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Summary <p>In 115 adult patients with classical OI, reduced bone structure was observed in patients with <i>COL1A1</i> variants compared to those with <i>COL1A2</i> variants. In addition, bone structure in the distal radius was differentially affected in individuals with quantitative <i>COL1A1/2</i> variants in comparison to patients carrying qualitative variants.</p> Purpose <p>Classical osteogenesis imperfecta (OI) is genetically determined by pathogenic variants in the <i>COL1A1/2</i> genes encoding collagen type I. Although genetic testing is widely used today, the genotype–phenotype correlation is still a matter of debate.</p> Methods <p>A retrospective analysis was carried out in a total of 115 adult OI patients who presented to our outpatient clinic. Only patients with available genetic test results and clinically diagnosed OI were included. Biochemical parameters, bone density (DXA), and bone microstructure (HR-pQCT) were assessed and compared between genotype variants.</p> Results <p>Overall, 71 patients showed (likely) pathogenic variants in the <i>COL1A1</i> and 44 in the <i>COL1A2</i> gene. Forty-six variants were predicted as causing quantitative and 58 as causing qualitative effects, whereas the potential effect of 11 variants could not be predicted. <i>COL1A1</i> variants were associated with significantly lower trabecular bone mineral density (Tb.BMD) and bone volume fraction (BV/TV) compared to <i>COL1A2</i> variants both at the radius (Tb.BMD: <i>p</i> = <i>0.008</i>; BV/TV: <i>p</i> = <i>0.010</i>) and tibia (Tb.BMD: <i>p</i> = <i>0.015</i>; BV/TV: <i>p</i> = <i>0.028</i>). In addition, trabecular parameters only in the distal radius were significantly (<i>p</i> &lt; <i>0.05</i>) reduced in patients with quantitative variants in comparison to patients with qualitative variants. OI type I patients had significantly higher cortical bone mineral density (Ct.BMD) than type III. No other microstructural differences were found between the types I, III, and IV.</p> Conclusions <p>Genetic stratification in adult OI patients revealed differences in bone microstructure, while these were absent when individuals were grouped according OI types (Sillence classification). Future studies are needed to further investigate the genotype–phenotype correlation in patients with classical OI.</p>

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Genotype-based comparison of bone microstructure in adult patients with classical osteogenesis imperfecta

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  • 发表日期：

    2025年12月9日

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  • Mikolaj Bartosik,
  • Mascha Prengel,
  • Julian Delsmann,
  • Julia Oswald,
  • Uwe Kornak,
  • Florian Barvencik,
  • Thorsten Schinke,
  • Michael Amling,
  • Ralf Oheim

摘要

Summary

In 115 adult patients with classical OI, reduced bone structure was observed in patients with COL1A1 variants compared to those with COL1A2 variants. In addition, bone structure in the distal radius was differentially affected in individuals with quantitative COL1A1/2 variants in comparison to patients carrying qualitative variants.

Purpose

Classical osteogenesis imperfecta (OI) is genetically determined by pathogenic variants in the COL1A1/2 genes encoding collagen type I. Although genetic testing is widely used today, the genotype–phenotype correlation is still a matter of debate.

Methods

A retrospective analysis was carried out in a total of 115 adult OI patients who presented to our outpatient clinic. Only patients with available genetic test results and clinically diagnosed OI were included. Biochemical parameters, bone density (DXA), and bone microstructure (HR-pQCT) were assessed and compared between genotype variants.

Results

Overall, 71 patients showed (likely) pathogenic variants in the COL1A1 and 44 in the COL1A2 gene. Forty-six variants were predicted as causing quantitative and 58 as causing qualitative effects, whereas the potential effect of 11 variants could not be predicted. COL1A1 variants were associated with significantly lower trabecular bone mineral density (Tb.BMD) and bone volume fraction (BV/TV) compared to COL1A2 variants both at the radius (Tb.BMD: p = 0.008; BV/TV: p = 0.010) and tibia (Tb.BMD: p = 0.015; BV/TV: p = 0.028). In addition, trabecular parameters only in the distal radius were significantly (p < 0.05) reduced in patients with quantitative variants in comparison to patients with qualitative variants. OI type I patients had significantly higher cortical bone mineral density (Ct.BMD) than type III. No other microstructural differences were found between the types I, III, and IV.

Conclusions

Genetic stratification in adult OI patients revealed differences in bone microstructure, while these were absent when individuals were grouped according OI types (Sillence classification). Future studies are needed to further investigate the genotype–phenotype correlation in patients with classical OI.