Clinical trial NCT00086619: Parathyroid Hormone (PTH) for Osteoporosis in Postmenopausal Women
Official title: Evaluation of Factors That Affect Skeletal Responses to PTH
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Postmenopausal Osteoporosis
Osteoporosis
Keywords: Osteoporosis
Parathyroid hormone
Teriparatide
Bone formation
Bone resorption
Lead sponsor: Massachusetts General Hospital
Sponsor class: OTHER
Collaborators: name: National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
First posted: 2004-07-08
Enrollment: 80
Sex: FEMALE
Minimum age (years): 46
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Changes in Indices of Bone Turnover
timeFrame: 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 outcomes:
measure: Change in Bone Mineral Density (BMD)
timeFrame: baseline and 18 months (12 months in 4 subjects)
Other outcomes:
Locations:
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
Study officials:
affiliation: Massachusetts General Hospital
name: Robert M. Neer, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Massachusetts General Hospital
name: Joel S. Finkelstein, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Yu EW, Neer RM, Lee H, Wyland JJ, de la Paz AV, Davis MC, Okazaki M, Finkelstein JS. Time-dependent changes in skeletal response to teriparatide: escalating vs. constant dose teriparatide (PTH 1-34) in osteoporotic women. Bone. 2011 Apr 1;48(4):713-9. doi: 10.1016/j.bone.2010.11.012. Epub 2010 Nov 24.