rhPTH Therapy for Low Turnover Bone Fragility

Subjects will have had a bone biopsy to definitively determine low bone turnover. Subjects
and the treating doctor decide that treatment with rhPTH (recombinant human parathyroid
hormone) is optimal before admission into the study. During the study, subjects will have
several tests that will clarify how rhPTH is affecting calcium metabolism and bone
properties. All of the studies will be performed in the University of Chicago General
Clinical Research Center (GCRC).

To examine the effects of PTH (parathyroid hormone) on calcium metabolism, subjects will be
admitted to the GCRC for 3 days in the beginning of the study. Subjects will have a plastic
needle inserted into a vein to enable the nurses to draw your blood repeatedly without
having to stick you every time. Subjects will have 120 mL (about 8 tablespoons) of blood
drawn during the 3 day period. Subjects will be allowed to choose the food from the regular
hospital menu but the amount of calcium from the diet will be the same during each day that
you spend in the GCRC. The first day will be used to observe calcium balance without
medication while the subsequent 2 days will be used to determine how calcium balance changes
in response to the medication rhPTH. Subjects will take the medication in the morning,
before breakfast - this will be considered time 0. During all 3 days, blood will be taken at
0, 2, 4, 6, 8, 12, 16, and 20 hours for examination of serum calcium and at 0, 4 and 12
hours for measurement of PTH (that is produced by your body).

On the first and 3rd day all the urine will be collected to measure how much calcium is lost
in the urine.

After Subjects have received the medication for 3 months they will again be admitted to the
GCRC, this time for 2 days during which they will continue to take the medication with the
same measurements as on the last 2 days of the first admission. The same admission will be
repeated after 12 months of treatment. During each of these admissions, you will have 80 mL
(about 5 ½ tablespoons) of blood drawn.

In addition to these 3 inpatient stays in the CRC, subjects will also have several tests as
an outpatient. The tests will be used to evaluate the effect of rhPTH on the bone. To this
end, you will have 3 types of tests.

1. To evaluate the bone turnover (activity of bone cells) subjects will have blood and
urine collected for measurement of biochemical markers of bone turnover (chemicals in
the blood and urine that reflect the activity of bone cells) measured before and at 1,
2, 3, 6, 9, and 12 months. Subjects will have 10 mL (about 2 teaspoons) of blood drawn
at each of these visits.

2. To evaluate changes in the bone density subjects will have bone density test of the
lumbar spine, hip, heel and wrist measured every 3 months for 12 months.

3. To evaluate changes in the architecture or structure of the bone subjects will have 2
tests. First, the heel images that are obtained during the bone density test (under #2)
will be subjected to radiographic texture analysis. This is a method of computerized
analysis of the pattern of bone radiographic images which is supposed to differentiate
between strong and weak bone based on the difference in the radiographic texture. The
second test will be a bone biopsy. A bone biopsy involves inserting a needle through
the skin and directly into the bone to obtain a piece of the bone of 1 cm (less than ½
inch) in length and 0.3 cm (1/10 inch) in diameter. Before this biopsy needle is
inserted a numbing medication is injected to prevent pain during the procedure. You
will also receive a medication through the vein so that you will be almost asleep
during the procedure (intravenous sedation). Most people only experience minor pain for
a few days after the biopsy. Subjects will have had the first bone biopsy before
enrolling into this study. A second bone biopsy will be performed after 12 months of
treatment with rhPTH.

Inclusion Criteria:

- :patients with history of increased bone fragility by BMD criteria (T score > -1). In
addition, the subjects will be enrolled only if they have clear evidence of low bone
turnover as indicated by low normal levels of biochemical markers of bone turnover
and finding of low bone turnover on bone biopsy. Each subject and his/her treating
physician will have agreed that the rhPTH is the best treatment for the patient.
Treatment with rhPTH will be considered only if the bone histomorphometry reveals a
low turnover state and excludes other known forms of bone disease such as
osteomalacia.

Exclusion Criteria:

- Subjects who are pregnant or younger than 20 will be excluded. Subjects cannot have
osteoporosis