Conditions: Postmenopausal Osteoporosis Osteoporosis
Keywords: Osteoporosis Parathyroid hormone Teriparatide Bone formation Bone resorption
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 80
Healthy volunteers: no

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.

Arms:
arm 1: Participants will receive synthetic human parathyroid hormone fragment 1-34 (hPTH 1-34) once-daily in a constant dose of 30 mcg/day. arm 2: 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).

Interventions: intervention 1: synthetic hPTH 1-34
Intervention descriptions: intervention 1: Either daily treatment with self-injected hPTH 1-34 or ascending dose treatment at 6-month intervals of hPTH 1-34

Protocol document: