnaire and an appropriate index of depression. Outcomes: Primary outcomes: * (1) bone density and (2) strength as measured by HR-pQCT Secondary outcomes: * HR-pQCT assessment of bone microarchitecture, examining the relative contribution of trabecular and cortical bone. We have chosen four parameters for statistical analysis, and have listed them as secondary outcome variables in the section below: cortical density, cortical porosity, trabecular density and trabecular number. * bone mineral density as measured by DXA * parameters of calcium metabolism, including biochemical markers of bone turnover and DNA to examine possible variations in the genes that control vitamin D metabolism. * quality of life score * depression scale score * balance, grip strength. * fasting glucose and Hemoglobin A1C will also be measured. * Safety will be assessed during the scheduled follow-up visits by obtaining history of adverse events, as well as measurements of serum and urine parameters of mineral metabolism as described below. INTERVENTION DRUG: Vitamin D3 in one of three doses Rationale: For adults under age 70 years, the recent Institute of Medicine (IOM) report recommends a total intake of 600 IU vitamin D/day will provide all the vitamin D needed for bone health, and since the typical Canadian diet contains between 200 and 300 units of vitamin D, the subjects in the lowest dose arm of our study will receive 400 IU/day. The other two groups will receive 10,000 IU and 4,000 IU, respectively. The 10,000 IU dose is the tolerable upper intake level (TUL) recommended by Hathcock et al (Am J Clin Nutr 2007) and 4,000 IU is the IOM's recommended TUL. Calcium intake: All subjects will have adequate calcium intake as defined by the Institute of Medicine (total of 1200 mg/day). A brief dietary history will be taken and subjects will be instructed to take an appropriate dose of supplemental calcium if their daily intake is less than 1200 mg/day (the IOM's Recommended Daily Allowance for this study population). Interim analysis (with maintenance of blinding of subjects and investigators as to treatment arm): * planned at and of years 1 and 2, as well as the final analysis at year 3.