# Post-translational modifications of collagen type I in osteogenesis imperfecta: Systematic review and meta-analysis

## TL;DR

This study reviews how collagen type I in osteogenesis imperfecta is chemically altered, finding increased modifications in certain tissues and severe cases.

## Contribution

The study systematically quantifies post-translational modifications in collagen-I from osteogenesis imperfecta patients, revealing tissue-specific and severity-related patterns.

## Key findings

- Hydroxylysine and glycosylation levels are increased in OI collagen-I, while hydroxyproline remains unchanged.
- Collagen-I modifications are more pronounced in bone-derived samples compared to skin or dentine.
- Severe OI cases (type 2) show the highest levels of hydroxylysine and glycosylation.

## Abstract

Osteogenesis imperfecta (OI) is a rare genetic disorder most often caused by mutations in genes that encode collagen type I. OI collagen-I differs from healthy collagen-I due to the underlying mutation and altered post-translational modifications (PTMs). The objective of this study was to use knowledge synthesis to quantify the levels of selected PTMs, hydroxylysine (HYL), hydroxyproline (HYP) and glycosylation (GLY) in OI collagen-I. A systematic search in Medline, Ovid and Web of Science, identified 701 studies reporting on PTM outcomes for OI patients with collagen-I mutation. We excluded animal studies, and reports for OI patients with mutations other than in collagen-I. After screening, we included 36 qualitative studies and 25 quantitative studies for meta-analysis. All qualitative studies reported that OI collagen-I was overmodified. Meta-analysis of studies with quantitative data was performed using normalized mean difference as a study-level effect size and a random-effects model with the Hunter and Smith with sample size correction. The hydroxylysine dataset included 150 patients across 20 studies and had an effect size of 0.33 (confidence interval (CI) 0.21, 0.45). HYL levels were higher in bone-derived collagen-I than in fibroblast- or dentine-derived. The hydroxyproline dataset included 141 patients across 17 studies and had an effect size of 0.00 (CI: −0.02, 0.02). The glycosylation dataset included 17 patients across 5 studies and had an effect size of 0.55 (CI: 0.38, 0.71). Patients with the most severe form of OI (type 2) had the highest levels of collagen-I HYL and GLY. Our study provides new insights into collagen-I pathophysiology in OI, generating new hypotheses regarding the role of PTM in mediating disease presentation in different tissues and overall severity.

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•Mutations and biochemical changes alter collagen-I in osteogenesis imperfecta.•Post-translational modifications analyzed across 66 studies, 269 patients.•Hydroxylysine and glycosylation increased; hydroxyproline unchanged in OI collagen-I.•Collagen-I more modified in bone than in skin/dentine, and in severe OI cases.•Altered collagen may explain tissue-specific disease patterns and severity.

Mutations and biochemical changes alter collagen-I in osteogenesis imperfecta.

Post-translational modifications analyzed across 66 studies, 269 patients.

Hydroxylysine and glycosylation increased; hydroxyproline unchanged in OI collagen-I.

Collagen-I more modified in bone than in skin/dentine, and in severe OI cases.

Altered collagen may explain tissue-specific disease patterns and severity.