Sustained beneficial effect of intravenous bisphosphonates after their discontinuation in children

We studied if the beneficial effects of bisphosphonates are maintained after their discontinuation, and whether adverse effects may develop. Seventeen children in whom I.V. bisphosphonates were discontinued for at least 12 months were included. Fracture rate (FR), skeletal pain, bone mineral density of total body (TB) and spine L2-4, skeletal radiographs, bone markers and kidney functions were compared between: (a) before treatment, (b) end of treatment, and (c) last follow-up. Mean treatment duration was 22 +/- 2 months (6-43) and follow-up 26 +/- 2 months (18-44). FR (mean +/- SD) decreased from 0.74 +/- 0.21/year before treatment to 0.35 +/- 0.11/year after treatment and 0.20 +/- 0.09/year at follow-up (p < 0.05). Three children had bone pain before treatment, six during treatment and none at end of follow-up (p < 0.05). TB Z-score increased from -1.24 +/- 0.50 at baseline to -0.37 +/- 0.44 at end of treatment and -0.39 +/- 0.37 at follow-up (p < 0.05). Spinal Z-score increased from -1.65 +/- 0.57 to -0.34 +/- 0.56 and 0.19 +/- 0.49, respectively (p < 0.05). Bone turnover markers showed sustained effect of bisphosphonates. No adverse effects on kidney functions or skeletal radiographs were noted. We conclude that I.V. bisphosphonates continue to exert their beneficial effect for a mean of 26 +/- 2 months after their discontinuation; therefore, once therapeutic goals are achieved, the medication can be withheld, followed by periodic re-evaluation.