The purpose of this study is to evaluate the adequacy of zoledronic acid in maintaining bone
mass after two years of treatment with Forteo, in postmenopausal women.
A screening period of 3 to 6 weeks will precede the treatment period. At the baseline visit,
patients whose eligibility is confirmed will be treated with ZA and followed for 12 months.
Safety and efficacy will be assessed at regular intervals (day one, day 10, month 2, month 6,
month 9 and month 12). Renal safety will be assessed prior to the i. v. dose of study
medication, day 10 after the i. v. dose of study medication and at 12 months. Bone density at
the lumbar spine (L1-4) and total hip will be performed at 6 months and at the end of the 12
month treatment period. Biomarker analyses for secondary endpoint will be performed for at
day 10, month 2, month 6, month 9 and month 12.
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
