Forteo for the Treatment of Unexplained Osteoporosis in Premenopausal Women

Condition(s) targeted: Menopause; Fracture; Osteoporosis

Intervention: Teriparatide (PTH 1-34) (Drug)

Phase: Phase 2/Phase 3

Status: Active, not recruiting

Sponsored by: Columbia University

Official(s) and/or principal investigator(s):
Elizabeth Shane, MD, Principal Investigator, Affiliation: Columbia University
Adi Cohen, MD, Study Director, Affiliation: Columbia University

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. We hypothesize that teriparatide will significantly increase bone density (BMD) and improve bone structure in premenopausal women with IOP.

Official title: Teriparatide for the Treatment of Idiopathic Osteoporosis in Premenopausal Women

Study design: Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome: Change in lumbar spine bone density by Dual energy x-ray absorptiometry (DXA) from baseline to 18 months.

Secondary outcome:

Change in serum biochemical indices of bone turnover and bone biopsy derived measures of resorption and formation versus baseline.

Change in urine biochemical indices of bone turnover and bone biopsy derived measures of resorption and formation versus baseline.

Prevalence of IOP subjects with serum indices of bone resorption and formation

Prevalence of healthy controls with serum indices of bone resorption and formation

Detailed description: Idiopathic osteoporosis (IOP) is an uncommon disorder in which otherwise healthy young individuals sustain one or more low-trauma fractures. In our 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). We are now beginning 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. We have found 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 upon our findings, we hypothesize that teriparatide will significantly increase BMD and improve microarchitecture in premenopausal women with IOP. We will test this hypothesis in an open-label study of carefully characterized premenopausal women with IOP who are participating in our 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, we 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 our NIH-funded study as controls.

Minimum age: 20 Years. Maximum age: 45 Years. Gender(s): Female.

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.

Creighton University, Omaha, Nebraska 68131, United States

Columbia University Medical Center, New York, New York 10032, United States

Starting date: August 2008
Last updated: April 6, 2015