Intervenous (IV) Zoledronic Acid After Forteo in Postmenopausal Women

Inclusion Criteria:

• Postmenopausal women to age 85, inclusive
• Finish treatment of 12 months or longer with Forteo
• Signed informed consent prior to initiation of any study-mandated procedure.

Exclusion Criteria:

• Hip and spine DXA T-score >-1.0
• Patients with 25-(OH) vitamin D levels less than 15 ng/mL at Visit 1. (Patient can be repleted with vitamin D 50,000 units biweekly for up to 2 months and re-screened anytime during the 2 months while continuing Forteo.)
• Baseline renal insufficiency (calculated creatinine clearance less than 40.0 mL/min (MDRD) at Visit 1 and/or Visit 2 or urine dipstick greater than or equal to 2+ protein without evidence of contamination or bacteriuria (may be repeated one time at least a week apart if there is suspicion of contamination). Patients with calculated creatinine clearance equal to or greater than 40.0 mL/min and less than 60.0 mL/min or serum creatinine greater than the upper limit of normal at Visit 1 must be retested between Visit 1 and 2. Patients with calculated creatinine clearance greater than 60.0 mL/min and serum creatinine within normal limits at Visit 1 do not require re-test.
• Patients who require re-test of creatinine clearance between Visit 1 and 2 will be excluded if there is an increase in serum creatinine greater than 0.5 mg/dL between Visit 1 and Visit 2.
• Serum calcium <8.5 or >11.0 mg/dl at Visit 1
• AST or ALT greater than twice the upper limit of normal
• Serum alkaline phosphatase greater than 1.5 times the upper limit of normal (liver fraction)
• No history of retinopathy or nephropathy especially in the presence of uncontrollable IDDM with Hb1 AC > 10%
• Hypersensitivity to bisphosphonates
• Treatment with biphosphonates while on Forteo
• Prior treatment with i.v. biphosphonates
• Estrogen, calcitonin, raloxifene use prior to Forteo treatment are not exclusions, but concomitant therapy during with any bone agents during the trial will not be permitted
• Any prior use of strontium ranelate or sodium fluoride
• Chronic use of systemic corticosteroids (oral or i.v.) within the last year:

NOTE: Use of corticosteroids in forms such as topical creams, nasal or inhaled formulations or those injected locally (intra-articularly) are NOT exclusionary.

• Prior exposure to anabolic steroids or growth hormone within 6 months prior to randomization
• Treatment with any investigational drug(s) and/or devices within 30 days prior to randomization.
• History of iritis or uveitis, except when secondary to trauma, and must have resolved for more than 2 years prior to randomization.

• Cancer exclusions:

  • Patients with a new diagnosis or active treatment for any malignancy less than or equal to 12 months prior to Visit 1.
  • Patients with evidence of any metastases on or prior to randomization, or with a history of metastases
  • Subjects with evidence of paraneoplastic syndrome, especially those characterized by hypercalcemia during screening or by history
  • Patients with the following may be included: basal cell or squamous cell carcinoma of the skin, colonic polyps with non-invasive malignancy which have been removed, and Carcinoma in-situ (CIS) of the prostate (Stage I only) that has been surgically removed.
• Previous major solid organ or bone marrow transplant recipient or on a transplant waiting list
• Any disease of the spine that would preclude the proper acquisition of a lumbar spine DXA (L1-L4) e.g., implantable devices, scoliosis, ankylosing spondylitis, DJD. (Less than two lumbar spine vertebral bodies evaluable)
• Active primary hyperparathyroidism or hypoparathyroidism
• Subject with complete thyroidectomy
• Active hyperthyroidism
• Hypothyroidism not treated with adequate replacement therapy
• History of multiple myeloma or Paget's disease
• Patients with severe dental problems or current dental infections, or with recent or impending dental surgery within three months of dosing
• Any medical or psychiatric condition which, in the opinion of the investigator, would preclude the participant from adhering to the protocol or completing the trial per protocol