Parathyroid Hormone (PTH) for Osteoporosis in Postmenopausal Women

Study Overview
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Brief Summary
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Parathyroid hormone (PTH) increases bone formation and thereby improves bone density and bone strength in postmenopausal women with osteoporosis. However, prolonged PTH treatment increases bone formation less and less over time. This study will test whether increasing the daily dose of PTH sustains its ability to improve bone formation, and optional sub-studies will test several potential reasons why PTH's effects on bone formation decline over time.

Detailed Description
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In women with postmenopausal osteoporosis, PTH increases bone mineral density more than anti-resorptive agents, and its use markedly reduces the incidence of new spine and non-spine fractures. Still, PTH is not a cure for osteoporosis in many patients because PTH-stimulated bone formation declines as PTH therapy continues. Biochemical analyses suggest that bone formation and resorption peak after 6 to 9 months of daily PTH therapy and then decline progressively. The study will last 18 months. Blood, urine, and bone density tests will occur at screening. At the start of the study, participants will be randomly assigned to one of two PTH dose regimens. Patients will go to Massachusetts General Hospital at Months 0, 3, 6, 9, 12, 15, and 18 for blood and urine collection. In addition, bone density tests by DXA will be performed at Months 0, 6, 12, and 18, and by quantitative CT scans at Months 0 and 18. Approximately 6 weeks after any change in PTH dose, each participant's blood calcium will be checked 4 to 6 hours after that day's PTH injection, and her 24-hour urine calcium excretion will also be checked. Participants may enroll in optional substudies that will test whether reduced skeletal responses to long-term treatment with PTH are accompanied by changes in its absorption and/or destruction and whether reduced skeletal responses to long-term treatment with PTH are accompanied by parallel reductions in kidney responses to PTH.

Official Title
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Evaluation of Factors That Affect Skeletal Responses to PTH

Conditions
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Postmenopausal Osteoporosis, Osteoporosis

Intervention / Treatment
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* Drug: synthetic hPTH 1-34


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Three or more years after menopause Bone mineral density T-score < or = -2.0 by dual-energy x-ray absorptiometry (DXA) of vertebrae or femoral neck, or by quantitative computerized tomography (QCT) of vertebral body trabeculae Exclusion Criteria: Cannot walk without assistance Significant heart, kidney, liver, or malignant disease Current alcohol abuse Major psychiatric disorders Other current or past disorders known to affect bone Use of medications known to affect bone for > 7 days in the past 12 months Use of bisphosphonates or fluoride Abnormal blood calcium, PTH, 25-hydroxy vitamin D, creatinine, liver function tests, or complete blood count Elevated calcium levels in 24-hour urine collection

Ages Eligible for Study
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Minimum Age: 46 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: constant dose<br>Participants will receive synthetic human parathyroid hormone fragment 1-34 (hPTH 1-34) once-daily in a constant dose of 30 mcg/day. | Drug: synthetic hPTH 1-34<br>* Either daily treatment with self-injected hPTH 1-34 or ascending dose treatment at 6-month intervals of hPTH 1-34<br>* Other names: synthetic human parathyroid hormone 1-34;|
| Experimental: ascending dose<br>Participants will receive synthetic human parathyroid hormone fragment 1-34 (hPTH 1-34) once-daily in a dose that ascends at 6 month intervals (20-30-40 mcg/day). | Drug: synthetic hPTH 1-34<br>* Either daily treatment with self-injected hPTH 1-34 or ascending dose treatment at 6-month intervals of hPTH 1-34<br>* Other names: synthetic human parathyroid hormone 1-34;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in Indices of Bone Turnover | Change from month 0 (pre-treatment) baseline serum aminoterminal propeptide of type I collagen (PINP), osteocalcin (OC), and C-terminal telopeptide (CTX), expressed as an area under the curve (AUC). Each marker measurement result was multiplied by the corresponding subject-specific elapsed study time interval using the trapezoidal rule, and these products were summed to generate a subject-specific AUC (months*ng/ml) for the marker. | Each index of bone turnover was measured at study month 0, 1.5, 3, 6, 7.5, 9, 12, 13.5, 15, and 18. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Bone Mineral Density (BMD) | Percent change in BMD of the spine, femur, radius, and ulna, and subtotal body, calculated as 100*[(final - month 0)/month 0] in subjects who took study therapy for at least 12 months. | baseline and 18 months (12 months in 4 subjects) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Osteoporosis, Parathyroid hormone, Teriparatide, Bone formation, Bone resorption