Primary Objective:

• Evaluate the effect of zoledronate on change in bone mineral density (BMD) at the total lumbar spine and femoral neck.

Secondary Objectives:

• Evaluate the effect of zoledronate on change in BMD at the total hip
• Evaluate risk factors for developing osteoporosis on chemotherapy
• Determine correlative markers for response to zoledronate 4. Evaluate zoledronate effect on new bone fractures 5. Evaluate the cost-effectiveness of zoledronic acid (with calcium and vitamin D) versus standard treatment (calcium and vitamin D alone).

Medicines called "bisphosphonates" have been shown to help people with cancer that has spread to their bones. Zoledronic acid is a "bisphosphonate". Some bisphosphonates are pills that can be swallowed. Other bisphosphonates such as zoledronic acid need to be given by vein (or intravenously). Some studies have shown that people with multiple myeloma, breast cancer, and prostate cancer that had spread to the bone had less side effects from their bone disease when they were treated with bisphosphonates by vein.

If you are found to be eligible to take part in this study, you will be randomly assigned (as in the toss of a coin) to one of two treatment groups. Participants in one group will receive standard care with calcium and Vitamin D alone. Participants in the other group will receive standard care with calcium and Vitamin D plus zoledronic acid. There is an equal chance of being assigned to either group. Both you and your study doctor will know if you are being treated with zoledronic acid.

You will be asked to come to the doctor's clinic 5 times over about 12 months (at the start of the study [baseline] and then every 3 months). Each visit should take about 1 hour. Participants in the zoledronic acid group will receive an infusion of zoledronic acid by vein at baseline and at 6 months into the study. The infusion will last about 30 minutes. This infusion procedure may or may not be done at the same time as your already scheduled chemotherapy treatment.

You will take calcium and Vitamin D pills while on study at amounts recommended for prevention of osteoporosis.

You will have a physical exam done at every visit. Various x-rays and/or bone density scans will be repeated after 12 months. Your doctor may also want to do additional bone density or x-ray scans if you have new symptoms or your symptoms get worse.

Before each treatment, you will have a blood test (about 1-2 teaspoons of blood) to make sure your kidneys are okay before each treatment with zoledronic acid. At each visit. your doctor or nurse will ask you how you are feeling and will ask about any medications you are taking or any medical problems you have had since your last visit. You will be asked to complete questionnaires about how you are feeling at certain visits. These questionnaires are 1 page long and should only take a few minutes to complete.

It is anticipated that your participation in this study will be 12 months. If your cancer gets worse, or if your doctor feels that you should be treated with a different medicine, you will be taken off of this study and your doctor will talk to you about other medicines that may be better for you.

Participants who received Zoledronic Acid will be contacted regularly to ask about any experience of osteonecrosis (bone death), for 10 years from the time they enroll on study. They will be interviewed by telephone call every 6 months.

This is an investigational study. Zoledronic acid is approved by the FDA for the treatment of high calcium levels in the blood. Zoledronic acid has not been approved by the FDA for what it is being used for in this study. After the treatment ends, you may continue to receive zoledronic acid or a similar drug, if your cancer doctor feels that it would help you. About 72 patients will take part in this study. All will be enrolled at M. D. Anderson.

Inclusion Criteria:

1. Diagnosis of Non-Hodgkin's Lymphoma (B- or T-cell) or Hodgkin's lymphoma.
2. Prior Chemotherapy</= 4 weeks of treatment.
3. Age >/= 18 years old.
4. Eastern Cooperative Oncology Group (ECOG) Performance Status 0-3.
5. Estimated creatinine clearance >/= 60 ml/min.
6. Must sign an informed consent form.

Exclusion Criteria:

1. Radiologic evidence of vertebral or hip fracture.
2. BMD T-score less than (i.e., worse than or more negative than) -2.0 at any of the following sites: lumbar spine, femoral neck, or total hip.
3. Patients with secondary non-lymphomatous cancers metastatic to bone. However, other secondary cancers are allowed.
4. Spinal cord compression due to vertebral collapse.
5. Bisphosphonate treatment in the prior 6 months or steroid use (greater than 35 mg of prednisone equivalent steroids) in the prior 3 months. The use of topical, inhaled, or nasal steroids is allowed.
6. Primary hyperparathyroidism.
7. Active osteomalacia.
8. Untreated hypocalcemia (ionized, iCa), Ionized Ca level must be within normal limits prior to enrollment.
9. Untreated secondary hyperparathyroidism, Patients with abnormal parathyroid hormone (PTH) levels may be enrolled as long as they are being treated.
10. Untreated vitamin D deficiency, Vitamin D level may be abnormal and patient may be enrolled as long as they are being treated.
11. Untreated low testosterone (test in men only), testosterone level may be abnormal and patient may be enrolled as long as they are being treated.
12. Paget's disease.
13. Pregnant or breast-feeding.
14. Radiotherapy involving the mandible.
15. Current active dental problems including infection of the teeth or jawbone (maxilla or mandibular); dental or fixture trauma, or a current or prior diagnosis of osteonecrosis of the jaw (ONJ), or of exposed bone in the mouth, or of slow healing after dental procedures.
16. Recent (within 3 weeks) or planned dental or jaw surgery (e.g.. extraction, implants).
17. Patients with abnormal renal function as evidenced by either a serum creatinine greater than 3 mg/dL or by a calculated creatinine clearance of < 60 mL/minute.
18. Known hypersensitivity to zoledronic acid or other bisphosphonates.
19. Hypercalcemia: corrected Ca > 10.2 mg/dL or ionized Ca > 1.32 mmol/L

4 years, 3 months