Rooney Madeleine, Bishop Nick, Davidson Joyce, Beresford Michael W, Pilkington Clarissa, Donagh Janet Mc, Wyatt Sue, Gardner-Medwin Janet, Satyapal Rangaraj, Clinch Jacqui, Foster Helen, Elliott Mark, Verghis Rejina
Queens University of Belfast and Musgrave Park Hospital Belfast Hospital Trust, United Kingdom of Great Britain and Northern Ireland.
University of Sheffield and Sheffield Children's NHS Foundation Trust, United Kingdom of Great Britain and Northern Ireland.
EClinicalMedicine. 2019 Jul 3;12:79-87. doi: 10.1016/j.eclinm.2019.06.004. eCollection 2019 Jul.
Children and young people (CYP) with chronic rheumatic conditions; Juvenile Idiopathic Arthritis, Juvenile Systemic Lupus Erythematosus, Juvenile Dermatomyositis and Juvenile Vasculitis, treated with steroids, have low bone density, increased fracture risk and are likely to have suboptimal peak bone mass. There is currently no evidence base for the management of steroid-induced bone loss in children with rheumatic diseases.
We undertook a multi-centre double dummy double-blind randomised placebo controlled trial to investigate whether the bisphosphonate risedronate was superior to alfacalcidol or calcium and vitamin D supplementation in the prevention and treatment of steroid-induced osteopaenia in these children. Patients were stratified and randomised in a 1:1 ratio, into: placebo; alfacalcidol; risedronate. The primary outcome was the change in lumbar spine bone mineral density z score (LSaBMDz) measured by dual energy x-ray absorptiometry at one year. Secondary outcome was fracture rate.
Two hundred and seventeen patients were recruited to the study. Seventy seven placebo, 71 alfacalcidol, and 69 risedronate. Highly statistically significant differences were observed in the change in LSaBMDz between the placebo and risedronate groups; 0.274, 95% CI (0.061, 0.487) (p < 0.001) and between the risedronate and the alfacalcidol groups; 0.326 95% CI (0.109, 0.543) (p < 0.001). The difference observed between the alfacalcidol and placebo group was not statistically significant.Highly statistically significant differences were seen in the change in Total Body Less Head aBMD-Z Score between the placebo and risedronate groups (p < 0.01) but not between the alfacalcidol and risedronate groups. No significant differences in fracture frequency, adverse or serious adverse reactions were observed between the groups.
Children and adolescents receiving steroids for rheumatic diseases benefit from prophylactic treatment with bisphosphonates to increase LSaBMD. Alfacalcidol is ineffective.
患有慢性风湿性疾病的儿童和青少年(CYP),如幼年特发性关节炎、幼年系统性红斑狼疮、幼年皮肌炎和幼年血管炎,接受类固醇治疗后,骨密度较低,骨折风险增加,且峰值骨量可能不理想。目前尚无关于风湿性疾病患儿类固醇诱导性骨质流失管理的证据基础。
我们进行了一项多中心双模拟双盲随机安慰剂对照试验,以研究双膦酸盐利塞膦酸盐在预防和治疗这些儿童类固醇诱导性骨质减少方面是否优于阿法骨化醇或钙和维生素D补充剂。患者按1:1比例分层随机分为:安慰剂组;阿法骨化醇组;利塞膦酸盐组。主要结局是一年时通过双能X线吸收法测量的腰椎骨矿物质密度z评分(LSaBMDz)的变化。次要结局是骨折发生率。
217名患者被纳入研究。77名接受安慰剂,71名接受阿法骨化醇,69名接受利塞膦酸盐。在安慰剂组和利塞膦酸盐组之间观察到LSaBMDz变化有高度统计学显著差异;0.274,95%可信区间(0.061,0.487)(p<0.001),在利塞膦酸盐组和阿法骨化醇组之间也有差异;0.326,95%可信区间(0.109,0.543)(p<0.001)。阿法骨化醇组和安慰剂组之间观察到的差异无统计学意义。在安慰剂组和利塞膦酸盐组之间观察到全身去头aBMD-Z评分变化有高度统计学显著差异(p<0.01),但在阿法骨化醇组和利塞膦酸盐组之间没有。各组之间在骨折频率、不良或严重不良反应方面未观察到显著差异。
接受类固醇治疗的风湿性疾病儿童和青少年受益于双膦酸盐的预防性治疗以增加LSaBMD。阿法骨化醇无效。