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
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.
- Three or more years after menopause
- Spine or femoral neck bone density T-score less than -2.0
- Cannot walk without assistance
- Significant heart, kidney, liver, or malignant disease
- Current alcohol abuse
- Major psychiatric disorders
- Current disorders known to affect bone
- Use of medications known to affect bone for more than 7 days in the past 12 months
- Use of bisphosphonates or fluoride
- Abnormal blood calcium, creatinine, liver function tests, or complete blood count
- Elevated calcium levels in 24-hour urine test