Primary Hyperparathyroidism (PHPT): Early Effect of Vitamin D

Primary hyperparathyroidism (PHPT) is a common disease that occurs in 1 in 10,000 people
every year. In the presence of this condition, the parathyroid glands produce excessive
amounts of parathyroid hormone (PTH), which regulates calcium levels. The high levels of
parathyroid hormone remove too much calcium from bones, and then deposit the excess calcium
in the blood, which is then filtered into the urine by the kidneys. Bone health is
threatened by excess calcium loss which weakens bone structure. Other affected organs
include the skeleton (calcium loss leads to a "weakening" of the skeleton), and the kidneys
(high blood calcium can lead to kidney stones).

It is now evident that the majority of patients with even mild Primary Hyperparathyroidism
are vitamin D deficient. In 2009, new international guidelines for the management of
asymptomatic PHPT direct physicians to measure 25-hydroxyvitamin D (D3 or 25-OHD) in all
patients, and to replete the reserve of vitamin D when the level is low (< 20 ng/ml).
However, no recommendations for vitamin D repletion are given, because of limited data
regarding the effects of vitamin D repletion, appropriate dosing and safety. Therefore,
there is an urgent need for data upon which to base such recommendations, as well as are
data on the effects of such treatment upon bones.

Subjects with low vitamin D3 levels will be selected for this trial. They will be given
enough vitamin D3 to raise their low blood levels from a low to a normal range. The
assessments in this study, including the quadruple label bone biopsy, will allow us to
document the short term effects of administering vitamin D3 on changes in bone.

All participants enrolled in this trial will be vitamin D3 deficient. Participants will
take an antibiotic (tetracycline) 4 times a day to mark the starting point from which bone
changes will be assessed. After 3 days of tetracycline, a 12 week course of vitamin D3 or
placebo will be initiated. Six of 7 participants will receive the study drug (active
vitamin D3), while 1 in 7 will receive a placebo (sugar pill). Ten weeks later, another
3-day course of tetracycline will be given. At the end of 12 weeks, a bone biopsy will be
done. A small piece of bone (about the size of a pencil eraser) will be removed from the
hip (iliac crest). The bone will be analyzed to determine the effect of vitamin D3 on
primary hyperparathyroidism.

There will be 4 study visits: Screening, Baseline, Week 8, and Week 12 when the bone biopsy
will be performed.

Study Procedures:

Medical and Social History

Blood tests (drawn at the study center and local Quest Lab)

24-Hour urine collection for calcium and creatinine excretion

Abdominal X-ray (to assess for kidney stones)

Transiliac crest Bone Biopsy