Zoledronic Acid Versus Alendronate for Prevention of Bone Loss After Organ Transplantation

Patients who have undergone heart or liver transplantation are usually required to remain on
medications, such as Prednisone and Cyclosporine A or Tacrolimus, that prevent the body from
rejecting the transplanted organ. These medications may cause bone loss which leads to
thinning of the bones (osteoporosis) and therefore greatly increase the risk of having broken
bones (fractures) after transplantation. Several published studies have shown that 14% to 35%
of heart transplant patients develop fractures (spine, ribs and hip) during the first year
after transplantation. We have previously shown that alendronate (Fosamax), a drug approved
by the FDA for prevention and treatment of postmenopausal osteoporosis and prednisone-induced
osteoporosis, prevents bone loss after heart transplantation. We are conducting this study to
determine whether a newer drug, zoledronic acid, is as effective as alendronate.

This study is a randomized, double-blind, placebo-controlled 2-year study. Participants will
receive one dose of active zoledronic acid during the first month after heart or liver
transplantation and weekly placebo alendronate pills or one dose of placebo zoledronic acid
and weekly active alendronate pills for the first year after transplant. Over 2 years,
participants will provide blood samples on nine occasions. Bone density will be performed 4-5
times and spine xrays will be performed twice.

Inclusion Criteria:

- A man or woman, aged 20 to 70, of any race who has had a heart or liver transplant

Exclusion Criteria:

- hyperparathyroidism

- Paget's disease

- hyperthyroidism

- cancer

- severe kidney disease,

- intestinal disease

- active peptic ulcer disease

- current or past treatment for osteoporosis

- pregnancy or lactation

- severe oral/dental disease