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Enhancing Osteoporosis Therapy: Can We Open the Anabolic Window?

Information source: University of Wisconsin, Madison
ClinicalTrials.gov processed this data on August 20, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Osteoporosis

Intervention: Teriparatide (Drug); Raloxifene (Drug)

Phase: Phase 4

Status: Completed

Sponsored by: University of Wisconsin, Madison

Official(s) and/or principal investigator(s):
Neil Binkley, MD, Principal Investigator, Affiliation: University of Wisconsin, Madison


Current osteoporosis therapies produce a prompt increase in bone mass, followed by only modest or no further subsequent gains. This limitation, known as the "remodeling transient," reflects the "coupling" of bone resorption with formation such that interventions impacting either of these processes lead to compensatory changes of the other. For example, medications which increase bone formation promptly also stimulate bone resorption. Thus, given the need to dramatically increase bone mass in patients with osteoporosis, it is necessary to "uncouple" formation and resorption. The investigators believe this to be possible using currently existing FDA-approved therapeutic agents, by using a novel, sequential approach. This pilot project will obtain preliminary data essential to support future work. In this study, the investigators will begin to explore the use of sequential anabolic treatment with teriparatide followed by antiresorptive therapy with raloxifene. The investigators propose that such sequential treatment will allow opening of the "anabolic window," the brief period of time following initiation of teriparatide therapy in which bone formation exceeds resorption.

Clinical Details

Official title: Enhancing Osteoporosis Therapy: Can We Open the Anabolic Window?

Study design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome:

Serum Markers of Skeletal Turnover (Serum CTX)

Serum Markers of Skeletal Turnover (Serum P1NP)

Secondary outcome:

Average Bone Mineral Density of the Spine at Baseline, 3 Months and 6 Months

Average Bone Mineral Density of the Proximal Femur (Hip) at Baseline, 3 Months and 6 Months

Average Bone Mineral Density of the One-third Radius at Baseline, 3 Months and 6 Months


Minimum age: 60 Years. Maximum age: 89 Years. Gender(s): Female.


Inclusion Criteria:

- Generally healthy, community-dwelling ambulatory post-menopausal women.

- Able and willing to sign informed consent.

- Age 60 to 89.

- Have osteoporosis defined as follows:

- BMD T-score of the lumbar spine, femur neck, total proximal femur or .3 radius of

- 2. 5 to -4. 0; note: the lumbar spine must include two vertebrae that are evaluable by

DXA in the opinion of the investigator. OR

- BMD T-score of the lumbar spine, femur neck, total proximal femur or .3 radius of

- 1. 5 or lower and either an atraumatic (in the opinion of the investigator)

nonvertebral fracture; [note: nonvertebral fracture sites include the wrist, hip, pelvis, ribs, humerus, clavicle, femur, tibia and fibula] or a minimum of two mild or one moderate or severe atraumatic vertebral fractures (defined using the Genant visual semi-quantitative scale).

- Baseline serum 25(OH)D concentration > 20 ng/ml and < 60 ng/ml.

- Able and willing to receive daily subcutaneous injections using a Forteo® pen.

Exclusion Criteria:

- History of exposure to external beam or implant radiation therapy involving the


- Paget's disease or unexplained elevations of alkaline phosphatase.

- Any history of venous thrombosis including deep vein thrombosis, pulmonary embolism,

retinal vein thrombosis and superficial phlebitis.

- Documented atherosclerotic vascular disease, including but not limited to prior

myocardial infarction, angina, atrial fibrillation, stroke and TIA.

- Marked hypertriglyceridemia (>500 mg/dl).

- History of prior treatment with estrogen resulting in hypertriglyceridemia (> 500


- Serum calcium, alkaline phosphatase, PTH or TSH outside the normal reference range.

- History of nephrolithiasis or urolithiasis within 10 years prior to enrollment; those

with a history of nephro- or urolithiasis must have an appropriate radiology study (e. g., IVP or KUB) within six months documenting absence of stones.

- Baseline 24-hour urine calcium > 250 mg.

- Known risk factors for hypercalcemia, e. g., malignancy, tuberculosis, sarcoidosis.

- History of any form of cancer except adequately treated squamous cell or basal cell

skin carcinoma.

- Use of active vitamin D analogs or high dose vitamin D (≥50,000 IU weekly) in the

last year.

- Active or suspected diseases (within 1 year prior to enrollment) that affect bone

metabolism, e. g., renal osteodystrophy, hyperthyroidism, osteomalacia, hyperparathyroidism.

- Known allergy, hypersensitivity, contraindication or intolerance to teriparatide or


- History of vaginal bleeding within the past year.

- Renal failure or substantial hepatic impairment. Note "renal failure" is defined as a

calculated creatinine clearance (using the Cockroft-Gault formula) of ≤ 35 ml/minute.

- Severe disease, e. g., cardiac, hepatic, pulmonary, etc., which may limit ability to

complete this study. Specifically, significantly impaired hepatic function (ALT or GGT 3x the upper limit of normal.

- Known malabsorption syndromes, e. g., celiac disease, active inflammatory bowel

disease, gastric bypass, etc.

- Use of anion exchange resins (e. g., cholestyramine) in the past month.

- Current use of warfarin (coumadin).

- Current use of highly protein-bound drugs including diazepam, diazoxide and


- Current use of digoxin.

- Any prior use of bisphosphonates, denosumab, strontium, fluoride, teriparatide or

parathyroid hormone.

- Prior use of estrogen, raloxifene, calcitonin or testosterone will be allowed if

discontinued more than six months previously. Low dose intra-vaginal estrogens (0. 3 mg or less of conjugated equine estrogen or equivalent) may be continued throughout the study.

- Treatment with glucocorticoids in doses ≥ 5 mg prednisone daily for > 30 days in the

prior year.

- Treatment with other drugs known to affect bone metabolism, e. g., anticonvulsants

except benzodiazepines or gabapentin, within the prior year. Note: oral calcium supplementation, vitamin D supplementation or diuretic use that has been stable for six months are allowed).

- Treatment within the last 30 days with any drug that has not received regulatory


- Metal in spine precluding spine QCT.

- Any condition that may interfere with evaluation of at least two lumbar vertebrae

determined on VFA performed at time of screening. Examples include confluent aortic calcification, severe osteoarthritis, spinal fusion and lumbar spine fractures.

Locations and Contacts

University of Wisconsin Osteoporosis Clinical Center and Research Program, Madison, Wisconsin 53705, United States
Additional Information

Starting date: September 2010
Last updated: September 18, 2014

Page last updated: August 20, 2015

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