Clinical trial NCT00697463: Forteo for the Treatment of Unexplained Osteoporosis in Premenopausal Women
Official title: Teriparatide for the Treatment of Idiopathic Osteoporosis in Premenopausal Women
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Menopause
Fracture
Osteoporosis
Keywords: Teriparatide
Forteo
Osteopenia
Osteoporosis
Fracture
Low Bone Density
Premenopausal women
Lead sponsor: Columbia University
Sponsor class: OTHER
Collaborators: name: Eli Lilly and Company
First posted: 2008-06-13
Enrollment: 22
Sex: FEMALE
Minimum age (years): 20
Maximum age (years): 48
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Idiopathic osteoporosis (IOP) is an uncommon disorder in which otherwise healthy young individuals sustain one or more low-trauma fractures. Teriparatide \[PTH(1-34)\], which is FDA approved for treatment of osteoporosis in men and postmenopausal women, works by stimulating bone formation. The investigators hypothesize that teriparatide will significantly increase bone density (BMD) and improve bone structure in premenopausal women with IOP.

Detailed description: Idiopathic osteoporosis (IOP) is an uncommon disorder in which otherwise healthy young individuals sustain one or more low-trauma fractures. In studies of IOP in men, histomorphometric indices of bone formation are depressed, and affected men respond to PTH(1-34) with robust increases in lumbar spine (LS) bone mineral density (BMD). This is the beginning of the third year of an R01 (AR4989603) investigating the etiology and pathogenesis, as well as the histomorphometric and bone microarchitectural features of IOP in premenopausal women. There is evidence of markedly decreased bone formation and microarchitectural deterioration with decreased mechanical competence/strength.

Teriparatide \[PTH(1-34)\] is an anabolic agent that stimulates bone formation and improves bone microarchitecture. Based on findings, the investigators hypothesize that teriparatide will significantly increase BMD and improve microarchitecture in premenopausal women with IOP.

This is an open-label study of carefully characterized premenopausal women with IOP who are participating in a NIH-funded study and who have fragility fractures or very low bone density. Participants in the study will receive 18-24 months of teriparatide and the effects on BMD and microstructure, bone mechanical competence, and bone turnover will be assessed. In order to assess whether teriparatide stimulates bone formation to the same extent in women with IOP as it does in normal women, the study will compare the short-term changes (2 and 4 weeks) in biochemical markers of bone formation in response to teriparatide between women with IOP and normal women who are participating in another NIH-funded study as controls.

Eligibility criteria: Inclusion Criteria:

* Premenopausal women of all races.
* Ages 20 to 48.
* Regular menses (at least 8 periods in the last 12 months).
* FSH \< 20 mIU/ml during the early follicular phase, to exclude women in the perimenopause.
* Fracture subjects: documented low trauma fracture(s) at age \>= 18 (e.g., fracture associated with a fall from a standing height or less).
* Low BMD subjects: DXA BMD T score less than or equal to 2.5 at the LS, total hip, femoral neck or distal radius, who have not had a fracture.
* Control subjects: DXA BMD T score greater than or equal to 1.0 at the LS, total hip, femoral neck and distal radius, who have not had a fracture.
* All subjects must use appropriate birth control methods to prevent pregnancy for the duration of teriparatide treatment.

Exclusion Criteria:

* Secondary Causes of Osteoporosis.
* Disorders of mineral metabolism: primary or secondary hyperparathyroidism (serum intact PTH \> 65 pg/ml), vitamin D deficiency (serum 25OHD \< 30 ng/ml), hypercalciuria (\>300 mg/g creatinine), Paget's disease, clinical osteomalacia, osteogenesis imperfecta (OI).
* Recent pregnancy or lactation (within past year).
* Prolonged amenorrhea (\> 6 months) during reproductive years (except during pregnancy or lactation).
* History of anorexia nervosa.
* Malignancy, except cured basal or squamous cell skin carcinoma.
* Endocrinopathy: hyperthyroidism (elevated serum thyroxine and/or suppressed TSH), untreated hypothyroidism, Cushing's syndrome, prolactin-secreting pituitary adenoma.
* Renal insufficiency (serum creatinine above upper limit of female normal range).
* Liver disease (AST, ALT, bilirubin, total alkaline phosphatase activity above upper normal limit).
* Intestinal disorders (celiac disease, pancreatic insufficiency, inflammatory bowel disease).
* History or current use of glucocorticoids, anticonvulsants, anticoagulants, diuretics, methotrexate.
* Current use of depot preparations of progesterone or GnRH agonists.
* Current use of drug therapies for osteoporosis (estrogen preparations other than contraceptives, raloxifene, bisphosphonates, calcitonin, PTH). Subjects who agree to discontinue use of these medications will be eligible to participate 6 months after discontinuing raloxifene or calcitonin, and 12 months after discontinuing bisphosphonates. Total exposure to bisphosphonates must be \< 1 year. Subjects who have taken PTH at any time in the past will not be eligible.
* Additional contraindications to teriparatide use: Unexplained elevated total or bone specific alkaline phosphatase or prior external beam or implant radiation therapy involving the skeleton.

Primary outcomes:
measure: Change in Lumbar Spine Bone Density by Dual Energy X-ray Absorptiometry (DXA)
timeFrame: Baseline, Month 18 or 24 reported
Secondary outcomes:
Other outcomes:
Locations:
city: Omaha
country: United States
facility: Creighton University
state: Nebraska
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
Study officials:
affiliation: Columbia University
name: Elizabeth Shane, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Columbia University
name: Adi Cohen, MD
role: STUDY_DIRECTOR
References: