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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Transplant Bone Disease

Intervention / Treatment
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* Drug: Pamidronate
* Drug: vitamin D
* Drug: Calcium Carbonate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Kidney or heart transplant recipients Exclusion Criteria: Hyperparathyroidism

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

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

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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bisphosphonates, vitamin D, calcium supplement, corticosteroid therapy, fractures