How Does Magnesium Status Influence Calcium Homeostasis?

The investigators aim to recruit 60 women who have agreed to participate in an existing randomized, double-blind, placebo-controlled trial (Treatment of Vitamin D Insufficiency, HSC 2009-0055). In this trial, the investigators propose to evaluate the associations between magnesium intake, magnesium stores, fractional magnesium absorption and calcium homeostasis. The investigators will stratify 60 subjects in the sub-study, ensuring that approximately 20 subjects are randomized into each treatment arm (placebo, low-dose and high-dose vitamin D). The investigators already assess calcium homeostasis throughout the study by measuring bone mineral density, fractional calcium absorption, serum and urine calcium levels, among other tests. In the sub-study of 60 women, the investigators will evaluate whether habitually higher magnesium intake increases or decreases fractional calcium absorption. The investigators will evaluate the interplay between magnesium stores, vitamin D levels and serum parathyroid hormone levels. The investigators will directly assess magnesium stores using serum magnesium and 24-hour urine magnesium levels, and will measure magnesium absorption using the dual stable isotope approach.

Use of serum magnesium isotopes to measure fractional magnesium absorption Four day food diaries to assess magnesium intake Standard urine and serum chemistries for remaining labs as noted above

50,000 IU vitamin D3 every 15 days, with a loading dose of 50,000 IU per day for the first 15 days of an approximate 365-day treatment.

A pill that looks like the low/high dose vitamin D pills, but contains no vitamin D. Given to preserve the double-blind nature of the study.

Evaluate the associations between magnesium intake, magnesium stores, fractional magnesium absorption and calcium homeostasis.

To evaluate relationships between magnesium intake and fractional magnesium absorption at baseline and 12 months, among 60 women participating in HSC Protocol 2009-0055, and to assess whether vitamin D therapy influences magnesium absorption among these women. We will also evaluate whether data collected from less than 72 hours of urine following tracer administration permits accurate assessment of fractional magnesium absorption.

Does vitamin D therapy have a differential impact on calcium absorption that is dependent on magnesium stores?

To assess whether vitamin D therapy has a differential impact on calcium absorption, depending on magnesium stores. We will use data from all subjects participating in HSC Protocol 2009-0055 to evaluate whether magnesium status is a co-factor in the change in calcium absorption that occurs with vitamin D therapy.

Evaluate how magnesium status impacts the relationship between vitamin D levels and parathyroid hormone levels.

Inclusion Criteria: participants eligible for the study "Treatment of vitamin D insufficiency" are eligible for participation in the current sub-study Exclusion Criteria: identical to those covered in HSC #2009-0055

Hansen KE, Nabak AC, Johnson RE, Marvdashti S, Keuler NS, Shafer MM, Abrams SA. Isotope concentrations from 24-h urine and 3-h serum samples can be used to measure intestinal magnesium absorption in postmenopausal women. J Nutr. 2014 Apr;144(4):533-7. doi: 10.3945/jn.113.186767. Epub 2014 Feb 5.