Parathyroid Hormone (PTH) for Osteoporosis in Postmenopausal Women

Phase 2

Completed

Brief Summary: 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: 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.

Recruitment & Eligibility

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

Arm && Interventions

Group	Intervention	Description
constant dose	synthetic hPTH 1-34	Participants will receive synthetic human parathyroid hormone fragment 1-34 (hPTH 1-34) once-daily in a constant dose of 30 mcg/day.
ascending dose	synthetic hPTH 1-34	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).

Primary Outcome Measures

Name	Time	Method
Changes in Indices of Bone Turnover	Each index of bone turnover was measured at study month 0, 1.5, 3, 6, 7.5, 9, 12, 13.5, 15, and 18.	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.

Secondary Outcome Measures

Name	Time	Method
Change in Bone Mineral Density (BMD)	baseline and 18 months (12 months in 4 subjects)	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.