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. 2022 Feb 23:16:101176.
doi: 10.1016/j.bonr.2022.101176. eCollection 2022 Jun.

Diagnostic yield of bone fragility gene panel sequencing in children and young adults referred for idiopathic primary osteoporosis at a single regional reference centre

Coline Rouleau  1 , Margaux Malorie  2 , Corinne Collet  3 , Valérie Porquet-Bordes  1 , Isabelle Gennero  4 , Sanaa Eddiry  1 , Michel Laroche  2 , Jean Pierre Salles  1 , Guillaume Couture  2 , Thomas Edouard  1
Affiliations

Diagnostic yield of bone fragility gene panel sequencing in children and young adults referred for idiopathic primary osteoporosis at a single regional reference centre

Coline Rouleau et al. Bone Rep. .

Abstract

Aim: To describe the presenting features, bone characteristics and molecular genetics in a large monocentric cohort of children and young adults with idiopathic primary osteoporosis.

Methods: 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.

Results: 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 vs 57%, p = 0.022) and a higher frequency of peripheral fractures (84 vs 53%; p = 0.019). Bone fragility gene panel sequencing allowed the identification of the heterozygous pathogenic variant in 27% of patients (most frequently in LRP5, WNT1 and COL1A1 or 2 genes) and the heterozygous p.(Val667Met) LRP5 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 vs 19%; p = 0.053). The frequency of the p.(Val667Met) LRP5 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.

Conclusion: 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.

Keywords: Bone mineral density; DXA; Early-onset osteoporosis; Idiopathic juvenile osteoporosis; Primary osteoporosis.

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Conflict of interest statement

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Figures

Fig. 1
Fig. 1
Distribution of gene variants in all patients (A) children (B) and adults (C) with idiopathic primary osteoporosis Absence or presence of non-pathogenic variants are represented in white, variant of unknown significance (VUS) in grey, p.(Val667Met) LRP5 variant in orange and pathogenic variants in blue/green. If a patient had two variants, the most pathogenic was taken into account when classifying the mutations.
See this image and copyright information in PMC

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