Short-Term Zoledronic Acid Treatment Increases Bone Mineral Density and Marrow Clonogenic Fibroblast Progenitors after Allogeneic Stem Cell Transplantation

Abstract

Although osteoporosis is a relatively common complication after allogeneic stem cell transplantation, the role of bisphosphonates in its management has not yet been completely established. Thirty-two patients who underwent allogeneic stem cell transplantation were prospectively evaluated for bone mineral density (BMD) at the lumbar spine (LS) and femoral neck (FN) after a median period of 12.2 months. Then, 15 of the patients with osteoporosis or rapidly progressing osteopenia (bone loss > 5%/yr) received three monthly doses of 4 mg zoledronic acid iv. Fifteen patients were followed up without treatment, and all 30 patients were reevaluated after 12 months for BMD and bone turnover markers. By using enriched mesenchymal stem cells in the colony-forming units fibroblast (CFU-F) assay, we evaluated the osteogenic stromal lineage. This procedure was performed in both groups of patients at study entry and after 12 months. The average BMD loss was 3.42% at LS and 3.8% at FN during a 1-yr longitudinal evaluation in 32 patients. Subsequently, BMD increased at both LS and FN (9.8 and 6.4%, respectively) in the zoledronic acid-treated cohort. Hydroxyproline excretion decreased, and serum bone-specific alkaline phosphatase increased significantly, whereas serum osteocalcin increase did not reach the limit of significance. A significant increase in CFU-F growth in vitro was induced by in vivo zoledronic acid administration. In the untreated group, no significant change was observed in bone turnover markers, LS BMD (–2.1%), FN BMD (–2.3%), and CFU-F colony number. In conclusion, short-term zoledronic acid treatment consistently improved both LS and FN BMD in transplanted patients who were at high risk for fast and/or persistent bone loss, partly by increasing the osteogenic progenitors in the stromal cell compartment.