Pamidronate, Vitamin D, and Calcium for the Bone Disease of Kidney and Heart Transplantation

Bone is lost rapidly and fractures occur in 10-20% of patients who receive organ transplants within 2 years. The purpose of this study is to evaluate long-term effects of a pamidronate-vitamin D-calcium regimen on bone loss, fractures, and safety in recipients of kidney and heart transplants.

Study Overview

• Status: Completed
• Conditions: Transplant Bone Disease
• Intervention / Treatment: Drug: Pamidronate; Drug: vitamin D; Drug: Calcium Carbonate

Detailed Description

Pamidronate improves bone mass in numerous disorders of bone. Other bisphosphonates, as well as pamidronate, have been proven to be beneficial in steroid-related bone disorders. Steroid treatment is a major cause of bone loss after organ transplantation. Small, short-term studies suggest that pamidronate prevents bone loss in kidney and heart transplant recipients.

Many bisphosphonates cannot be used in patients with decreased kidney function. However, pamidronate can be given to these patients. This is an advantage of pamidronate in kidney and heart transplantation because of the frequent occurrence of decreased kidney function in these groups. Another advantage of pamidronate is that it is administered intravenously. Oral bisphosphonates commonly produce esophagitis, which is a challenging problem in the transplant population. Potential side-effects of pamidronate include transient hypocalcemia, lymphopenia, low-grade fever, myalgias and nausea. Recently, rare cases of proteinuria and kidney failure were reported in cancer patients receiving high-dose pamidronate. Although this side effect has not been reported in other types of patients receiving pamidronate, this is a safety concern that warrants further scrutiny in the transplant population.

In addition to bisphosphonate treatment, supplementation with calcium and vitamin D may preserve bone after organ transplantation. Prior studies have compared bisphosphonates to calcium and vitamin D regimens. However, a combination regimen including each of these treatments may preserve bone mass better than a single treatment. Data regarding treatment with a combination of a bisphosphonate, calcium, and vitamin D are lacking in kidney and heart transplantation.

Comparison(s): In a prospective, open-label, single arm trial, Pamidronate (60-90 mg) is administered within 2 weeks after kidney or heart transplant and every 6 months for 2 years. Participants are prescribed vitamin D 800 units/d or calcitriol 0.25 microgram/d if serum creatinine is greater than 2 mg/dl, and calcium carbonate 1500 mg/d.

The primary outcome is bone mineral density measured by dual-energy X-ray absorptiometry at baseline and after years 1 and 2. Fracture events and serum calcium, parathyroid hormone, creatinine, and dipstick proteinuria are also measured.

• Study Type: Interventional
• Enrollment (Actual): 43
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Washington
    • Spokane, Washington, United States, 99204
      • Providence Medical Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Kidney or heart transplant recipients

Exclusion Criteria:

• Hyperparathyroidism

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Pamidronate, Vitamin D, and Calcium; 60mg or 90mg given at baseline, 6,12,18, and 24 months vitamin D 800 units/day calcium carbonate 1500 milligrams/day	Drug: Pamidronate; 60mg or 90mg given at baseline, 6,12,18, and 24 months; Other Names: Transplant Bone Disease; Drug: vitamin D; baseline, 6,12 months; Other Names: Vitamin D administration in Transplant; Drug: Calcium Carbonate; baseline, 6,12 months; Other Names: Calcium administration in Transplant

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Bone mineral density measured by dual-energy X-ray absorptiometry	Performed at 1 year and 2 years.	Every 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Fracture events	Evaluated at 6, 12, 18 months and 2 years	Every 6 months
serum calcium	baseline, 6,12,18 months and 2 years	Every 6 months
parathyroid hormone	baseline, 6,12,18 months and 2 years	Every 6 months
serum creatinine and estimated glomerular filtration rate	Performed at 6,12,18 months and 2 years	Every 6 months
proteinuria	Evaluated at 6,12,18 months and 2 years	Every 6 months

Collaborators and Investigators

• Sponsor: Providence Health & Services
• Collaborators: University of Washington; Ochsner Health System; The Heart Institute of Spokane
• Investigators: Principal Investigator: Katherine R. Tuttle, MD,FASN,FACP, Providence Medical Research Center

Study record dates

Study Major Dates

• Study Start: January 1, 1999
• Primary Completion (Actual): November 1, 2002
• Study Completion (Actual): November 1, 2002

Study Registration Dates

• First Submitted: March 10, 2006
• First Submitted That Met QC Criteria: March 10, 2006
• First Posted (Estimate): March 14, 2006

Study Record Updates

• Last Update Posted (Actual): August 29, 2018
• Last Update Submitted That Met QC Criteria: August 27, 2018
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Keywords: fractures; vitamin D; bisphosphonates; calcium supplement; corticosteroid therapy
• Additional Relevant MeSH Terms: Musculoskeletal Diseases; Bone Diseases; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Gastrointestinal Agents; Micronutrients; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Antacids; Vitamin D; Cholecalciferol; Calcium; Vitamins; Calcium, Dietary; Ergocalciferols; Calcium Carbonate; Pamidronate
• Other Study ID Numbers: HI497