Treatment of Osteopenia/Osteoporosis after Allogeneic Hematological Cell Transplantation with Zoledronic Acid.

Decreased bone mineral density (BMD) has been found to be a relatively common complication following haematopoietic cell transplantation (HCT). Only some studies exist about therapy with antiresorptive substances such as bisphosphonates. These studies analyse either short time therapy or only the use for female patients (pts). The aim of this study was to test the effect and tolerance of zoledronic acid in long time survival pts after HCT. Methods: 40 pts with osteoporosis (WHO T-score<=−2.5 SD) or osteopenia (T-score −1,0 to −2.5) were included in this prospective phase II study. The dose was 4 mg intravenously all 3 months for 2 years (yrs) in combination with calcium, vitamin D and hormone-replacement therapy. 36 patients were evaluated, who got at least 3 doses (24 male, 12 female; mean age 43,8 yrs). The diagnoses were AML (15pts), ALL (5pts), CML (11pts), NHL (3pts), MDS (2pts). 16 pts received peripheral stem cells, 16 bone marrow, 4 pts both (median 15,6 months since HCT). All pts were evaluated according biochemical routine parameters, deoxypyridinoline (Dpd) and calcium excretion in urine by longitudinal measurements. The BMD of lumbar spine L1–L4 (LS) and total femur hip (FH) was mostly determined by dual-energy X-ray absorptiometry (Lunar Prodigy). 26 pts had at least two measurements since base line beginning of the treatment. Results: We found a significant increase of BMD at LS and FH (Table 1). The increase was better in younger pts <45yrs than in older pts at FH: 8,9 vs 2,9 % at 1 yr and 12,0 vs 3,4% at 2 yrs (p=0,007 and p=0.02). Dpd decreased from 6,2 nmol/mmol creatinine to 3,6 after 1 yr (p=0.009) and 3,2 after 2 yrs (p=0.04). By subgroup evaluation no significant changes of BMD were observed by testing pts with (n=20) or without (n=6) corticosteroid therapy for GvHD before or during the study (n= 7 and n=19) and by testing pts with osteoporosis (n=13) vs osteopenia (n=13), sex differences, diagnoses or time to HCT. Zoledronic acid was well tolerated. 1 of the 40 pts was excluded after the fist dosis because of dramatically myalgia. 6 pts had mild flu-like syndromes, bone pain, chest pain or headache. Zoledronic acid increases BMD and reduces Dpd excretion significantly in patients with bone loss after allogeneic hematological cell transplantation.