SUN-LB66 Oral Risedronate Treatment in Children With Osteogenesis Imperfecta

Introduction: To date, there are no approved pharmaceutical therapies for children with OI. Intravenous bisphosphonates have been used for years to treat children with OI with variable efficacy and tolerability. However, a few studies have evaluated the effects and tolerability of oral risedronate in children with OI (1)(2). In this study, we aimed to present our experience with oral risedronate treatment in children with OI. Methods: A retrospective chart review of patients with OI and history of multiple fragility fractures, who were treated with oral risedronate and followed in our bone clinic between the years of 2013 and 2019. Primary outcomes included changes in fracture rate, urinary N-terminal telopeptide (uNTX), height z-scores, and lumbar and femur BMD z-scores. Safety and tolerability of risedronate were reviewed. Wilcoxon matched-pairs sign-ranks test was used to assess the medians (IQR) between pre- and post-treatment with p value of < 0.05 set as statistically significant.Results: A total of 17 patients ages 5—19 ys were reviewed (11 males, 65% type I OI, 12% type III, 18% type XI, and 5% unknown). At the time of the review, 69% were on weekly, 19% on daily, and 12% on monthly risedronate treatment. Mean duration of therapy was 2.7 y ± 2.3 y, ranging 0.5 to 8 ys. The bone resorption marker, uNTX, decreased > 30% from baseline in 93% of subjects within the first year of treatment, and was statistically lower by the end of treatment period [245 (159, 393) to 170 (39, 261), p=0.02]. Height z-score did not change with treatment, -0.80 (-1.20, 0.10) pre- and -0.85 (-1.60, -0.40) post-treatment, p = 0.2 in patients with Type I OI. There was a clinically significant reduction in the rate of fractures from baseline 0.6 per y (0.4, 0.8) to 0.24 (0, 0.5) by the end of the treatment period, though it did not reach statistical significance. Within a year of treatment, 80% of children were fracture free with improvement in bone pain and mobility. BMD pre- and on treatment for lumbar and femur were -2.5 (-3.43, -1.94) and -2.36 (-3.25, -1.35), and -2.05 (-2.95, 0.3) and -1.18 (-1.73, 2.13), respectively. However, there was no statistical significance. There was one case of reflux without erosive esophagitis, which resolved with reflux treatment. Overall, risedronate was well tolerated with no cases of clinically significant acute phase reaction, hypocalcemia, erosive esophagitis, or osteonecrosis of the jaw.Conclusion: Based on our experience, oral risedronate effectively decreased bone resorption, showed a trend towards decrease in fracture rate with improvement in symptoms, and was well tolerated in children with OI. More data are needed to systematically evaluate its long-term effects on growth, bone mineral density, fracture frequency, and quality of life in children with different types of OI. Reference: (1) Rauch et al., J Bone Miner Res. 2009; 24: 1282-1289 (2) Bishop et al., Lancet. 2013;382(9902):1424-32.