Risedronate in the Treatment of Mild Pediatric Osteogenesis Imperfecta: A Randomized Placebo-Controlled Study
Risedronate in the Treatment of Mild Pediatric Osteogenesis Imperfecta: A Randomized Placebo-Controlled Study
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DOI：
10.1359/jbmr.090213
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发表时间：
2009-07-01
影响因子：
6.2
通讯作者：
Glorieux, Francis H.
中科院分区：
文献类型：
--
作者：
Rauch, Frank;Munns, Craig F.;Glorieux, Francis H.
静脉注射帕米膦酸钠是最广泛用于治疗中度至重度骨发育不全症。(OI)。目前，没有针对轻度成骨不全患者的药物治疗方法。我们进行了一项单中心随机双盲安慰剂对照试验，以检验口服利塞膦酸钠治疗小儿轻度成骨不全症的疗效和安全性。共有26名I型成骨不全的儿童和青少年（年龄6.1-17.7岁，其中11名女孩）被随机分配到安慰剂组（N = 13）或利塞膦酸盐组（N = 13），持续2年。体重40公斤的患者，利塞膦酸盐剂量为15 mg，每周1次。治疗2年后，利塞膦酸钠降低血清骨吸收标志物I型胶原n端肽水平35%，而安慰剂降低6% （P = 0.003）。利塞膦酸钠使腰椎面积BMD z评分增加0.65，而接受安慰剂的患者则减少0.15 （p = 0.002）。相比之下，桡骨干骺端和骨干、髋部和全身的骨量和骨密度没有明显的治疗差异。研究期结束时经髂骨活检的组织形态计量学分析未显示治疗在皮质宽度、骨小梁体积或骨转换参数方面有显著差异。同样，在椎体形态测量、第二掌骨皮质宽度、握力、骨痛或新骨折数量方面也没有检测到治疗效果。安全性方面，利塞膦酸钠总体耐受性良好，各治疗组的临床或实验室不良反应发生率相似。这些结果表明口服利塞膦酸钠对骨骼的影响弱于静脉注射帕米膦酸钠治疗，但仍会导致腰椎面积骨密度的增加。未来的研究应探讨口服利塞膦酸钠是否能有效降低轻度成骨不全儿童和青少年的骨折发生率[J] .骨外科杂志，2009;24:1282-1289。2009年2月16日在线发布；doi: 10.1359 / JBMR.090213
Intravenous pamidronate is the most widely used treatment for moderate to severe osteo-agenesis imperfecta. (OI). Currently, there is no medical treatment for patients with mild OI. We conducted a single-center randomized double-blind placebo-controlled trial to examine the efficacy and safety of oral risedronate in the treatment of pediatric patients with mild OI. A total of 26 children and adolescents (age, 6.1-17.7 yr; 11 girls) with OI type I were randomized to either placebo (N = 13) or risedronate (N = 13) for 2 yr. Risedronate doses were 15 mg once per week in patients weighing 40 kg. After 2 yr of treatment, risedronate decreased serum levels of the bone resorption marker collagen type I N-telopeptide by 35% compared with a 6% reduction with placebo (P = 0.003). Risedronate increased lumbar spine areal BMD Z-scores by 0.65, whereas patients receiving placebo experienced a decrease of 0.15 (p = 0.002). In contrast, no significant treatment differences in bone mass and density were found at the radial metaphysis and diaphysis, the hip, and the total body. Histomorphometric analysis of transiliac bone biopsies at the end of the study period did not show a significant treatment difference in cortical width, trabecular bone volume, or parameters of bone turnover. Similarly, there was no detectable treatment effect on vertebral morphometry, second metacarpal cortical width, grip force, bone pain, or number of new fractures. Regarding safety, risedronate was generally well tolerated, and the incidence of clinical or laboratory adverse experiences was similar among treatment groups. These results suggest that the skeletal effects of oral risedronate are weaker than those that are commonly observed with intravenous pamidronate treatment but still lead to an increase in lumbar spine areal BMD. Future studies should investigate whether oral risedronate is effective in reducing fracture rates in children and adolescents with mild OI type I. J Bone Miner Res 2009;24:1282-1289. Published online on February 16, 2009; doi: 10.1359/JBMR.090213