Effects of PTH Replacement on Bone in Hypoparathyroidism

Participants (in Cohorts 2 and 3) were randomized to receive their second bone biopsy at year 1, 2, or 4 after the start of HPTH therapy. For Cohort 2, the baseline bone biopsy was completed at the start of CC on the original protocol. For Cohort 3, the baseline biopsy was completed immediately prior to the first HPTH dose. Because the sample sizes for the 1-, 2- and 4-year biopsies are reduced due to the early termination of the study, so the 2-, and 4-year biopsies were collapsed into one biopsy year group. Cn.BV/TV is one of 8 primary endpoints measured from the bone biopsy. The changes in Cn.BV/TV outcome between two time-points are being reported. The unit of measure is a z-score. Z-scores are normed to standard populations to a mean of zero and a standard deviation of 1. The normal range for a z-score is from -2 to 2. Values above or below this normal range are considered worse outcomes.

Time frame: Baseline, 1 year bone biopsy, and combined 2 and 4 year bone biopsies

Population: The Bone Biopsy Analysis Population was used for the primary bone biopsy biomarkers. The Bone Biopsy Population consisted of all participants in Cohorts 2 and 3 who completed both their baseline and randomized 1, 2, or 4 year bone biopsies.

Participants (in Cohorts 2 and 3) were randomized to receive their second bone biopsy at year 1, 2, or 4 after the start of HPTH therapy. For Cohort 2, the baseline bone biopsy was completed at the start of CC on the original protocol. For Cohort 3, the baseline biopsy was completed immediately prior to the first HPTH dose. Because the sample sizes for the 1-, 2- and 4-year biopsies are reduced due to the early termination of the study, the 2-, and 4-year biopsies were collapsed into one biopsy year group. Cn.BFR/BS, measured from the bone biopsy, is the cancellous bone formation rate per unit of bone surface where cancellous refers to the spongy structure of the bone. The changes in Cn.BFR/BS between two time-points are being reported. The unit of measure is a z-score. Z-scores are normed to standard populations to a mean of zero and a standard deviation of 1. The normal range for a z-score is from -2 to 2. Values above or below this normal range are considered worse outcomes.

Time frame: Baseline, 1 year bone biopsy, and combined 2 and 4 year bone biopsies

Population: The Bone Biopsy Analysis Population was used for the primary bone biopsy biomarkers. The Bone Biopsy Population consisted of all participants in Cohorts 2 and 3 who completed both their baseline and randomized 1, 2, or 4 year bone biopsies.

Following their baseline bone biopsy, 5, 5, and 2 participants were randomized to receive their second bone biopsy at years 1, 2, and 4 after the start of HPTH therapy, respectively. Because the sample sizes for the 1-, 2- and 4-year biopsies are reduced in size due to withdrawal and the early termination of the study, the 2-, and 4-year biopsies were collapsed into one biopsy year group. Cn.MS/BS is measured from the bone biopsy. This measure demonstrates the percentage of the cancellous bone surface that is actively forming bone. The region of interest is the predefined area of total bone that is being measured. The changes in Cn.MS/BS between two time-points are being reported.

Time frame: Baseline, 1 year bone biopsy, and combined 2 and 4 year bone biopsies

Population: The Bone Biopsy Analysis Population was used for the primary bone biopsy biomarkers. The Bone Biopsy Population consisted of all participants in Cohorts 2 and 3 who completed both their baseline and randomized 1, 2, or 4 year bone biopsies.

Participants (in Cohorts 2 and 3) were randomized to receive their second bone biopsy at year 1, 2, or 4 after the start of HPTH therapy. For Cohort 2, the baseline bone biopsy was completed at the start of CC on the original protocol. For Cohort 3, the baseline biopsy was completed immediately prior to the first HPTH dose. However, because the sample sizes for the 1-, 2- and 4-year biopsies are reduced due to the early termination of the study, the 2-, and 4-year biopsies were collapsed into one biopsy year group. Ec.BFR/BS is measured from the bone biopsy. This measures the rate of new bone formation per day on the inner cortical (endocortical) surface in a predefined region of cortical bone. The changes in Ec.BFR/BS between two time-points are being reported. The n's in the outcome measure table refer to the number of complete records (non-missing baseline and post-baseline measures).

Time frame: Baseline, 1 year bone biopsy, and combined 2 and 4 year bone biopsies

Population: The Bone Biopsy Analysis Population was used for the primary bone biopsy biomarkers. The Bone Biopsy Population consisted of all participants in Cohorts 2 and 3 who completed both their baseline and randomized 1, 2, or 4 year bone biopsies.

Participants (in Cohorts 2 and 3) were randomized to receive their second bone biopsy at year 1, 2, or 4 after the start of HPTH therapy. For Cohort 2, the baseline bone biopsy was completed at the start of CC on the original protocol. For Cohort 3, the baseline biopsy was completed immediately prior to the first HPTH dose. Because the sample sizes for the 1-, 2- and 4-year biopsies are reduced due to the early termination of the study, the 2-, and 4-year biopsies were collapsed into one biopsy year group. Ec.MS/BS is measured from the bone biopsy. This measure demonstrates the percentage of the endocortical bone surface that is actively forming bone. The region of interest is the predefined area of total bone that is being measured. The changes in Ec.MS/BS between two time-points are being reported. The n's in the outcome measure table refer to the number of complete records (non-missing baseline and post-baseline measures).

Time frame: Baseline, 1 year bone biopsy, and combined 2 and 4 year bone biopsies

Population: The Bone Biopsy Analysis Population was used for the primary bone biopsy biomarkers. The Bone Biopsy Population consisted of all participants who completed both their baseline and randomized 1, 2, or 4 year bone biopsies. This will only include participants from cohorts 2 and 3.

Participants (in Cohorts 2 and 3) were randomized to receive their second bone biopsy at year 1, 2, or 4 after the start of HPTH therapy. For Cohort 2, the baseline bone biopsy was completed at the start of CC on the original protocol. For Cohort 3, the baseline biopsy was completed immediately prior to the first HPTH dose. However, because the sample sizes for the 1-, 2- and 4-year biopsies are reduced due to the early termination of the study, the 2-, and 4-year biopsies were collapsed into one biopsy year group. Ic.BFR/BS is measured from the bone biopsy. This measures the rate of new bone formation between the two cortical surfaces (intracortical) in a predefined region of cortical bone. The changes in Ic.BFR/BS between two time-points are being reported. The n's in the outcome measure table refer to the number of complete records (non-missing baseline and post-baseline measures).

Time frame: Baseline, 1 year bone biopsy, and combined 2 and 4 year bone biopsies

Population: The Bone Biopsy Analysis Population was used for the primary bone biopsy biomarkers. The Bone Biopsy Population consisted of all participants in Cohorts 2 and 3 who completed both their baseline and randomized 1, 2, or 4 year bone biopsies.

Participants (in Cohorts 2 and 3) were randomized to receive their second bone biopsy at year 1, 2, or 4 after the start of HPTH therapy. For Cohort 2, the baseline bone biopsy was completed at the start of CC on the original protocol. For Cohort 3, the baseline biopsy was completed immediately prior to the first HPTH dose. Because the sample sizes for the 1-, 2- and 4-year biopsies are reduced due to the early termination of the study, the 2-, and 4-year biopsies were collapsed into one biopsy year group. Ic.MS/BS is measured from the bone biopsy. This measure demonstrates the percentage of the intracortical bone surface that is actively forming bone. The region of interest is the predefined area of total bone that is being measured. The changes in Ic.MS/BS between two time-points are being reported. The n's in the outcome measure table refer to the number of complete records (non-missing baseline and post-baseline measures).

Time frame: Baseline, 1 year bone biopsy, and combined 2 and 4 year bone biopsies

Population: The Bone Biopsy Analysis Population was used for the primary bone biopsy biomarkers. The Bone Biopsy Population consisted of all participants in Cohorts 2 and 3 who completed both their baseline and randomized 1, 2, or 4 year bone biopsies.

Participants (in Cohorts 2 and 3) were randomized to receive their second bone biopsy at year 1, 2, or 4 after the start of HPTH therapy. For Cohort 2, the baseline bone biopsy was completed at the start of CC on the original protocol. For Cohort 3, the baseline biopsy was completed immediately prior to the first HPTH dose. Because the sample sizes for the 1-, 2- and 4-year biopsies are reduced due to the early termination of the study, so the 2-, and 4-year biopsies were collapsed into one biopsy year group. Ct.Po.N is a bone biopsy measure that assess the amount of holes in the cortical bone within a predetermined area of cortical bone. The changes in Cn.BV/TV outcome between two time-points are being reported. Cortical bone with a higher number of holes may be at greater risk of fracture. The n's in the outcome measure table refer to the number of complete records (non-missing baseline and post-baseline measures).

Time frame: Baseline, 1 year bone biopsy, and combined 2 and 4 year bone biopsies

Population: The Bone Biopsy Analysis Population was used for the primary bone biopsy biomarkers. The Bone Biopsy Population consisted of all participants in Cohorts 2 and 3 who completed both their baseline and randomized 1, 2, or 4 year bone biopsies.

Urine was collected over 24 hours and the total NTX Telopeptide measured

Time frame: Baseline, last visit on HPTH (up to 5 years), and post-HPTH follow-up visit (6 months post last visit on HPTH)

Population: Secondary Efficacy Population: This population consists of all participants who received at least one dose of HPTH and had at least one post-baseline non-biopsy efficacy assessment. This population will only include participants in Cohorts 2 and 3.

Severity is measured using four separate items of the FSI questionnaire that assesses how the participant felt on their most, least, and average fatigue days in the past week as well as current fatigue. Participants score their level of fatigue for each item on an 11-point scale (0=not at all fatigued, 10=as fatigued as I could be). An average is taken of sum of these 4 scores. The average severity score can range from 0 to 10. A higher average severity score indicates that the participant is experiencing more severe fatigue.

Time frame: Baseline, 6-months after start of HPTH, last visit on HPTH (up to 5 years), and post-HPTH follow-up visit (6 months post last visit on HPTH)

Population: Secondary Efficacy Population: This population consists of all participants who received at least one dose of HPTH and had at least one post-baseline non-biopsy efficacy assessment. This population will only include participants in Cohorts 2 and 3.

Participants (Cohorts 2 and 3) were randomized to receive their second bone biopsy at year 1, 2, or 4 after the start of HPTH therapy. Because the sample sizes for the 1-, 2- and 4-year biopsies are reduced due to the early termination of the study, the 2-, and 4-year biopsies were collapsed into one biopsy year group. Ct.Th, measured from the bone biopsy, is the average thickness of the inner and outer cortices. The unit of measure is a z-score. Z-scores are normed to standard populations to a mean of zero and a standard deviation of 1. The normal range for a z-score is from -2 to 2. Values above or below this normal range are considered worse outcomes. The changes in Ct.Th between two time-points are being reported. The n's in the outcome measure table refer to the number of complete records (non-missing baseline and post-baseline measures).

Time frame: Baseline, 1 year bone biopsy, and combined 2 and 4 year bone biopsies

Population: The Bone Biopsy Analysis Population was used for the primary bone biopsy biomarkers. The Bone Biopsy Population consisted of all participants in Cohorts 2 and 3 who completed both their baseline and randomized 1, 2, or 4 year bone biopsies.

Participants (in Cohorts 2 and 3) were randomized to receive their second bone biopsy at year 1, 2, or 4 after the start of HPTH therapy. Because the sample sizes for the 1-, 2- and 4-year biopsies are reduced due to the early termination of the study, the 2-, and 4-year biopsies were collapsed into one biopsy year group. Cn.AjAR is measured from the bone biopsy. Cn.AjAR represents the Cn.MAR averaged over the entire osteoid surface.The unit of measure is a z-score. Z-scores are normed to standard populations to a mean of zero and a standard deviation of 1. The normal range for a z-score is from -2 to 2. Values above or below this normal range are considered worse outcomes. The changes in Cn.AjAR between two time-points are being reported. The n's in the outcome measure table refer to the number of complete records (non-missing baseline and post-baseline measures).

Time frame: Baseline, 1 year bone biopsy, and combined 2 and 4 year bone biopsies

Population: The Bone Biopsy Analysis Population was used for the primary bone biopsy biomarkers. The Bone Biopsy Population consisted of all participants in Cohorts 2 and 3 who completed both their baseline and randomized 1, 2, or 4 year bone biopsies.

Participants (in Cohorts 2 and 3) were randomized to receive their second bone biopsy at year 1, 2, or 4 after the start of HPTH therapy. For Cohort 2, the baseline bone biopsy was completed at the start of CC on the original protocol. For Cohort 3, the baseline biopsy was completed immediately prior to the first HPTH dose. Because the sample sizes for the 1-, 2- and 4-year biopsies are reduced due to the early termination of the study, the 2-, and 4-year biopsies were collapsed into one biopsy year group. Cn.MAR is measured from the bone biopsy. This measures the rate mineral is being laid down per day in a predefined region of the cancellous bone. The unit of measure is a z-score. Z-scores are normed to standard populations to a mean of zero and a standard deviation of 1. The normal range for a z-score is from -2 to 2. Values above or below this normal range are considered worse outcomes. The changes in Cn.MAR between two time-points are being reported.

Time frame: Baseline, 1 year bone biopsy, and combined 2 and 4 year bone biopsies

Population: The Bone Biopsy Analysis Population was used for the primary bone biopsy biomarkers. The Bone Biopsy Population consisted of all participants in Cohorts 2 and 3 who completed both their baseline and randomized 1, 2, or 4 year bone biopsies.

Participants (in Cohorts 2 and 3) were randomized to receive their second bone biopsy at year 1, 2, or 4 after the start of HPTH therapy. For Cohort 2, the baseline bone biopsy was completed at the start of CC on the original protocol. For Cohort 3, the baseline biopsy was completed immediately prior to the first HPTH dose. Because the sample sizes for the 1-, 2- and 4-year biopsies are reduced due to the early termination of the study, the 2-, and 4-year biopsies were collapsed into one biopsy year group. Cn.ES/BS is measured from the bone biopsy. This measure demonstrates the percentage of the cancellous bone surface that contains unmineralized bone (osteoid). The region of interest is the predefined area of total bone that is being measured. The changes in Cn.ES/BS between two time-points are being reported.

Time frame: Baseline, 1 year bone biopsy, and combined 2 and 4 year bone biopsies

Population: The Bone Biopsy Analysis Population was used for the primary bone biopsy biomarkers. The Bone Biopsy Population consisted of all participants in Cohorts 2 and 3 who completed both their baseline and randomized 1, 2, or 4 year bone biopsies.

Participants (in Cohorts 2 and 3) were randomized to receive their second bone biopsy at year 1, 2, or 4 after the start of HPTH therapy. For Cohort 2, the baseline bone biopsy was completed at the start of CC on the original protocol. For Cohort 3, the baseline biopsy was completed immediately prior to the first HPTH dose. Because the sample sizes for the 1-, 2- and 4-year biopsies are reduced due to the early termination of the study, the 2-, and 4-year biopsies were collapsed into one biopsy year group. Cn.OS/BS is measured from the bone biopsy. This measure demonstrates the percentage of the cancellous bone surface that contains unmineralized bone (osteoid). The region of interest is the predefined area of total bone that is being measured. The changes in Cn.OS/BS between two time-points are being reported.

Time frame: Baseline, 1 year bone biopsy, and combined 2 and 4 year bone biopsies

Population: The Bone Biopsy Analysis Population was used for the primary bone biopsy biomarkers. The Bone Biopsy Population consisted of all participants in Cohorts 2 and 3 who completed both their baseline and randomized 1, 2, or 4 year bone biopsies.

Participants (in Cohorts 2 and 3) were randomized to receive their second bone biopsy at year 1, 2, or 4 after the start of HPTH therapy. For Cohort 2, the baseline bone biopsy was completed at the start of CC on the original protocol. For Cohort 3, the baseline biopsy was completed immediately prior to the first HPTH dose. Because the sample sizes for the 1-, 2- and 4-year biopsies are reduced due to the early termination of the study, the 2-, and 4-year biopsies were collapsed into one biopsy year group. Cn.O.Th measured from the bone biopsy. This measures the thickness of the unmineralized bone (osteoid) in a predefined region of cancellous bone. The changes in Cn.O.Th between two time-points are being reported.

Time frame: Baseline, 1 year bone biopsy, and combined 2 and 4 year bone biopsies

Population: The Bone Biopsy Analysis Population was used for the primary bone biopsy biomarkers. The Bone Biopsy Population consisted of all participants in Cohorts 2 and 3 who completed both their baseline and randomized 1, 2, or 4 year bone biopsies.

Participants (in Cohorts 2 and 3) were randomized to receive their second bone biopsy at year 1, 2, or 4 after the start of HPTH therapy. For Cohort 2, the baseline bone biopsy was completed at the start of CC on the original protocol. For Cohort 3, the baseline biopsy was completed immediately prior to the first HPTH dose. Because the sample sizes for the 1-, 2- and 4-year biopsies are reduced due to the early termination of the study, the 2-, and 4-year biopsies were collapsed into one biopsy year group. The Cortex 1 Spectral Calcium High is a measure of the area of high bone cortex 1 mineralization based on the mineralization density distribution (BMDD) from the back-scattered electron imaging scan of the bone biopsies. The changes in Ic.MAR between two time-points are being reported. The n's in the outcome measure table refer to the number of complete records (non-missing baseline and post-baseline measures).

Time frame: Baseline, 1 year bone biopsy, and combined 2 and 4 year bone biopsies

Population: The Bone Biopsy Analysis Population was used for the primary bone biopsy biomarkers. The Bone Biopsy Population consisted of all participants in Cohorts 2 and 3 who completed both their baseline and randomized 1, 2, or 4 year bone biopsies.

Participants (in Cohorts 2 and 3) were randomized to receive their second bone biopsy at year 1, 2, or 4 after the start of HPTH therapy. For Cohort 2, the baseline bone biopsy was completed at the start of CC on the original protocol. For Cohort 3, the baseline biopsy was completed immediately prior to the first HPTH dose. Because the sample sizes for the 1-, 2- and 4-year biopsies are reduced due to the early termination of the study, the 2-, and 4-year biopsies were collapsed into one biopsy year group. The Cortex 1 Spectral Calcium Low is a measure of the area of low bone cortex 1 mineralization based on the mineralization density distribution (BMDD) from the back-scattered electron imaging scan of the bone biopsies. The n's in the outcome measure table refer to the number of complete records (non-missing baseline and post-baseline measures).

Time frame: Baseline, 1 year bone biopsy, and combined 2 and 4 year bone biopsies

Population: The Bone Biopsy Analysis Population was used for the primary bone biopsy biomarkers. The Bone Biopsy Population consisted of all participants in Cohorts 2 and 3 who completed both their baseline and randomized 1, 2, or 4 year bone biopsies.

Participants (in Cohorts 2 and 3) were randomized to receive their second bone biopsy at year 1, 2, or 4 after the start of HPTH therapy. For Cohort 2, the baseline bone biopsy was completed at the start of CC on the original protocol. For Cohort 3, the baseline biopsy was completed immediately prior to the first HPTH dose. Because the sample sizes for the 1-, 2- and 4-year biopsies are reduced due to the early termination of the study, the 2-, and 4-year biopsies were collapsed into one biopsy year group. The Cortex 1 Spectral Calcium Mean is a measure of mean bone calcium content of the bone cortex 1 based on the mineralization density distribution (BMDD) from the back-scattered electron imaging scan of the bone biopsies. The changes in Ic.MAR between two time-points are being reported. The n's in the outcome measure table refer to the number of complete records (non-missing baseline and post-baseline measures).

Time frame: Baseline, 1 year bone biopsy, and combined 2 and 4 year bone biopsies

Population: The Bone Biopsy Analysis Population was used for the primary bone biopsy biomarkers. The Bone Biopsy Population consisted of all participants in Cohorts 2 and 3 who completed both their baseline and randomized 1, 2, or 4 year bone biopsies.

Participants (in Cohorts 2 and 3) were randomized to receive their second bone biopsy at year 1, 2, or 4 after the start of HPTH therapy. For Cohort 2, the baseline bone biopsy was completed at the start of CC on the original protocol. For Cohort 3, the baseline biopsy was completed immediately prior to the first HPTH dose. Because the sample sizes for the 1-, 2- and 4-year biopsies are reduced due to the early termination of the study, the 2-, and 4-year biopsies were collapsed into one biopsy year group. The Cortex 1 Spectral Calcium Peak is a measure of the most frequent calcium content of the bone cortex 1 based on the bone mineralization density distribution (BMDD) from the back-scattered electron imaging scan of the bone biopsies. The changes in Ic.MAR between two time-points are being reported. The n's in the outcome measure table refer to the number of complete records (non-missing baseline and post-baseline measures).

Time frame: Baseline, 1 year bone biopsy, and combined 2 and 4 year bone biopsies

Population: The Bone Biopsy Analysis Population was used for the primary bone biopsy biomarkers. The Bone Biopsy Population consisted of all participants in Cohorts 2 and 3 who completed both their baseline and randomized 1, 2, or 4 year bone biopsies.

Participants (in Cohorts 2 and 3) were randomized to receive their second bone biopsy at year 1, 2, or 4 after the start of HPTH therapy. For Cohort 2, the baseline bone biopsy was completed at the start of CC on the original protocol. For Cohort 3, the baseline biopsy was completed immediately prior to the first HPTH dose. Because the sample sizes for the 1-, 2- and 4-year biopsies are reduced due to the early termination of the study, the 2-, and 4-year biopsies were collapsed into one biopsy year group. The Cortex 1 Spectral Calcium Low is a measure of the area of low bone cortex 1 mineralization based on the mineralization density distribution (BMDD) from the back-scattered electron imaging scan of the bone biopsies. The changes in Ic.MAR between two time-points are being reported. The n's in the outcome measure table refer to the number of complete records (non-missing baseline and post-baseline measures).

Time frame: Baseline, 1 year bone biopsy, and combined 2 and 4 year bone biopsies

Population: The Bone Biopsy Analysis Population was used for the primary bone biopsy biomarkers. The Bone Biopsy Population consisted of all participants in Cohorts 2 and 3 who completed both their baseline and randomized 1, 2, or 4 year bone biopsies.

Participants (in Cohorts 2 and 3) were randomized to receive their second bone biopsy at year 1, 2, or 4 after the start of HPTH therapy. For Cohort 2, the baseline bone biopsy was completed at the start of CC on the original protocol. For Cohort 3, the baseline biopsy was completed immediately prior to the first HPTH dose. Because the sample sizes for the 1-, 2- and 4-year biopsies are reduced due to the early termination of the study, the 2-, and 4-year biopsies were collapsed into one biopsy year group. Ec.AjAR is measured from the bone biopsy. Ec.AjAR represents the endocortical mineral apposition rate (Ec.MAR) averaged over the entire osteoid surface. This is another histomorphometric way to evaluate the rate at which bone is laid down on the inner cortical surface per day. The changes in Ec.AjAR between two time-points are being reported. The n's in the outcome measure table refer to the number of complete records (non-missing baseline and post-baseline measures).

Time frame: Baseline, 1 year bone biopsy, and combined 2 and 4 year bone biopsies

Population: The Bone Biopsy Analysis Population was used for the primary bone biopsy biomarkers. The Bone Biopsy Population consisted of all participants in Cohorts 2 and 3 who completed both their baseline and randomized 1, 2, or 4 year bone biopsies.

Participants (in Cohorts 2 and 3) were randomized to receive their second bone biopsy at year 1, 2, or 4 after the start of HPTH therapy. For Cohort 2, the baseline bone biopsy was completed at the start of CC on the original protocol. For Cohort 3, the baseline biopsy was completed immediately prior to the first HPTH dose.Because the sample sizes for the 1-, 2- and 4-year biopsies are reduced due to the early termination of the study, the 2-, and 4-year biopsies were collapsed into one biopsy year group. Ec.MAR is measured from the bone biopsy. This measures the rate mineral is being laid down per day on the inner cortical (endocortical) surface in a predefined region of cortical bone. The changes in Ec.MAR between two time-points are being reported. The n's in the outcome measure table refer to the number of complete records (non-missing baseline and post-baseline measures).

Time frame: Baseline, 1 year bone biopsy, and combined 2 and 4 year bone biopsies

Population: The Bone Biopsy Analysis Population was used for the primary bone biopsy biomarkers. The Bone Biopsy Population consisted of all participants in Cohorts 2 and 3 who completed both their baseline and randomized 1, 2, or 4 year bone biopsies.

Participants (in Cohorts 2 and 3) were randomized to receive their second bone biopsy at year 1, 2, or 4 after the start of HPTH therapy. For Cohort 2, the baseline bone biopsy was completed at the start of CC on the original protocol. For Cohort 3, the baseline biopsy was completed immediately prior to the first HPTH dose. Because the sample sizes for the 1-, 2- and 4-year biopsies are reduced due to the early termination of the study, the 2-, and 4- year biopsies were collapsed into one biopsy year group. Ec.ES/BS is measured from the bone biopsy. This measure demonstrates the percentage of the endocortical bone surface that is resorbed (eroded). The region of interest is the predefined area of total bone that is being measured. The changes in Ec.ES/BS between two time-points are being reported. The n's in the outcome measure table refer to the number of complete records (non-missing baseline and post-baseline measures).

Time frame: Baseline, 1 year bone biopsy, and combined 2 and 4 year bone biopsies

Population: The Bone Biopsy Analysis Population was used for the primary bone biopsy biomarkers. The Bone Biopsy Population consisted of all participants in Cohorts 2 and 3 who completed both their baseline and randomized 1, 2, or 4 year bone biopsies.

Participants (in Cohorts 2 and 3) were randomized to receive their second bone biopsy at year 1, 2, or 4 after the start of HPTH therapy. For Cohort 2, the baseline bone biopsy was completed at the start of CC on the original protocol. For Cohort 3, the baseline biopsy was completed immediately prior to the first HPTH dose. Because the sample sizes for the 1-, 2- and 4-year biopsies are reduced due to the early termination of the study, the 2-, and 4-year biopsies were collapsed into one biopsy year group. Ec.OS/BS is measured from the bone biopsy. This measures the rate mineral is being laid down per day on the inner cortical (endocortical) surface in a predefined region of cortical bone. The changes in Ec.OS/BS between two time-points are being reported. The n's in the outcome measure table refer to the number of complete records (non-missing baseline and post-baseline measures).

Time frame: Baseline, 1 year bone biopsy, and combined 2 and 4 year bone biopsies

Population: The Bone Biopsy Analysis Population was used for the primary bone biopsy biomarkers. The Bone Biopsy Population consisted of all participants in Cohorts 2 and 3 who completed both their baseline and randomized 1, 2, or 4 year bone biopsies.

Participants (in Cohorts 2 and 3) were randomized to receive their second bone biopsy at year 1, 2, or 4 after the start of HPTH therapy. For Cohort 2, the baseline bone biopsy was completed at the start of CC on the original protocol. For Cohort 3, the baseline biopsy was completed immediately prior to the first HPTH dose. Because the sample sizes for the 1-, 2- and 4-year biopsies are reduced due to the early termination of the study, the 2-, and 4-year biopsies were collapsed into one biopsy year group. Ec.O.Th is measured from the bone biopsy. This measures the thickness of the unmineralized bone (osteoid) on the inner side of the cortex(endocortical). The changes in Cn.AjAR between two time-points are being reported. The n's in the outcome measure table refer to the number of complete records (non-missing baseline and post-baseline measures).

Time frame: Baseline, 1 year bone biopsy, and combined 2 and 4 year bone biopsies

Population: The Bone Biopsy Analysis Population was used for the primary bone biopsy biomarkers. The Bone Biopsy Population consisted of all participants in Cohorts 2 and 3 who completed both their baseline and randomized 1, 2, or 4 year bone biopsies.

Participants (in Cohorts 2 and 3) were randomized to receive their second bone biopsy at year 1, 2, or 4 after the start of HPTH therapy. Because the sample sizes for the 1-, 2- and 4-year biopsies are reduced due to the early termination of the study, the 2-, and 4-year biopsies were collapsed into one biopsy year group. Ic.AjAR is one of 21 secondary endpoints measured from the bone biopsy. Ic.AjAR represents the intracortical mineral apposition rate (Ic.MAR) averaged over the the entire osteoid surface. This is another histomorphometric way to evaluate the rate at which bone is laid down within the middle of the cortex per day. The changes in Ic.AjAR between two time-points are being reported. The n's in the outcome measure table refer to the number of complete records (non-missing baseline and post-baseline values)

Time frame: Baseline, 1 year bone biopsy, and combined 2 and 4 year bone biopsies

Population: The Bone Biopsy Analysis Population was used for the primary bone biopsy biomarkers. The Bone Biopsy Population consisted of all participants in Cohorts 2 and 3 who completed both their baseline and randomized 1, 2, or 4 year bone biopsies.

Participants (in Cohorts 2 and 3) were randomized to receive their second bone biopsy at year 1, 2, or 4 after the start of HPTH therapy. For Cohort 2, the baseline bone biopsy was completed at the start of CC on the original protocol. For Cohort 3, the baseline biopsy was completed immediately prior to the first HPTH dose. Because the sample sizes for the 1-, 2- and 4-year biopsies are reduced due to the early termination of the study, the 2-, and 4-year biopsies were collapsed into one biopsy year group. Ic.MAR is measured from the bone biopsy. This measures the rate mineral is being laid down per day within the middle of the cortex (intracortical) surface in a predefined region of cortical bone. The changes in Ic.MAR between two time-points are being reported. The n's in the outcome measure table refer to the number of complete records (non-missing baseline and post-baseline measures).

Time frame: Baseline, 1 year bone biopsy, and combined 2 and 4 year bone biopsies

Population: The Bone Biopsy Analysis Population was used for the primary bone biopsy biomarkers. The Bone Biopsy Population consisted of all participants in Cohorts 2 and 3 who completed both their baseline and randomized 1, 2, or 4 year bone biopsies.

Participants (in Cohorts 2 and 3) were randomized to receive their second bone biopsy at year 1, 2, or 4 after the start of HPTH therapy. For Cohort 2, the baseline bone biopsy was completed at the start of CC on the original protocol. For Cohort 3, the baseline biopsy was completed immediately prior to the first HPTH dose. Because the sample sizes for the 1-, 2- and 4-year biopsies are reduced due to the early termination of the study, the 2-, and 4-year biopsies were collapsed into one biopsy year group. Ic.ES/BS is measured from the bone biopsy. This measure demonstrates the percentage of bone surface within the middle of the cortex that is resorbed (eroded). The region of interest is the predefined area of total bone that is being measured. The changes in Ic.ES/BS between two time-points are being reported. The n's in the outcome measure table refer to the number of complete records (non-missing baseline and post-baseline measures).

Time frame: Baseline, 1 year bone biopsy, and combined 2 and 4 year bone biopsies

Population: The Bone Biopsy Analysis Population was used for the primary bone biopsy biomarkers. The Bone Biopsy Population consisted of all participants in Cohorts 2 and 3 who completed both their baseline and randomized 1, 2, or 4 year bone biopsies.

Participants (in Cohorts 2 and 3) were randomized to receive their second bone biopsy at year 1, 2, or 4 after the start of HPTH therapy. For Cohort 2, the baseline bone biopsy was completed at the start of CC on the original protocol. For Cohort 3, the baseline biopsy was completed immediately prior to the first HPTH dose. Because the sample sizes for the 1-, 2- and 4-year biopsies are reduced due to the early termination of the study, the 2-, and 4-year biopsies were collapsed into one biopsy year group. Ic.OS/BS measured from the bone biopsy. This measure demonstrates the percentage of the intracortical bone surface that is not mineralized (osteoid). The region of interest is the predefined area of total bone that is being measured. The changes in OS/BS between two time-points are being reported. The n's in the outcome measure table refer to the number of complete records (non-missing baseline and post-baseline measures).

Time frame: Baseline, 1 year bone biopsy, and combined 2 and 4 year bone biopsies

Population: The Bone Biopsy Analysis Population was used for the primary bone biopsy biomarkers. The Bone Biopsy Population consisted of all participants in Cohorts 2 and 3 who completed both their baseline and randomized 1, 2, or 4 year bone biopsies.

Participants (in Cohorts 2 and 3) were randomized to receive their second bone biopsy at year 1, 2, or 4 after the start of HPTH therapy. For Cohort 2, the baseline bone biopsy was completed at the start of CC on the original protocol. For Cohort 3, the baseline biopsy was completed immediately prior to the first HPTH dose. Because the sample sizes for the 1-, 2- and 4-year biopsies are reduced due to the early termination of the study, the 2-, and 4-year biopsies were collapsed into one biopsy year group. Ic.O.Th is one of 21 secondary endpoints measured from the bone biopsy. This measures the thickness of the unmineralized bone (osteoid) within the middle of the cortex (intracortical). The changes in Ic.O.Th between two time-points are being reported. The n's in the outcome measure table refer to the number of complete records (non-missing baseline and post-baseline measures).

Time frame: Baseline, 1 year bone biopsy, and combined 2 and 4 year bone biopsies

Population: The Bone Biopsy Analysis Population was used for the primary bone biopsy biomarkers. The Bone Biopsy Population consisted of all participants in Cohorts 2 and 3 who completed both their baseline and randomized 1, 2, or 4 year bone biopsies.

Following their baseline bone biopsy, 5, 5, and 2 participants were randomized to receive their second bone biopsy at years 1, 2, and 4 after the start of HPTH therapy, respectively. Because the sample sizes for the 1-, 2- and 4-year biopsies are reduced in size due to withdrawal and the early termination of the study, the 2-, and 4-year biopsies were collapsed into one biopsy year group. Ct.Po.Ar is measured from the bone biopsy. This measure defines the area of the cortical bone with holes within a predefined section of cortical bone. The changes in Tb.Sp between two time-points are being reported. The n's in the outcome measure table refer to the number of complete records (non-missing baseline and post-baseline measures).

Time frame: Baseline, 1 year bone biopsy, and combined 2 and 4 year bone biopsies

Population: The Bone Biopsy Analysis Population was used for the primary bone biopsy biomarkers. The Bone Biopsy Population consisted of all participants who completed both their baseline and randomized 1, 2, or 4 year bone biopsies. This will only include participants from cohorts 2 and 3.

Participants (in Cohorts 2 and 3) were randomized to receive their second bone biopsy at year 1, 2, or 4 after the start of HPTH therapy. For Cohort 2, the baseline bone biopsy was completed at the start of CC on the original protocol. For Cohort 3, the baseline biopsy was completed immediately prior to the first HPTH dose. Because the sample sizes for the 1-, 2- and 4-year biopsies are reduced due to the early termination of the study, the 2-, and 4-year biopsies were collapsed into one biopsy year group. Tb.N is measured from the bone biopsy. Tb.N is the measure of the average number of trabeculae per unit length. The unit of measure is a z-score. Z-scores are normed to standard populations to a mean of zero and a standard deviation of 1. The normal range for a z-score is from -2 to 2. Values above or below this normal range are considered worse outcomes. The changes in Tb.N between two time-points are being reported.

Time frame: Baseline, 1 year bone biopsy, and combined 2 and 4 year bone biopsies

Population: The Bone Biopsy Analysis Population was used for the primary bone biopsy biomarkers. The Bone Biopsy Population consisted of all participants in Cohorts 2 and 3 who completed both their baseline and randomized 1, 2, or 4 year bone biopsies.

Participants (in Cohorts 2 and 3) were randomized to receive their second bone biopsy at year 1, 2, or 4 after the start of HPTH therapy. For Cohort 2, the baseline bone biopsy was completed at the start of CC on the original protocol. For Cohort 3, the baseline biopsy was completed immediately prior to the first HPTH dose. Because the sample sizes for the 1-, 2- and 4-year biopsies are reduced due to the early termination of the study, the 2-, and 4-year biopsies were collapsed into one biopsy year group. Tb.Sp is measured from the bone biopsy. Tb.Sp is the mean distance between trabeculae, assessed using direct 3D methods. The unit of measure is a z-score. Z-scores are normed to standard populations to a mean of zero and a standard deviation of 1. The normal range for a z-score is from -2 to 2. Values above or below this normal range are considered worse outcomes. The changes in Tb.Sp between two time-points are being reported.

Time frame: Baseline, 1 year bone biopsy, and combined 2 and 4 year bone biopsies

Population: The Bone Biopsy Analysis Population was used for the primary bone biopsy biomarkers. The Bone Biopsy Population consisted of all participants in Cohorts 2 and 3 who completed both their baseline and randomized 1, 2, or 4 year bone biopsies.

Participants (in Cohorts 2 and 3) were randomized to receive their second bone biopsy at year 1, 2, or 4 after the start of HPTH therapy. For Cohort 2, the baseline bone biopsy was completed at the start of CC on the original protocol. For Cohort 3, the baseline biopsy was completed immediately prior to the first HPTH dose. Because the sample sizes for the 1-, 2- and 4-year biopsies are reduced due to the early termination of the study, the 2-, and 4-year biopsies were collapsed into one biopsy year group. Tb.Th is measured from the bone biopsy. Tb.Th is the mean thickness of trabeculae, assessed using direct 3D methods. The unit of measure is a z-score. Z-scores are normed to standard populations to a mean of zero and a standard deviation of 1. The normal range for a z-score is from -2 to 2. Values above or below this normal range are considered worse outcomes. The changes in Tb.Th between two time-points are being reported.

Time frame: Baseline, 1 year bone biopsy, and combined 2 and 4 year bone biopsies

Population: The Bone Biopsy Analysis Population was used for the primary bone biopsy biomarkers. The Bone Biopsy Population consisted of all participants in Cohorts 2 and 3 who completed both their baseline and randomized 1, 2, or 4 year bone biopsies.

Severity is measured using four separate items of the FSI questionnaire that assesses how the participant felt on their most, least, and average fatigue days in the past week as well as current fatigue. Participants score their level of fatigue for each item on an 11-point scale (0=not at all fatigued, 10=as fatigued as I could be). The composite severity score reflects the sum of these 4 scores. The composite severity scores can range from 0 to 40. A higher composite severity scores indicates that the participant is experiencing more severe fatigue.

Time frame: Baseline, 6-months after start of HPTH, last visit on HPTH (up to 5 years), and post-HPTH follow-up visit (6 months post last visit on HPTH)

Population: Secondary Efficacy Population: This population consists of all participants who received at least one dose of HPTH and had at least one post-baseline non-biopsy efficacy assessment. This population will only include participants in Cohorts 2 and 3.

Participants had ultrasound and CT imaging of the kidney were performed yearly. The rates of new, stable, and progressing nephrocalcinosis and nephrolithiasis (NCNL) were recorded.

Time frame: Baseline, 12-Month Visit, 24-Month Visit, 36-Month Visit, 48-Month Visit, and 60-Month Visit

Population: Secondary Efficacy Population: This population consists of all participants who received at least one dose of HPTH and had at least one post-baseline non-biopsy efficacy assessment. This population will only include participants in Cohorts 2 and 3.

Perceived interference is measured using seven separate items that assess the degree to which fatigue in the past week was judged to interfere with general level of activity, ability to bathe and dress, normal work activity, ability to concentrate, relations with others, enjoyment of life, and mood. The interference ratings were summed to yield a total interference score ranging from 0 (no perceived interference due to fatigue) to 70 (maximum possible perceived interference due to fatigue).

Time frame: Baseline, 6-months after start of HPTH, last visit on HPTH (up to 5 years), and post-HPTH follow-up visit (6 months post last visit on HPTH)

Population: Secondary Efficacy Population: This population consists of all participants who received at least one dose of HPTH and had at least one post-baseline non-biopsy efficacy assessment. This population will only include participants in Cohorts 2 and 3.

The 8 primary bone biopsy measures were to be adjusted HPTH dose by fitting the primary bone biopsy model with both linear and quadratic dose covariates added to the model. However, the study was terminated early resulting in only 5, 5, and 2 participants having their biopsies at 1, 2, and 4 years respectively. To add additional linear and quadratic dose covariates to the statistical model with an already small sample sizes would highly risk over-parameterizing the model. Thus no new analysis was performed.

Time frame: Baseline, 1 year bone biopsy, and combined 2 and 4 year bone biopsies

Population: The Bone Biopsy Analysis Population was used for the primary bone biopsy biomarkers. The Bone Biopsy Population consisted of all participants in Cohorts 2 and 3 who completed both their baseline and randomized 1, 2, or 4 year bone biopsies.

The DXA BMD measures were assessed every 6 months over 5 years, and at a follow-up visit post-HPTH therapy. Due to varying lengths of time on each participant was on HPTH, these BMD assessment times were collapsed for purposes of analysis to: baseline, 6-month on HPTH therapy, last visit on HPTH therapy, and the post-HPTH follow-up visit The 1/3 Radius BMD is one of 6 bone regions measurements of bone mineralization density assessed by DXA.

Time frame: Baseline, 6-months after start of HPTH, last visit on HPTH (up to 5 years), and post-HPTH follow-up visit (6 months post last visit on HPTH)

Population: Secondary Efficacy Population: This population consists of all participants who received at least one dose of HPTH and had at least one post-baseline non-biopsy efficacy assessment. This population will only include participants in Cohorts 2 and 3.

The DXA BMD were assessed every 6 months over 5 years, and at a follow-up visit post-HPTH therapy. Due to varying lengths of time on each participant was on HPTH, these BMD assessment times were collapsed for purposes of analysis to: baseline, 6-month on HPTH therapy, last visit on HPTH therapy, and the post-HPTH follow-up visit. The AP Spine BMD is one of 6 bone regions measurements of bone mineralization density assessed by DXA.

Time frame: Baseline, 6-months after start of HPTH, last visit on HPTH (up to 5 years), and post-HPTH follow-up visit (6 months post last visit on HPTH)

Population: Secondary Efficacy Population: This population consists of all participants who received at least one dose of HPTH and had at least one post-baseline non-biopsy efficacy assessment. This population will only include participants in Cohorts 2 and 3.

The DXA BMD measures were assessed every 6 months over 5 years, and at a follow-up visit post-HPTH therapy. Due to varying lengths of time on each participant was on HPTH, these BMD assessment times were collapsed for purposes of analysis to: baseline, 6-month on HPTH therapy, last visit on HPTH therapy, and the post-HPTH follow-up visit. The Femoral BMD is one of 6 bone regions measurements of bone mineralization density assessed by DXA.

Time frame: Baseline, 6-months after start of HPTH, last visit on HPTH (up to 5 years), and post-HPTH follow-up visit (6 months post last visit on HPTH)

Population: Secondary Efficacy Population: This population consists of all participants who received at least one dose of HPTH and had at least one post-baseline non-biopsy efficacy assessment. This population will only include participants in Cohorts 2 and 3.

The DXA BMD were assessed every 6 months over 5 years, and at a follow-up visit post-HPTH therapy. Due to varying lengths of time on each participant was on HPTH, these BMD assessment times were collapsed for purposes of analysis to: baseline, 6-month on HPTH therapy, last visit on HPTH therapy, and the post-HPTH follow-up visit. The Lateral Spine BMD is one of 6 bone regions measurements of bone mineralization density assessed by DXA .

Time frame: Baseline, 6-months after start of HPTH, last visit on HPTH (up to 5 years), and post-HPTH follow-up visit (6 months post last visit on HPTH)

Population: Secondary Efficacy Population: This population consists of all participants who received at least one dose of HPTH and had at least one post-baseline non-biopsy efficacy assessment. This population will only include participants in Cohorts 2 and 3.

The DXA BMD measures were assessed every 6 months over 5 years, and at a follow-up visit post-HPTH therapy. Due to varying lengths of time on each participant was on HPTH, these BMD assessment times were collapsed for purposes of analysis to: baseline, 6-month on HPTH therapy, last visit on HPTH therapy, and the post-HPTH follow-up visit. The Total Hip BMD is one of 6 bone regions measurements of bone mineralization density assessed by DXA.

Time frame: Baseline, 6-months after start of HPTH, last visit on HPTH (up to 5 years), and post-HPTH follow-up visit (6 months post last visit on HPTH)

Population: Secondary Efficacy Population: This population consists of all participants who received at least one dose of HPTH and had at least one post-baseline non-biopsy efficacy assessment. This population will only include participants in Cohorts 2 and 3.

The DXA BMD measures were assessed every 6 months over 5 years, and at a follow-up visit post-HPTH therapy. Due to varying lengths of time on each participant was on HPTH, these BMD assessment times were collapsed for purposes of analysis to: baseline, 6-month on HPTH therapy, last visit on HPTH therapy, and the post-HPTH follow-up visit. The Whole Body BMD is one of 6 bone regions measurements of bone mineralization density assessed by DXA.

Time frame: Baseline, 6-months after start of HPTH, last visit on HPTH (up to 5 years), and post-HPTH follow-up visit (6 months post last visit on HPTH)

Population: Secondary Efficacy Population: This population consists of all participants who received at least one dose of HPTH and had at least one post-baseline non-biopsy efficacy assessment. This population will only include participants in Cohorts 2 and 3.

As a sensitivity analysis, the 8 primary bone biopsy measures were to be adjusted for female menopausal status, by fitting the primary bone biopsy model with a menopausal status covariate added to the model. However, the study was terminated early resulting in only 5, 5, and 2 participants having their biopsies at 1, 2, and 4 years respectively. Furthermore, 3 males would need to be removed from the model leaving 4, 3, 2 participants with bone biopsies with an additional degree of freedom consumed for the menopausal status covariate. Thus, the planned mixed models analysis was not performed since with such small samples sizes random fluctuations in the data could give misleading erroneous results.

Time frame: Baseline, 1 year bone biopsy, and combined 2 and 4 year bone biopsies

Population: The Bone Biopsy Analysis Population was used for the primary bone biopsy biomarkers. The Bone Biopsy Population consisted of all participants in Cohorts 2 and 3 who completed both their baseline and randomized 1, 2, or 4 year bone biopsies.

Serum Alkaline Phosphatase concentration

Time frame: Baseline, last visit on HPTH (up to 5 years), and post-HPTH follow-up visit (6 months post last visit on HPTH)

Population: Secondary Efficacy Population: This population consists of all participants who received at least one dose of HPTH and had at least one post-baseline non-biopsy efficacy assessment. This population will only include participants in Cohorts 2 and 3.

Serum Calcium concentration

Time frame: Baseline, last visit on HPTH (up to 5 years), and post-HPTH follow-up visit (6 months post last visit on HPTH)

Population: Secondary Efficacy Population: This population consists of all participants who received at least one dose of HPTH and had at least one post-baseline non-biopsy efficacy assessment. This population will only include participants in Cohorts 2 and 3.

Serum Osteocalcin concentration

Time frame: Baseline, last visit on HPTH (up to 5 years), and post-HPTH follow-up visit (6 months post last visit on HPTH)

Population: Secondary Efficacy Population: This population consists of all participants who received at least one dose of HPTH and had at least one post-baseline non-biopsy efficacy assessment. This population will only include participants in Cohorts 2 and 3.

Serum Phosphorus concentration

Time frame: Baseline, last visit on HPTH (up to 5 years), and post-HPTH follow-up visit (6 months post last visit on HPTH)

Population: Secondary Efficacy Population: This population consists of all participants who received at least one dose of HPTH and had at least one post-baseline non-biopsy efficacy assessment. This population will only include participants in Cohorts 2 and 3.

The Bodily Pain (BP) domain scores are derived from the SF36 Health Survey taken by the participant. The SF-36 is a validated questionnaire assessing 4 physical domains: physical function, physical role limitations, bodily pain, and general health, and 4 mental domains: vitality, emotional role limitations, social function and mental health. From the 36 questions asked, a scoring tool derives SF36 domain scores for each of the eight domains. These domain scores are scaled to range from 0 to 100 with a population mean of 50 and a standard deviation of 10. Lower scores indicate more disability; and, higher scores indicate less disability. The BP domain scores indicate to what extent a participant's bodily pain hinders their performance of daily activities.

Time frame: Baseline, 6-months after start of HPTH, last visit on HPTH (up to 5 years), and post-HPTH follow-up visit (6 months post last visit on HPTH)

Population: Secondary Efficacy Population: This population consists of all participants who received at least one dose of HPTH and had at least one post-baseline non-biopsy efficacy assessment. This population will only include participants in Cohorts 2 and 3.

Emotional Role Limitations (RE) Domain scores are derived from the SF36 Health Survey taken by the participant. The SF-36 is a validated questionnaire assessing 4 physical domains: physical function, physical role limitations, bodily pain, and general health, and 4 mental domains: vitality, emotional role limitations, social function and mental health. From the 36 questions asked, a scoring tool derives SF36 domain scores for each of the eight domains. These domain scores are scaled to range from 0 to 100 with a population mean of 50 and a standard deviation of 10. Lower scores indicate more disability; and, higher scores indicate less disability. The RE Domain score assesses the extent to which the emotional condition of the participant, e.g. feeling depressed or anxious, limits his/her daily functioning and ability to perform roles, such as in cutting down on the amount of time spent on work or other activities and accomplishing less than he/she would like to.

Time frame: Baseline, 6-months after start of HPTH, last visit on HPTH (up to 5 years), and post-HPTH follow-up visit (6 months post last visit on HPTH)

Population: Secondary Efficacy Population: This population consists of all participants who received at least one dose of HPTH and had at least one post-baseline non-biopsy efficacy assessment. This population will only include participants in Cohorts 2 and 3.

General Health (GH) Domain scores are derived from the SF36 Health Survey taken by the participant. The SF-36 is a validated questionnaire assessing 4 physical domains: physical function, physical role limitations, bodily pain, and general health, and 4 mental domains: vitality, emotional role limitations, social function and mental health. From the 36 questions asked, a scoring tool derives SF36 domain scores for each of the eight domains. These domain scores are scaled to range from 0 to 100 with a population mean of 50 and a standard deviation of 10. Lower scores indicate more disability; and, higher scores indicate less disability. The GH domain score assesses a participant's perception of their general health in terms of concepts such as excellent, very good, good, fair or poor, getting ill easier than other people, and just as healthy as anyone he/she knows.

Time frame: Baseline, 6-months after start of HPTH, last visit on HPTH (up to 5 years), and post-HPTH follow-up visit (6 months post last visit on HPTH)

Population: Secondary Efficacy Population: This population consists of all participants who received at least one dose of HPTH and had at least one post-baseline non-biopsy efficacy assessment. This population will only include participants in Cohorts 2 and 3.

Mental Health (MH) Domain scores are derived from the SF36 Health Survey taken by the participant. The SF-36 is a validated questionnaire assessing 4 physical domains: physical function, physical role limitations, bodily pain, and general health, and 4 mental domains: vitality, emotional role limitations, social function and mental health. From the 36 questions asked, a scoring tool derives SF36 domain scores for each of the eight domains. These domain scores are scaled to range from 0 to 100 with a population mean of 50 and a standard deviation of 10. Lower scores indicate more disability; and, higher scores indicate less disability. The MH domain assesses the extent to which the participant is, among other things, feeling full of pep, is happy, is feeling calm and peaceful, is very nervous, or is feeling worn out and tired.

Time frame: Baseline, 6-months after start of HPTH, last visit on HPTH (up to 5 years), and post-HPTH follow-up visit (6 months post last visit on HPTH)

Population: Secondary Efficacy Population: This population consists of all participants who received at least one dose of HPTH and had at least one post-baseline non-biopsy efficacy assessment. This population will only include participants in Cohorts 2 and 3.

Physical Function (PF) Domain scores are derived from the SF36 Health Survey taken by the participant. The SF-36 is a validated questionnaire assessing 4 physical domains: physical function, physical role limitations, bodily pain, and general health, and 4 mental domains: vitality, emotional role limitations, social function and mental health. From the 36 questions asked, a scoring tool derives SF36 domain scores for each of the eight domains. These domain scores are scaled to range from 0 to 100 with a population mean of 50 and a standard deviation of 10. Lower scores indicate more disability; and, higher scores indicate less disability. The PF domain assesses the extent to which the participant's perceptions of his/her ability to perform vigorous and moderate physical activities are influenced by his/her physical condition.

Time frame: Baseline, 6-months after start of HPTH, last visit on HPTH (up to 5 years), and post-HPTH follow-up visit (6 months post last visit on HPTH)

Population: Secondary Efficacy Population: This population consists of all participants who received at least one dose of HPTH and had at least one post-baseline non-biopsy efficacy assessment. This population will only include participants in Cohorts 2 and 3.

Physical Role Limitations (RP) Domain scores are derived from the SF36 Health Survey taken by the participant. The SF-36 is a validated questionnaire assessing 4 physical domains: physical function, physical role limitations, bodily pain, and general health, and 4 mental domains: vitality, emotional role limitations, social function and mental health. From the 36 questions asked, a scoring tool derives SF36 domain scores for each of the eight domains. These domain scores are scaled to range from 0 to 100 with a population mean of 50 and a standard deviation of 10. Lower scores indicate more disability; and, higher scores indicate less disability. The RP Domain assesses the extent to which a participant's' performance of his/her roles in daily activities is impeded by his/her physical state of health.

Time frame: Baseline, 6-months after start of HPTH, last visit on HPTH (up to 5 years), and post-HPTH follow-up visit (6 months post last visit on HPTH)

Population: Secondary Efficacy Population: This population consists of all participants who received at least one dose of HPTH and had at least one post-baseline non-biopsy efficacy assessment. This population will only include participants in Cohorts 2 and 3.

Social Function (SF) Domain scores are derived from the SF36 Health Survey taken by the participant. The SF-36 is a validated questionnaire assessing 4 physical components: physical function, physical role limitations, bodily pain, and general health, and 4 mental components: vitality, emotional role limitations, social function and mental health. From the 36 questions asked, a scoring tool is used to calculate each of the eight domain scores. The scoring tool transforms the score into a 0-100 scale on the assumption that each question carries equal weight. SF36 domain scores are scaled to have a population mean of 50 and a standard deviation of 10. The SF Domain assesses the level of a participant's social activities and interaction with significant others such as family members, friends, neighbours and other social relations. Lower scores indicate more disability; higher scores indicate less disability with respect to social function.

Time frame: Baseline, 6-months after start of HPTH, last visit on HPTH (up to 5 years), and post-HPTH follow-up visit (6 months post last visit on HPTH)

Population: Secondary Efficacy Population: This population consists of all participants who received at least one dose of HPTH and had at least one post-baseline non-biopsy efficacy assessment. This population will only include participants in Cohorts 2 and 3.

Vitality (VT) Domain scores are derived from the SF36 Health Survey taken by the participant. SF36 domain scores are scaled to have a population mean of 50 and a standard deviation of 10. Higher scores reflect a better quality of life.The SF-36 is a validated questionnaire assessing 4 physical components: physical function, physical role limitations, bodily pain, and general health, and 4 mental components: vitality, emotional role limitations, social function and mental health. From the 36 questions asked, a scoring tool is used to calculate the eight domain scores. The scoring tool transforms the score into a 0-100 scale on the assumption that each question carries equal weight. SF36 domain scores are scaled to have a population mean of 50 and a standard deviation of 10. Lower scores indicate more disability; and, higher scores indicate less disability. The VT Domain assesses the participant's experience of feeling energetic and full of pep, or worn out and tired.

Time frame: Baseline, 6-months after start of HPTH, last visit on HPTH (up to 5 years), and post-HPTH follow-up visit (6 months post last visit on HPTH)

Population: Secondary Efficacy Population: This population consists of all participants who received at least one dose of HPTH and had at least one post-baseline non-biopsy efficacy assessment. This population will only include participants in Cohorts 2 and 3.

Participants (in Cohorts 2 and 3) were randomized to receive their second bone biopsy at year 1, 2, or 4 after the start of HPTH therapy. For Cohort 2, the baseline bone biopsy was completed at the start of CC on the original protocol. For Cohort 3, the baseline biopsy was completed immediately prior to the first HPTH dose. Because the sample sizes for the 1-, 2- and 4-year biopsies are reduced due to the early termination of the study, the 2-, and 4-year biopsies were collapsed into one biopsy year group. Ct.AR is measured from the bone biopsy. This measure defines the area of the outer cortex and inner cortex within a predefined section of cortical bone. The changes in Ct.Ar between two time-points are being reported. The n's in the outcome measure table refer to the number of complete records (non-missing baseline and post-baseline measures).

Time frame: Baseline, 1 year bone biopsy, and combined 2 and 4 year bone biopsies

Population: The Bone Biopsy Analysis Population was used for the primary bone biopsy biomarkers. The Bone Biopsy Population consisted of all participants in Cohorts 2 and 3 who completed both their baseline and randomized 1, 2, or 4 year bone biopsies.

The total distance a participant was able to walk during a 6-minute walk

Time frame: Baseline, 6-months after start of HPTH, last visit on HPTH (up to 5 years), and post-HPTH follow-up visit (6 months post last visit on HPTH)

Population: Secondary Efficacy Population: This population consists of all participants who received at least one dose of HPTH and had at least one post-baseline non-biopsy efficacy assessment. This population will only include participants in Cohorts 2 and 3.

The DXA BMD measures were assessed every 6 months over 5 years, and at a follow-up visit post-HPTH therapy. Due to varying lengths of time on each participant was on HPTH, these BMD assessment times were collapsed for purposes of analysis to: baseline, 6-month on HPTH therapy, last visit on HPTH therapy, and the post-HPTH follow-up visit The 1/3 Radius BMD is one of 6 bone regions measurements of bone mineralization density assessed by DXA. The unit of measure is a z-score. Z-scores are normed to standard populations to a mean of zero and a standard deviation of 1. The normal range for a z-score is from -2 to 2. Values above or below this normal range are considered worse outcomes.

Time frame: Baseline, 6-months after start of HPTH, last visit on HPTH (up to 5 years), and post-HPTH follow-up visit (6 months post last visit on HPTH)

Population: Secondary Efficacy Population: This population consists of all participants who received at least one dose of HPTH and had at least one post-baseline non-biopsy efficacy assessment. This population will only include participants in Cohorts 2 and 3.

The DXA BMD were assessed every 6 months over 5 years, and at a follow-up visit post-HPTH therapy. Due to varying lengths of time on each participant was on HPTH, these BMD assessment times were collapsed for purposes of analysis to: baseline, 6-month on HPTH therapy, last visit on HPTH therapy, and the post-HPTH follow-up visit. The AP Spine BMD is one of 6 bone regions measurements of bone mineralization density assessed by DXA. The unit of measure is a z-score. Z-scores are normed to standard populations to a mean of zero and a standard deviation of 1. The normal range for a z-score is from -2 to 2. Values above or below this normal range are considered worse outcomes.

Time frame: Baseline, 6-months after start of HPTH, last visit on HPTH, and post-HPTH follow-up visits

Population: Secondary Efficacy Population: This population consists of all participants who received at least one dose of HPTH and had at least one post-baseline non-biopsy efficacy assessment. This population will only include participants in Cohorts 2 and 3.

The DXA BMD measures were assessed every 6 months over 5 years, and at a follow-up visit post-HPTH therapy. Due to varying lengths of time on each participant was on HPTH, these BMD assessment times were collapsed for purposes of analysis to: baseline, 6-month on HPTH therapy, last visit on HPTH therapy, and the post-HPTH follow-up visit. The Femoral BMD is one of 6 bone regions measurements of bone mineralization density assessed by DXA. The unit of measure is a z-score. Z-scores are normed to standard populations to a mean of zero and a standard deviation of 1. The normal range for a z-score is from -2 to 2. Values above or below this normal range are considered worse outcomes.

Time frame: Baseline, 6-months after start of HPTH, last visit on HPTH, and post-HPTH follow-up visits

Population: Secondary Efficacy Population: This population consists of all participants who received at least one dose of HPTH and had at least one post-baseline non-biopsy efficacy assessment. This population will only include participants in Cohorts 2 and 3.

The DXA BMD were assessed every 6 months over 5 years, and at a follow-up visit post-HPTH therapy. Due to varying lengths of time on each participant was on HPTH, these BMD assessment times were collapsed for purposes of analysis to: baseline, 6-month on HPTH therapy, last visit on HPTH therapy, and the post-HPTH follow-up visit. The Lateral Spine BMD is one of 6 bone regions measurements of bone mineralization density assessed by DXA . The unit of measure is a z-score. Z-scores are normed to standard populations to a mean of zero and a standard deviation of 1. The normal range for a z-score is from -2 to 2. Values above or below this normal range are considered worse outcomes.

Time frame: Baseline, 6-months after start of HPTH, last visit on HPTH, and post-HPTH follow-up visits

Population: Secondary Efficacy Population: This population consists of all participants who received at least one dose of HPTH and had at least one post-baseline non-biopsy efficacy assessment. This population will only include participants in Cohorts 2 and 3.

The DXA BMD measures were assessed every 6 months over 5 years, and at a follow-up visit post-HPTH therapy. Due to varying lengths of time on each participant was on HPTH, these BMD assessment times were collapsed for purposes of analysis to: baseline, 6-month on HPTH therapy, last visit on HPTH therapy, and the post-HPTH follow-up visit. The Total Hip BMD is one of 6 bone regions measurements of bone mineralization density assessed by DXA. The unit of measure is a z-score. Z-scores are normed to standard populations to a mean of zero and a standard deviation of 1. The normal range for a z-score is from -2 to 2. Values above or below this normal range are considered worse outcomes.

Time frame: Baseline, 6-months after start of HPTH, last visit on HPTH, and post-HPTH follow-up visits

Population: Secondary Efficacy Population: This population consists of all participants who received at least one dose of HPTH and had at least one post-baseline non-biopsy efficacy assessment. This population will only include participants in Cohorts 2 and 3.

The DXA BMD measures were assessed every 6 months over 5 years, and at a follow-up visit post-HPTH therapy. Due to varying lengths of time on each participant was on HPTH, these BMD assessment times were collapsed for purposes of analysis to: baseline, 6-month on HPTH therapy, last visit on HPTH therapy, and the post-HPTH follow-up visit. The Whole Body BMD is one of 6 bone regions measurements of bone mineralization density assessed by DXA. The unit of measure is a z-score. Z-scores are normed to standard populations to a mean of zero and a standard deviation of 1. The normal range for a z-score is from -2 to 2. Values above or below this normal range are considered worse outcomes.

Time frame: Baseline, 6-months after start of HPTH, last visit on HPTH, and post-HPTH follow-up visits

Population: Secondary Efficacy Population: This population consists of all participants who received at least one dose of HPTH and had at least one post-baseline non-biopsy efficacy assessment. This population will only include participants in Cohorts 2 and 3.