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This version published online on November 16, 2004
Journal of Clinical Endocrinology & Metabolism, doi:10.1210/jc.2004-0509
A more recent version of this article appeared on February 1, 2005
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Submitted on March 16, 2004
Accepted on October 28, 2004

Short-term zoledronic acid treatment increases bone mineral density and marrow clonogenic fibroblast progenitors after allogeneic stem cell transplantation

Libuse Tauchmanovà, Patrizia Ricci, Bianca Serio, Gaetano Lombardi, Annamaria Colao, Bruno Rotoli, and Carmine Selleri*

Department of Molecular and Clinical Endocrinology and Oncology (L Tauchmanovà, MD PhD, A Colao MD PhD, G Lombardi MD, PhD), Division of Hematology (P Ricci BSc, B Serio MD, B Rotoli MD, C Selleri MD), Federico II University of Naples, 80131, Naples, Italy

* To whom correspondence should be addressed.
Carmine Selleri, E-mail: selleri{at}unina.it

Although osteoporosis is a relatively common complication after allogeneic stem cell transplantation (allo-SCT), the role of bisphosponates in its management has not yet been completely established. Thirty-two patients who underwent allo-SCT 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, fifteen of the patients with osteoporosis (n = 7) or rapidly progressing osteopenia (bone loss >5%/year), received three monthly doses of 4 mg of zoledronic acid intravenously. Fifteen patients were followed-up without treatment and all 30 patients were re-evaluated 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 1-year 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, while 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 in the 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.




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