Nonsustained effect of short-term bisphosphonate therapy on bone turnover three years after renal transplantation

BACKGROUND: We recently showed that two doses of 4 mg of zoledronic acid (ZOL) ameliorated the bone loss and improved bone histology within the first six months after kidney transplantation. The aim of the present study was to evaluate whether this early short-term intervention exhibited a sustained bone-sparing effect. METHODS: A homogenous group of 20 de novo renal transplant recipients were equally randomized to two infusions of 4 mg of ZOL or placebo at two weeks and three months after engraftment. Patients were followed up for three years by sequential determination of bone densitometry and specific biochemical markers. RESULTS: From month six to three years after transplantation, both treatment groups exhibited an improvement of bone mineralization. Femoral neck bone mineral density z-scores increased statistically significantly from -1.3 (2.6) to -0.2 (3.6) in the placebo group and from -1.6 (2.9) to -1.2 (1.9) in the ZOL group (median, range). Biochemical parameters of osteoblast activity such as osteocalcin and bone-specific alkaline phosphatase did not increase significantly in both groups. Osteoprotegerin, a marker of osteoclast inhibition, was significantly elevated over the first six months in the ZOL group, but decreased to similar levels, as in the placebo group, over the next two and a half years. Other markers of osteoclast activity such as c-telopeptide of type 1 collagen, calcitonin, and intact parathyroid hormone were not different between six months and three years in either group. CONCLUSION: The early bone-sparing effect of short-term ZOL therapy confers no sustained benefit versus placebo at three year post-transplantation.