Vitamin D and Osteoporosis Prevention in Elderly African American Women

The long-term goal of this project is to develop strategies for the prevention of
osteoporotic fractures in African Americans. Most intervention studies have excluded African
Americans because of the erroneous belief that osteoporosis is not a major health problem in
this population. In fact, the incidence rate of hip fracture in blacks is 50% of the rate in
whites. Since longevity is increasing in the black population, osteoporotic fractures will
become an even greater problem for this ethnic minority in the future. Furthermore, morbidity
and mortality from osteoporotic fractures is greater in blacks. The elderly require higher
intake of vitamin D to prevent bone loss resulting from secondary hyperparathyroidism.
Calcium with sufficient vitamin D supplementation may decrease fractures in elderly white
populations as a result of reduction in bone loss and falls (improved physical performance).
The only fracture intervention study to include African Americans—the Women's Health
Initiative—used an inadequate dose of vitamin D (400 IU), a dose unlikely to achieve the
vitamin D status proposed by U.S. experts: serum 25 hydroxyvitamin D [25(OH)D] concentration
above 75 nmol/L. No calcium/vitamin D intervention studies on fall prevention or physical
performance have included African Americans.

As a result of increased skin pigmentation, blacks synthesize less vitamin D from sun
exposure. As a result, serum 25(OH)D levels are often in the "insufficient" range. This is
accompanied by secondary hyperparathyroidism, but adult blacks have a relative skeletal
resistance to PTH, so that they have lower bone turnover. They also have more efficient renal
conservation of calcium starting in childhood. Addition of vitamin D3 to a calcium-sufficient
African American postmenopausal population does not prevent bone loss. The calcium/vitamin D
requirements of black adults may be lower than white adults through midlife. However, the
elderly require more vitamin D to produce the higher 25(OH)D levels required to overcome the
hyperparathyroidism associated with aging. The skeleton of elderly African Americans appears
to be susceptible to the increasing parathyroid hormone levels of old age. Bone loss
accelerates and bone turnover markers increase in elderly African Americans just as in
whites. The specific aims of this project are to determine if dietary supplementation with
calcium/vitamin D will safely reduce bone loss and bone turnover and improve physical
performance in elderly African Americans. We will enroll 250 African American women in a
four-year vitamin D3 intervention trial where serum 25(OH)D will be maintained at an optimum
level above 75 nmol/L. Adequate calcium intake will be ensured. Functional markers of vitamin
D including bone density, serum PTH, and bone turnover will be measured. The NIH Conference
on Vitamin D and Health in the 21st Century, September 5-6, 2007 concluded that research in
this population is a high priority.

Inclusion Criteria:

1. Ambulatory women older than 60 years of age. Self declared as African Americans.

2. 20 nmol/L < serum 25(OH)D level < 65 nmol/L.

3. Willingness to take study drug and participate for four years in the trial.

4. Willingness to refrain from the use of self-administered supplements during the trial.

Exclusion Criteria:

1. Serum 25(OH)D levels ≤ 20 nmol/L or ≥ 65 nmol/L.

2. BMD total hip below - 2.5 standard deviation (using NHANES III adult young white men
and women as the point of reference) or history of osteoporotic fracture.

3. Moderate to severe fracture in one or more vertebrae by Instant Vertebral Assessment
on DXA.

4. Treatment with HRT, SERMS, calcitonin, PTH, androgens, bisphosphonates, phosphate or
anabolic steroids during 6 months prior to entry.

5. Use of systemic corticosteroids (oral or IV) within the last year at an average dose
of greater than 5 mg per day of oral prednisone or equivalent for a period of three
months or more prior to screening.

6. Hypercalcemia (serum calcium > 10.6 mg (dl) or history of primary hyperparathyroidism.

7. History of chronic liver disease, chronic renal insufficiency, Parkinson's, metabolic
bone disease, hematologic tumors, rheumatologic disease requiring steroids,
malabsorption or new diagnosis or active treat-ment of cancer 12 months prior to
inclusion.

8. Use of medications that influence bone metabolism (e.g. anticonvulsants).

9. Significant deviation from normal in either: history, physical examination or
laboratory tests as evaluated by the Principle Investigator. Participants with a
history of hypercalciuria, nephrolithiasis and active sarcoidosis will also be
excluded.

10. Participation in another investigational trial 30 days prior to screening.

11. Spinal disease that affects interpretation of bone densitometry like scoliosis with a
Cobb angle greater than 15o, history of surgery at lumbosacral spine.

12. Bilateral hip replacement.

13. Currently smoking more than 10 cigarettes daily.

14. Body width on DXA > 25 cm.

15. Patients who are deemed unsafe to perform muscular function testing as evaluated by
the investigator.

---------- Study participants should live close to the study site, as this study
requires multiple visits over a four year period.