To Learn How Bone Structure and Bone Mass Change After Long-term PPI Use (BE-CAST)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01306799
Recruitment Status : Completed
First Posted : March 2, 2011
Last Update Posted : March 30, 2017
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
National Institutes of Health (NIH)
Information provided by (Responsible Party):
University of Pennsylvania

Brief Summary:
Patients with severe acid reflux and/or Barrett's esophagus are recommended to take Proton pump inhibitors (PPIs)indefinitely to prevent complications such as strictures or the development of a type of esophageal cancer. Recently, some studies suggested that taking these medications on a long-term basis may affect the bone. Therefore, it is important to learn whether these medications may lead to accelerated bone loss so that effective preventive measures can be developed for patients who require these medications for acid-related conditions. Several studies reported that patients receiving PPIs for many years may have increased risk of hip fractures. However, it is unclear whether this is because the PPIs cause reduced bone density or whether the increased risk of fractures has nothing to do with PPIs and is because patients who require PPIs have other illnesses that cause the increased fractures. The purpose of the study is to learn how bone structure and bone mass change after long-term PPI use.

Condition or disease
Barrett's Esophagus Erosive Esophagitis Gastroesophageal Reflux Disease(GERD)

Detailed Description:
Proton pump inhibitors (PPIs) are among the most widely used medications. It is becoming increasingly common for patients to take these potent acid suppressants on a long-term and continuous basis for erosive esophagitis, Barrett's esophagus and protection against nonsteroidal anti-inflammatory drug-related gastropathy. PPI therapy leads to elevated serum gastrin levels and may impair the absorption of calcium and food-bound vitamin B12. PPI-induced hypergastrinemia has a direct trophic effect on the parathyroid glands, leading to parathyroid hyperplasia, increased parathyroid hormone secretion and bone loss. Furthermore, both calcium malabsorption and vitamin B12 deficiency are associated with reduced bone mineral density (BMD) and increased osteoporotic fracture risk. Consistent with these data, recent studies revealed a positive association between PPI therapy and the risk of osteoporotic fractures. Peripheral quantitative computed tomography (pQCT) can provide a three-dimensional structural analysis of trabecular and cortical volumetric BMD (vBMD) and dimensions. These data are imperative for a valid assessment of the effect of chronic PPI therapy on bone strength. The investigators hypothesize that PPI therapy leads to decreased cortical and trabecular vBMD, cortical dimensions and bone strength.

Study Type : Observational
Actual Enrollment : 106 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Effect of Chronic Proton Pump Inhibitor Therapy on Bone Mineral Density and Bone Structure in Mid to Late Adulthood
Study Start Date : January 2010
Actual Primary Completion Date : April 2015
Actual Study Completion Date : April 2015

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Barrett's Esophagus, Erosive Esophagitis, GERD

Primary Outcome Measures :
  1. Volumetric bone mineral density as measured by pQCT [ Time Frame: 3 years ]

Secondary Outcome Measures :
  1. measure PTH levels at each study visit [ Time Frame: 3 years ]
    monitor change in PTH levels because long-term PPI therapy may have an affect on parathyroid glands, increasing parathyroid hormone (PTH) secretion.

  2. measure vitamin B12 levels at each study visit [ Time Frame: 3 years ]
    low B12 levels have been associated with reduced bone mineral density (BMD) as well osteoporotic fracture risk

Information from the National Library of Medicine

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Ages Eligible for Study:   40 Years to 75 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population
  • Patients who either are starting or have been receiving long-term continuous PPI therapy for erosive esophagitis or Barrett's esophagus diagnosed within the past three years.
  • Patients who are starting PPI therapy for gastroesophageal reflux disease (GERD) and have shown a subjective improvement in symptoms within 4 weeks of starting therapy. This improvement will be assessed either through documentation in their medical record or through telephone interview with permission from their physician.
  • Patients who are starting PPI therapy for ulcer prophylaxis in a setting of chronic aspirin use.
  • Patients who are starting PPI therapy for extraesophageal manifestations of GERD.

Inclusion Criteria:

  • women between 50 to 75 years old
  • men between 40 to 75 years old
  • Barrett's esophagus and Erosive esophagitis diagnosed within the past three years, GERD or Acid Reflux, taking chronic aspirin
  • Starting long-term PPI therapy or currently on long-term PPI therapy

Exclusion Criteria:

  • Pre-menopausal women
  • men under 40 years old

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01306799

United States, Pennsylvania
University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104
Sponsors and Collaborators
University of Pennsylvania
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
National Institutes of Health (NIH)
Principal Investigator: Yu-Xiao Yang, MD, MSCE University of Pennsylvania

Responsible Party: University of Pennsylvania Identifier: NCT01306799     History of Changes
Other Study ID Numbers: 810599
1R01AR057102-01 ( U.S. NIH Grant/Contract )
First Posted: March 2, 2011    Key Record Dates
Last Update Posted: March 30, 2017
Last Verified: March 2017

Keywords provided by University of Pennsylvania:
Barrett's Esophagus
Erosive Esophagitis
Proton Pump Inhibitor (PPI)
Bone Density
ulcer prophylaxis

Additional relevant MeSH terms:
Gastroesophageal Reflux
Barrett Esophagus
Esophageal Motility Disorders
Deglutition Disorders
Esophageal Diseases
Gastrointestinal Diseases
Digestive System Diseases
Digestive System Abnormalities
Proton Pump Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action