rhPTH Therapy for Low Turnover Bone Fragility
rhPTH Therapy for Low Turnover Bone Fragility
The purpose of this study is to determine how treatment with a new medication, recombinant
 human parathyroid hormone (rhPTH) affects calcium balance and bone strength.
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