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Byline: K. Kananen (1), L. Volin (2), K. Laitinen (3), T. Ruutu (2), M. J. Valimaki (1) Keywords: Osteoporosis; Osteoprotegerin; sRANKL; Stem cell transplantation Abstract: Purpose: Osteoporosis is a long-term complication of allogeneic stem cell transplantation (SCT). Receptor activator of nuclear factor-IoB ligand (RANKL) increases osteoclast activity, while osteoprotegerin (OPG) neutralizes RANKL. A deficiency of OPG or an excess of RANKL may contribute to post-SCT bone loss. Methods: Serum OPG and soluble RANKL (sRANKL) concentrations were determined in 30 patients who received calcium, vitamin D and sex steroids -- with or without pamidronate -- prior to SCT and 1, 3, 6, and 12 months post-SCT and compared to those in healthy controls. Results: Despite all treatments patients lost bone at the hip. At baseline, serum OPG was similar in patients and controls in the two patient groups it increased by 26--27% at 6 months post-SCT (p=0.002--0.028) and over the control level (p=0.002). Serum sRANKL concentrations were also similar in patients and controls at baseline. In those patients receiving pamidronate sRANKL concentrations decreased by 42% (p=0.0007) at 3 months post-SCT. The findings on the effect of SCT on OPG and sRANKL serum levels were ascertained in 28 additional patients who did not receive pamidronate, at a median of 122 days after SCT. In this latter group, OPG but not sRANKL concentrations were clearly elevated (p&lt 0.001) in comparison to healthy controls. In conclusion, the present study fails to support the view that an excess of sRANKL or a deficiency of OPG would have a substantial impact on bone loss in SCT-recipients. Conclusion: Serum sRANKL concentrations may be modulated by bisphosphonates. Author Affiliation: (1) Division of Endocrinology, Department of Medicine, Helsinki University Central Hospital, 00290, Helsinki, Finland (2) Division of Haematology, Department of Medicine, Helsinki University Central Hospital, Helsinki, Finland (3) Department of Obstetrics and Gynaecology, Helsinki University Central Hospital, Helsinki, Finland Article History: Registration Date: 11/11/2005 Received Date: 30/06/2005 Accepted Date: 09/11/2005 Online Date: 31/12/2005