Parathyroid Hormone (PTH) for Osteoporosis in Postmenopausal Women

Mass General Brigham

Status and phase: Completed; Phase 2

Conditions: Osteoporosis; Postmenopausal Osteoporosis

Treatments: Drug: synthetic hPTH 1-34

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT00086619

NIAMS-123

1P50AR044855 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 80 patients

Sex: Female

Ages: 46 to 85 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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80 participants in 2 patient groups

constant dose

Experimental group

Description:

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

Treatment:

Drug: synthetic hPTH 1-34

ascending dose

Experimental group

Description:

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).

Treatment:

Drug: synthetic hPTH 1-34