The Effect of Zoledronic Acid on the Prevention of Bone Loss in Lymphoma Patients Receiving First-line Therapy

Patients with lymphoma are at high risk of osteoporosis. The majority have osteopenia at baseline, and the risk increases when treated with alkylating agents or corticosteroids. We conducted a randomized phase III trial to evaluate the effect of zoledronic acid on bone mineral density (BMD) in patients with lymphoma undergoing chemotherapy.

Full Abstract

Introduction

Osteoporotic bone cannot easily be restored to normal levels of strength; thus, the prevention of bone loss is crucial. Pamidronate can reduce the risk of bone loss and vertebral fractures in patients with lymphoma receiving chemotherapy. Zoledronic acid, a bisphosphonate approximately 100-fold more potent than pamidronate, has not been evaluated in lymphoma patients to date. We conducted a prospective trial to determine whether zoledronic acid reduces the risk of developing osteoporosis in this patient population.

Patients and Methods

All patients with newly diagnosed lymphoma seen at our institution from 2005 to 2009 were evaluated for protocol eligibility. Exclusion criteria included bone fractures, bone mineral density (BMD) T-scores poorer than −2.0, creatinine clearance < 60 mL/min, dental problems, and recent steroid or bisphosphonate use. Patients on study were stratified according to sex and menopausal status. Accrued patients received randomized therapy of either: (1) oral calcium and vitamin D (Ca + D), or (2) Ca + D and 4 mg zoledronic acid intravenously (I.V.) at baseline and at 6 months.

Results

To date, 33 patients have completed the study and have evaluable data. Patient characteristics included 17 men; 4 pre-menopausal women; 12 post-menopausal women; and median age, 62 years (range, 33–80 years). Seventeen patients had mild osteopenia upon enrollment. Patients who received zoledronic acid had stable median T-scores at all locations during the 12-month observation, whereas the T-scores of the control group decreased at every location evaluated (location: L1-4, P = .004; L neck, P = .001; L hip, P = .118; R neck, P = .009; R hip, P = .04).

Conclusion

Treatment with zoledronic acid in patients with newly diagnosed lymphoma prevents the BMD loss commonly seen in this population. Bone mass loss is difficult to restore, thus necessitating effective prevention strategies; additional studies should be conducted to confirm these findings.