Supplementary Material for: Outcomes of Zoledronic Acid Use in Paediatric Conditions

<b><i>Introduction:</i></b> Limited evidence is available concerning experience with use of zoledronic acid (ZA) and treatment for conditions other than primary bone fragility. <b><i>Materials and Methods:</i></b> A retrospective review of all Royal Children Hospital patients who had been administered at least 1 dose of intravenous ZA from 2002 to 2015 was undertaken. <b><i>Results:</i></b> The audit included 309 children with 228 being treated for bone fragility conditions. Of the 228, 68 had height-adjusted lumbar spine bone mineral density Z-scores available over up to a 5-year period, and median increases were +2.0 SD (median absolute deviation = 0.9) (<i>N</i> = 36, <i>p</i> value for median increase of at least 0.5 in Z-score &lt;0.001), for patients with osteogenesis imperfecta or other primary bone fragility disorders, +1.0 SD (0.9) (<i>N</i> = 14, <i>p</i> = 0.029), for immobility conditions, +0.5 SD (0.7) (<i>N</i> = 10, <i>p</i> = 0.399), and for glucocorticoid-induced secondary osteoporosis, +0.7 SD (0.6) (<i>N</i> = 8, <i>p</i> = 0.015). 81/309 children were treated for bone abnormality indications (e.g., avascular necrosis [AVN], fibrous dysplasia, and bone cysts). Of 39 with AVN, outcome data were available for 33, with joint integrity maintained for 24/33 from 6 to 24 months after last ZA, subjective reports (22/28) of reduced pain. Reduction in bone lesion size was seen in 2/4 patients with bone cysts within 12 months of ZA commencement. <b><i>Discussion/Conclusion:</i></b> This is the largest cohort of reported outcomes of ZA use in a paediatric population. Results demonstrate a good efficacy profile and associated improved bone density for osteoporotic conditions and stabilization of non-traumatic AVN with a low rate of joint collapse.

<b><i>引言：</i></b> 目前针对唑来膦酸（zoledronic acid, ZA）在原发性骨脆性以外疾病中的应用经验，相关研究证据十分有限。<b><i>材料与方法：</i></b> 本研究对2002年至2015年间，于皇家儿童医院接受至少1剂静脉输注唑来膦酸的所有患儿开展了回顾性审查。<b><i>结果：</i></b> 本次审查共纳入309名儿童患者，其中228名因骨脆性相关疾病接受治疗。在该228名患者中，68名在最长5年随访周期内拥有身高校正的腰椎骨密度Z评分数据：成骨不全或其他原发性骨脆性疾病患者的Z评分中位数升高2.0个标准差（中位数绝对偏差=0.9，N=36，Z评分至少升高0.5的中位数差异检验p<0.001）；制动相关疾病患者升高1.0个标准差（0.9，N=14，p=0.029）；糖皮质激素诱导的继发性骨质疏松症患者升高0.7个标准差（0.6，N=8，p=0.015）。另有81名患儿因骨异常相关指征接受治疗，涵盖缺血性坏死（avascular necrosis, AVN）、纤维异常增殖症与骨囊肿等病症。在39名缺血性坏死患者中，33名拥有转归数据：末次输注唑来膦酸后6至24个月随访显示，33名中的24名关节完整性得以维持；28名患者主观报告疼痛缓解（22/28）。在4名骨囊肿患者中，2名在开始唑来膦酸治疗后12个月内观察到骨病灶体积缩小。<b><i>讨论与结论：</i></b> 本研究为目前已报道的最大规模儿童人群唑来膦酸应用转归队列。结果显示，唑来膦酸在骨质疏松性疾病中具备良好的疗效谱，可有效提升骨密度，同时能稳定非创伤性缺血性坏死患者的病情，且关节塌陷发生率较低。