Center for Rare Diseases Ruhr CeSER, Ruhr-University Bochum and Witten/Herdecke University, Bochum, Germany.
Department of Pediatrics II, University Hospital Essen and University of Duisburg-Essen, Essen, Germany.
Horm Res Paediatr. 2021;94(3-4):151-158. doi: 10.1159/000517164. Epub 2021 Jul 14.
In ultra-rare bone diseases, information on growth during childhood is sparse. Juvenile Paget disease (JPD) is an ultra-rare disease, characterized by loss of function of osteoprotegerin (OPG). OPG inhibits osteoclast activation via the receptor activator of nuclear factor-κB (RANK) pathway. In JPD, overactive osteoclasts result in inflammatory-like bone disease due to grossly elevated bone resorption. Knowledge on the natural history of JPD, including final height and growth, is limited. Most affected children receive long-term antiresorptive treatment, mostly with bisphosphonates, to contain bone resorption, which may affect growth. In this study, we report the follow-up of height, growth velocity, and skeletal maturation in a 16-year-old female patient with JPD. The patient was treated with cyclic doses of pamidronate starting at 2.5 years of age and with 2 doses of denosumab at the age of 8 years, when pamidronate was paused. In the following years, a sustainable decline in a height z-score and a stunted pubertal growth spurt; despite appropriate maturation of the epiphyseal plates of the left hand, the proximal right humerus and both femora were observed. Whether this reflects the growth pattern in JPD or might be associated to the antiresorptive treatments is unclear, since there is very limited information available on the effect of bisphosphonates and denosumab on growth and the growth plate in pediatric patients. Studies are needed to understand the natural history of an ultra-rare bone disease and to assess the effects of antiresorptive treatment on the growing skeleton.
在超罕见的骨骼疾病中，关于儿童时期生长的信息较为匮乏。青少年 Pagets 病（juvenile Paget disease，JPD）是一种超罕见疾病，其特征为骨保护素（osteoprotegerin，OPG）功能丧失。OPG 通过核因子-κB 受体激活物（receptor activator of nuclear factor-κB，RANK）通路抑制破骨细胞的激活。在 JPD 中，破骨细胞过度活跃导致炎症样骨病，原因是骨吸收明显增加。关于 JPD 的自然病史，包括最终身高和生长，知之甚少。大多数受影响的儿童接受长期抗吸收治疗，主要使用双膦酸盐，以控制骨吸收，这可能会影响生长。在这项研究中，我们报告了一名 16 岁女性 JPD 患者的身高、生长速度和骨骼成熟度的随访情况。该患者从 2.5 岁开始接受周期性帕米膦酸盐治疗，8 岁时接受了 2 次地舒单抗治疗，随后暂停了帕米膦酸盐治疗。在随后的几年中，身高 z 评分持续下降，青春期生长突增受到限制；尽管左手骨骺板适当成熟，但右侧肱骨近端和双侧股骨均观察到发育不良。这是否反映了 JPD 的生长模式，或者是否与抗吸收治疗有关尚不清楚，因为关于双膦酸盐和地舒单抗对儿科患者生长和生长板的影响的信息非常有限。需要开展研究以了解超罕见骨骼疾病的自然病史，并评估抗吸收治疗对生长中骨骼的影响。
