Does Treatment of Hypovitaminosis D Increase Calcium Absorption?

The purpose is to perform a one-year study designed to assess whether treatment of hypovitaminosis D increases intestinal absorption of calcium, subsequent retention of calcium within bone, decreases bone turnover, and favorably impacts upon skeletal muscle mass, functional status, measures of physical function and quality of life. I hypothesize that treatment of hypovitaminosis D results in improved intestinal calcium absorption, greater retention of calcium within the bone reservoir and improved physical function, quality of life and muscle mass.

Postmenopausal women with vitamin D insufficiency will participate in this one-year study. We will study the change in intestinal calcium absorption from baseline (vitamin D insufficiency) to follow up (vitamin D repletion and whether increased absorption results in subsequent increased retention of calcium within bone over the one-year interval as measured by bone densitometry. We will also study the effect of vitamin D repletion upon whole body muscle mass, quality of life and physical function.

A review of medical records and a screening visit will determine eligibility. Eligible and consenting subjects will present to the GCRC in the early morning and following baseline labs, will consume breakfast with a glass of orange juice enriched with a stable calcium isotope, and will receive 3 mg of another stable calcium isotope by intravenous injection. Over the next eight hours, blood will be taken a total of 9 more times and over the first 24 hours, all urine and stool will be collected for measurement of its calcium content.

Subsequently for the next five days, women will collect three urine specimens daily. Women will then receive vitamin D to treat vitamin D deficiency. Once vitamin D repletion is accomplished, all women will repeat their 24-hour visit and subsequent five-day urine collections. Women will maintain vitamin D repletion by taking a twice monthly tablet (50,000 IU) of vitamin D2. To confirm vitamin D repletion and safety over the full one year study, additional study visits will occur at 3, 6 and 12 months.

A bone density test at screening and twelve months will allow us to assess the effect of vitamin D repletion on whole body bone mass and skeletal mass. At each GCRC stay, 3, 6 and 12 months, women will complete questionnaires regarding quality of life and functional status and will perform the Timed Up and Go Test. Because we wish to maintain and confirm constant calcium intake throughout the one- year study, women will complete a calcium questionnaire at baseline, 3, 6 and 12 months.

With each subject's consent, we will collect one tube of blood and isolate its DNA. When sufficient knowledge is available regarding the pathophysiologic mechanisms whereby genetic polymorphisms impact calcium homeostasis, we will test for such DNA polymorphisms and relate genetic information with other data collected on calcium homeostasis.

Eligibility Criteria:
Inclusion Criteria:

* women at least five years past onset of menopause, defined as date of last menses (ages reported above are the range in ages of the participants recruited to the study)
* serum 25(OH)D 16-24 ng/ml by reverse phase HPLC
* calcium intake \< or = 1,100 mg daily

Exclusion Criteria:

* Intake of \>1,100 mg of calcium per day through the combination of diet and supplements
* Hypercalcemia (baseline serum calcium above the normal reference range)
* Nephrolithiasis, documented in the medical record or by patient report
* Inflammatory bowel disease, malabsorption, chronic diarrhea, or use of antibiotics within the past month
* Creatinine \>2.0 mg/dL
* Hypercalciuria (baseline urine calcium: creatinine ratio \>0.25)
* Current use of medications known to interfere with vitamin D and/or calcium metabolism, including oral steroids or anticonvulsants
* Ongoing or recent (past six months) use of bisphosphonates, estrogen compounds, calcitonin or teriparatide, as these compounds may independently affect retention of calcium within bone
* Diagnosis of, or evidence for, osteomalacia, manifest by serum 25(OH)D \< 16 ng/ml or the presence of at least two of the following blood tests: low calcium, low phosphorus, or elevated alkaline phosphatase (23).
* Prior adult clinical fragility fracture or baseline T-score below -3.0 at the lumbar spine or femur