Rouleau Coline, Malorie Margaux, Collet Corinne, Porquet-Bordes Valérie, Gennero Isabelle, Eddiry Sanaa, Laroche Michel, Salles Jean Pierre, Couture Guillaume, Edouard Thomas
Endocrine, Bone Diseases and Genetics Unit, Reference Centre for Rare Diseases of Calcium and Phosphate Metabolism, ERN BOND, OSCAR Network, Paediatric Research Unit, Children's Hospital, Toulouse University Hospital, Toulouse, France.
Department of Rheumatology, Toulouse University Hospital, Toulouse, France.
Bone Rep. 2022 Feb 23;16:101176. doi: 10.1016/j.bonr.2022.101176. eCollection 2022 Jun.
To describe the presenting features, bone characteristics and molecular genetics in a large monocentric cohort of children and young adults with idiopathic primary osteoporosis.
Sixty-six patients (19 children, 47 adults; 28 males, 38 females; age at referral: 3.8 to 65 years) diagnosed with primary osteoporosis were included in this study; patients with features of osteogenesis imperfecta or other known syndromes associated with osteoporosis were excluded. For each patient, the following data were collected by retrospective chart review: family and personal history of fracture and osteoporosis, mineral homeostasis parameters and markers of bone formation and resorption, bone mineral density (BMD) of the lumbar spine (LS-BMD), the total body less head (TB-BMD), and total hip levels (TH-BMD) measured by DXA. As part of the initial assessment process, a bone fragility gene panel sequencing was performed in all of these patients.
There was a higher predominance of males in the children (63%) and of females in the adults (66%) (p = 0.030). Compared to the adults, the children had a significantly lower frequency of vertebral fractures (26 57%, p = 0.022) and a higher frequency of peripheral fractures (84 53%; p = 0.019). Bone fragility gene panel sequencing allowed the identification of the heterozygous pathogenic variant in 27% of patients (most frequently in , and or genes) and the heterozygous p.(Val667Met) variant in 11% of them. The frequency of pathogenic variants tended to be higher in the children compared to the adults without reaching statistical significance (42 19%; p = 0.053). The frequency of the p.(Val667Met) variant was similar in children and adults. No significant differences were found regarding the various clinical, biological and radiological characteristics of the patients according to genotype.
In this study, we reported the presenting features and bone characteristics in a large cohort of children and young adults with idiopathic primary osteoporosis. Bone fragility gene panel sequencing allowed the identification of genetic variants in a significant proportion of these patients. Molecular diagnosis in these patients is important in order to be able to offer genetic counselling and organise patient management.
描述一大组患有特发性原发性骨质疏松症的儿童和青年成人的临床表现、骨骼特征及分子遗传学情况。
本研究纳入66例诊断为原发性骨质疏松症的患者（19例儿童，47例成人；28例男性，38例女性；就诊年龄3.8至65岁）；排除具有成骨不全特征或其他已知与骨质疏松症相关综合征的患者。通过回顾病历，收集每位患者以下数据：骨折和骨质疏松症的家族史及个人史、矿物质稳态参数以及骨形成和骨吸收标志物、腰椎骨密度（LS - BMD）、全身除头部骨密度（TB - BMD）以及通过双能X线吸收法测量的全髋部骨密度（TH - BMD）。作为初始评估过程的一部分，对所有这些患者进行了骨脆性基因panel测序。
儿童中男性占比更高（63%），成人中女性占比更高（66%）（p = 0.030）。与成人相比，儿童椎体骨折发生率显著更低（26%对57%，p = 0.022），外周骨折发生率更高（84%对53%；p = 0.019）。骨脆性基因panel测序在27%的患者中鉴定出杂合致病性变异（最常见于 、 和 或 基因），11%的患者中鉴定出杂合p.(Val667Met)变异。与成人相比，儿童中致病性变异的频率有更高趋势，但未达到统计学显著性（42%对19%；p = 0.053）。儿童和成人中p.(Val667Met)变异的频率相似。根据基因型，患者的各种临床、生物学和放射学特征未发现显著差异。
在本研究中，我们报告了一大组患有特发性原发性骨质疏松症的儿童和青年成人的临床表现和骨骼特征。骨脆性基因panel测序能够在相当比例的这些患者中鉴定出遗传变异。对这些患者进行分子诊断对于提供遗传咨询和组织患者管理很重要。
