This 2-year study will test the effectiveness of combining parathyroid hormone (PTH) and alendronate for treating osteoporosis in postmenopausal women. Alendronate is a drug used to treat osteoporosis and primarily prevents bone loss, whereas PTH increases bone formation. We will treat the study participants either with PTH and alendronate, alendronate alone, or PTH alone. We will determine the effects of these treatments by looking for changes in bone mineral density in the hip and spine.

Condition	Treatment or Intervention	Phase
Osteoporosis	Drug: PTH  Drug: Alendronate	Phase II

The PaTH study is a 2-year, multicenter, double-blind, placebo-controlled trial to test the efficacy of combining hPTH (1-84) and alendronate for treating osteoporosis in postmenopausal women.

238 women were randomized between 55 and 85 years of age to receive either: (1) PTH for 1 year followed by alendronate for 1 year; (2) PTH and alendronate for 1 year followed by alendronate for 1 year; (3) alendronate for 2 years; or (4) PTH for 1 year followed by placebo for 1 year. The primary endpoints are changes in bone mineral density at several sites and changes in biochemical markers.

In addition, we will assess specific biochemical markers of bone turnover (e.g., osteocalcin, deoxypridinoline, N-telopeptide, bone-specific alkaline phosphatase and bone sialoprotein) to determine if they can predict the skeletal response to combination therapy. We will also determine whether PTH positively affects ultrasound measurements in the calcaneus.

Ages Eligible for Study:  55 Years   -   85 Years,  Genders Eligible for Study:  Female

Accepts Healthy Volunteers

Criteria

Inclusion Criteria:

• Aged between 55 and 85 years
• Postmenopausal (have not had any menses in the last 5 years)
• Have a bone mineral density scan (DXA) that can be evaluated at the spine AND at the hip with a T-score equal to or below -2.5 at the spine or the femoral neck or total hip OR T-score equal to or below -2.0 at the spine or the femoral neck or total hip and have at least one of the following risk factors for fracture: (a) age > 65 years; (b) history of postmenopausal fracture (nonvertebral or vertebral); or (c) maternal history of hip fracture
• Willing and able to self-administer daily injections

Exclusion Criteria:

• Have used estrogen (oral or patch) for more than 1 month in the last 6 months or more than 12 months in the last 2 years
• History of more than 12 months of bisphosphonate use ever, or any use (> 4 weeks) within the past 12 months
• History of rhPTH (recombinant human PTH) use
• Any major life-threatening illnesses
• Type 1 or uncontrolled type 2 diabetes mellitus (defined as hemoglobin A1C > 10.0), or currently using insulin
• Vitamin D level < 15 nanograms/ml
• History of kidney disease (creatinine > 2.0 mg/dl)
• Renal insufficiency (creatinine clearance < 40 mg/min)
• Any history of kidney stones
• Any history of hypercalciuria or currently have urine calcium/creatinine >300 mg
• History of hypercalcemia, sarcoidosis, or hyperparathyroidism
• History of active or treated tuberculosis or other granulomatous disorders
• History of breast cancer, melanoma, or hematologic malignancy that has required treatment within the last 10 years
• History of bone cancer or any other metabolic bone disease that has required treatment within the last 10 years
• History of any other nonskin cancer that has required treatment within the last 10 years
• History of symptomatic esophageal reflux, achalasia or esophageal stricture
• Currently taking > 7.5 mg systemic prednisone or equivalent per day
• Currently using > two puffs, four times/day of inhaled steroids
• Currently taking anticoagulants or anticonvulsants
• Have used Calcitonin within the past 3 months
• Have used Raloxifene in the last 6 months or for more than 12 months in the last 2 years
• Have used Tamoxifen in the last 6 months or for more than 12 months in the last 2 years
• Have used fluoride for at least a month within the past 5 years
• Currently taking > 1000 IU/day vitamin D or vitamin D analogues or metabolites
• Currently taking thyroid hormone replacement AND have a TSH < 0.1mIU/L

Maine
      Maine Center for Osteoporosis, Bangor,  Maine,  04401,  United States
Minnesota
      University of Minnesota, Minneapolis,  Minnesota,  55415,  United States
New York
      Columbia University, New York,  New York,  10032,  United States
Pennsylvania
      University of Pittsburgh Medical Center, Pittsburgh,  Pennsylvania,  15213,  United States

Study chairs or principal investigators

Dennis Black, PhD,  Principal Investigator,  University of California, San Francisco   

Study ID Numbers:  NIAMS-045; N01-AR-9-2245
Record last reviewed:  February 2004
Record first received:  March 24, 2000
ClinicalTrials.gov Identifier:  NCT00005005
Health Authority: United States: Food and Drug Administration
ClinicalTrials.gov processed this record on 2004-10-29