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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

Byline: M. J. Valimaki (1), K. Laitinen (2), K. Laitinen (3), A. Patronen (3), H. Puolijoki (3), H. Puolijoki (4), J. Seppanen (3), L. Pylkkanenand the Probone Study Group* (3) Keywords: Key words:Bisphosphonates -- Bone markers -- Bone mineral density -- Clodronate -- Osteoporosis Abstract: This double-masked, placebo-controlled study was undertaken to determine the efficacy and safety of oral clodronate in the prevention of bone loss in early postmenopausal women with vertebral osteopenia. Altogether 610 women with a mean age of 53 years were recruited for the study. They were 1--5 years postmenopausal and their lumbar spine bone mineral density (BMD) was at least 1 standard deviation below the mean of premenopausal women (T-score a$?-1). The subjects were randomized into five study groups to receive either placebo, clodronate 65 mg, 400 mg or 800 mg daily, or intermittent clodronate in 3 month cycles with 400 mg daily for 15 days followed with no treatment for 75 days for 3 years. One hundred and eighty-seven of 509 women who completed the primary study continued in the extension study of 2 years in which previous placebo users were switched to clodronate 800 mg daily, while previous users of 400 mg or 800 mg of clodronate used either placebo or 800 mg of clodronate daily. In the primary study clodronate was administered in the evening, and in the extension 1 h before breakfast on an empty stomach. In the primary study mean changes in lumbar spine BMD were -3.4% in the placebo group and +0.4% in 800 mg clodronate group [difference between groups at 3 years 3.8% (95% CI 2.7% to 4.9%, p&lt 0.0001)], and in the trochanter area BMD -1.1% in the placebo group, and + 0.4% in the 800 mg clodronate group [difference between groups at 3 years 1.5% (95% CI 0.05% to 2.9%)]. During the extension study mean changes in lumbar spine BMD were +1.5% in the clodronate group and -0.2 % in the placebo group [difference between groups 1.7% (CI 0.4% to 3.0%, p = 0.010)] and in trochanter BMD were +2.5% in the clodronate group and no change in the placebo group [difference between groups 2.1% (CI 0.3% to 3.9%, p = 0.007)]. No statistically significant differences between the placebo and 800 mg clodronate groups were found in the femoral neck BMD. In the primary study the urinary excretion of type I collagen aminoterminal telopeptide (NTX) decreased by 44% (p&lt 0.0001 compared with placebo) and that of deoxypyridinoline by 18% (p&lt 0.0001) in the clodronate 800 mg group. In the extension study urinary NTX decreased by 51% (p&lt 0.0001) in those who were switched to 800 mg of clodronate and increased by 67% (p&lt 0.0001) in those who stopped using that dose. There was no difference in the frequency of gastrointestinal complaints between clodronate- and placebo-treated patients in the primary study, but they were more common among women who received clodronate in the extension phase. Clodronate in daily doses of 400--800 mg caused a slight elevation of aminotransferase levels, usually within the reference range. In bone biopsies no defect in mineralization was found. In conclusion, clodronate in a daily dose of 800 mg prevents early postmenopausal bone loss at the sites of the skeleton in which cancellous bone predominates. It effectively reduces bone resorption and bone turnover rate. Antifracture efficacy of clodronate remains to be established by prospective, placebo-controlled trials. Author Affiliation: (1) Division of Endocrinology and (2) Department of Internal Medicine, Helsinki University Central Hospital, Helsinki (3) Leiras Oy Clinical Research, Helsinki and (4) Department of Internal Medicine, Seinajoki Central Hospital, Seinajoki, Finland, FI Article note: Received: 4 March 2002 / Accepted: 9 July 2002

Presents a study that re-evaluated the bone mineral density (BMD) and bone turnover state at a median of six years after bone marrow transplantation. Vitamin D status of the patients; Effect of the treatment with methylprednisolone or cyclosporine A on changes in BMD; Reasons for bone loss after organ transplants.