A Randomized, Double Blinded Study of Risedronate Versus Placebo for the Prevention of Bone Loss in Patients Receiving High Dose Corticosteroids for the Treatment of Acute Lymphocytic Leukemia and Lymphoblastic Lymphoma

Corticosteroid therapy is a well-known cause of osteoporosis. Studies have shown that the use of bisphosphonates such as risedronate can prevent bone loss in patients receiving moderate to high doses of corticosteroids. Patients with acute lymphoblastic leukemia and lymphoblastic lymphoma (ALL/LL) are at high risk of bone loss due to both leukemia and high dose steroids used in chemotherapy regimens.

The primary objective was to determine whether the use of risedronate decreases the amount of bone loss in adult patients with ALL/LL receiving chemotherapy with high dose corticosteroids when compared to placebo.

Adult patients with newly diagnosed ALL/LL receiving Hyper-CVAD or BFM were randomly assigned to receive either risedronate 35 mg weekly or placebo. Both patients and physicians were blinded to the treatment assignment. Patients in both arms were given vitamin D and calcium. Bone mineral density (BMD) using DEXA scan was measured at baseline and at 6 months. Patients who lost more than 10% BMD when compared to baseline measurements were taken off the study and unblinded. We excluded patients with osteoporosis.

36 patients were randomized to each treatment arm. Median age was 29 years in the risedronate arm and 42 years in the placebo arm (p=0.06). 22 patients had an available 6 month DEXA scan in the risedronate arm and 29 in the placebo arm. Patients on the placebo arm had a greater decrease in BMD at the left hip (mean −0.12) and right hip (mean −0.11) when compared to baseline than patients in the risedronate arm (left hip mean −0.08; right hip mean −0.078) and this was statistically significant (p=0.03 and p=0.04, respectively). There were no significant differences observed in the lumbar spine between the two groups. 11/22 (50%) patients in the risedronate arm were taken off study for significant % decrease in BMD at any site, and 18/29 (62%) patients in the placebo arm (p=0.28). Two patients, 1 in each arm, experienced a vertebral fracture during the first 6 months of chemotherapy.

Adult ALL/LL patients receiving high dose corticosteroids with HyperCVAD have profound bone loss and should be monitored for this while receiving chemotherapy. Risedronate significantly reduced bone loss at the hips, but did not have a significant effect at the lumbar spine. Despite treatment with risedronate, 50% of patients had profound bone loss during the first 6 months of chemotherapy, thus a more potent bisphosphonate may be necessary to preserve bone mass, particularly at the lumbar spine. Whether a potent bisphosphonate or an agent such as a monoclonal antibody to RANK ligand will reduce fractures and improve quality of life should be studied in future clinical trials.

Hu:Amgen: Research Funding, Speakers Bureau. Cabanillas:Procter and Gamble: Research Funding.