Forteo Trial on Idiopathic Osteoporosis in Premenopausal Women

Inclusion Criteria:

• Premenopausal women, aged 20-45, with regular menses and no historical or biochemical secondary cause of osteoporosis; the lower age limit is to ensure epiphyses are fused, the upper to make it less likely that women will enter menopause during the study. All subjects under age 25 will be screened prior to drug administration to rule out open epiphyseal plates.
• Documented adult fractures judged to be low-trauma (trauma equivalent to a fall from a standing height or less) and/or T < -2.5 or Z score <-2.0 at the LS, FN or TH. Inclusion criteria vary slightly based on age category:
• Premenopausal women ages 20-35 years must have at least one major osteoporotic fracture (excluding fractures of fingers, toes and face) AND low BMD defined as a T-score or Z-score greater than or equal to -1.5.
• Premenopausal women above the age of 35 years should have a history of fracture AND/OR low BMD defined as Z-score < -2.0. Women above age 35 may also be enrolled on the basis on low BMD alone, without presence of prior low trauma fracture.
• Must be willing to use effective contraception throughout the period of study drug administration

Exclusion Criteria:

• History of any condition that increases the risk of osteosarcoma (Paget's disease, skeletal irradiation)
• Early follicular phase serum FSH>20 mIU/ml (to exclude perimenopausal women)
• Disorders of mineral metabolism: 1o/2 o hyperparathyroidism, osteomalacia, osteogenesis imperfecta (OI) or Ehlers Danlos (ED). Subjects will not routinely undergo genetic testing for OI or ED as part of their screening evaluation. However, each subject will have a detailed medical and family history and a complete physical examination by one of the physician investigators. Women with historical features or physical examination findings suggestive of OI or ED will be referred for genetic evaluation. If the genetic evaluation is positive for OI or ED, the subject will be excluded from participation.
• Vitamin D deficiency (serum 25-OHD<20 ng/ml). Women with levels of 20-30 ng/ml will be eligible after treatment with vitamin D has resulted in levels >30 ng/ml.
• Pregnancy or lactation within past 12 months
• Prolonged amenorrhea (> 6 months) during reproductive years (except pregnancy or lactation)
• History of an eating disorder (anorexia nervosa, bulimia)
• Malignancy, except cured basal or squamous cell skin carcinoma
• Endocrinopathy: new onset untreated hyperthyroidism, hypothyroidism, Cushing's syndrome, prolactinoma
• 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/current GCs, anticonvulsants, anticoagulants, methotrexate, depot progesterone, GnRH agonists
• Drugs for osteoporosis (raloxifene, bisphosphonates, denosumab, calcitonin, TPTD). Subjects who discontinue these medications will be eligible 3 months after stopping raloxifene or calcitonin, 12 months after stopping alendronate, risedronate, ibandronate, or pamidronate and 18 months after stopping denosumab or zoledronate. Total bisphosphonate exposure must be < 1 year. Subjects who have taken TPTD or zoledronate in the past will not be eligible.