Non-Cochrane · other · PM41531674
Post-translational modifications of collagen type I in osteogenesis imperfecta: Systematic review and meta-analysis.
Patel Priyesh, Aksornthong Sirion, Komarova Svetlana V · Bone reports · 2026 · PubMed · doi:10.1016/j.bonr.2025.101894
Findings
Population Patients with osteogenesis imperfecta (OI) caused by collagen type I mutations
8 findings
| OI collagen-I (patient-derived bone, fibroblast or dentine samples) | Control (healthy) collagen-I | Ratio of hydroxylysine to hydroxyproline (HYL/HYP) in collagen-I Collagen-I biochemistry of patient samples versus controls (random-effects, Hunter-Schmidt estimator) | Normalized mean difference 0.22 [0.19, 0.25] GRADE not reported 10 studies · 96 participants |
| OI collagen-I (patient-derived bone, fibroblast or dentine samples) | Control (healthy) collagen-I | Hydroxyproline (HYP) percentage in collagen-I Collagen-I biochemistry of patient samples versus controls (random-effects, Hunter-Schmidt estimator) · Sample origin: dentine | Printed in Figure 3A as 0.01 [ 0.03, 0.01] (signs not legible); I2 6.0%, tau2 0.00; test for subgroup difference QM 3.37, df 1 GRADE not reported 3 studies · 62 participants |
| OI collagen-I (patient-derived bone, fibroblast or dentine samples) | Control (healthy) collagen-I | Glycosylation ratio (diglycosylated/monoglycosylated hydroxylysine, GGHYL/GHYL) in collagen-I Collagen-I biochemistry of patient samples versus controls (random-effects, Hunter-Schmidt estimator) | Normalized mean difference 0.55 [0.38, 0.71] GRADE not reported 5 studies · 17 participants |
| OI collagen-I (patient-derived bone, fibroblast or dentine samples) | Control (healthy) collagen-I | Hydroxylysine (HYL) percentage in collagen-I Collagen-I biochemistry of patient samples versus controls (random-effects, Hunter-Schmidt estimator) · Sample origin: dentine | Normalized mean difference 0.09 [-0.01, 0.19] GRADE not reported 3 studies · 62 participants |
| OI collagen-I (patient-derived bone, fibroblast or dentine samples) | Control (healthy) collagen-I | Hydroxyproline (HYP) percentage in collagen-I Collagen-I biochemistry of patient samples versus controls (random-effects, Hunter-Schmidt estimator) · Sample origin: bone and fibroblast | Normalized mean difference 0.01 [-0.01, 0.03] GRADE not reported 14 studies · 79 participants |
| OI collagen-I (patient-derived bone, fibroblast or dentine samples) | Control (healthy) collagen-I | Hydroxyproline (HYP) percentage in collagen-I Collagen-I biochemistry of patient samples versus controls (random-effects, Hunter-Schmidt estimator) | Normalized mean difference 0.00 [-0.02, 0.02] GRADE not reported 17 studies · 141 participants |
| OI collagen-I (patient-derived bone, fibroblast or dentine samples) | Control (healthy) collagen-I | Hydroxylysine (HYL) percentage in collagen-I Collagen-I biochemistry of patient samples versus controls (random-effects, Hunter-Schmidt estimator) | Normalized mean difference 0.33 [0.21, 0.45] GRADE not reported 20 studies · 150 participants |
| OI collagen-I (patient-derived bone, fibroblast or dentine samples) | Control (healthy) collagen-I | Hydroxylysine (HYL) percentage in collagen-I Collagen-I biochemistry of patient samples versus controls (random-effects, Hunter-Schmidt estimator) · Sample origin: bone and fibroblast | Normalized mean difference 0.37 [0.26, 0.49] GRADE not reported 17 studies · 88 participants |
Included primary studies 63
Open in Studies| Study | Year | Also included by | Outcomes it informs here | Trial data |
|---|---|---|---|---|
| Baldwin 1989 A single base mutation that converts glycine 907 of the α2(I) chain of type I procollagen to aspartate in a lethal variant of osteogenesis… DOI:10.1016/s0021-9258(19)81713-1 | 1989 | this review only | not stated | not extracted yet |
| Bank 2000 Pyridinium Cross-Links in Bone of Patients with Osteogenesis Imperfecta: Evidence of a Normal Intrafibrillar Collagen Packing DOI:10.1359/jbmr.2000.15.7.1330 | 2000 | this review only | Hydroxyproline (HYP) percentage in collagen-I | not extracted yet |
| Barnes 2006 Deficiency of Cartilage-Associated Protein in Recessive Lethal Osteogenesis Imperfecta DOI:10.1056/nejmoa063804 | 2006 | this review only | Hydroxylysine (HYL) percentage in collagen-I | not extracted yet |
| Barsh 1981 Reduced secretion of structurally abnormal type I procollagen in a form of osteogenesis imperfecta. DOI:10.1073/pnas.78.8.5142 | 1981 | this review only | not stated | not extracted yet |
| Bateman 1984 Abnormal type I collagen metabolism by cultured fibroblasts in lethal perinatal osteogenesis imperfecta DOI:10.1042/bj2170103 | 1984 | this review only | not stated | not extracted yet |
| Bateman 1987 Lethal perinatal osteogenesis imperfecta due to the substitution of arginine for glycine at residue 391 of the alpha 1(I) chain of type I… DOI:10.1016/s0021-9258(18)48196-3 | 1987 | this review only | not stated | not extracted yet |
| Bateman 1987 A structural mutation of the collagen alpha 1(I)CB7 peptide in lethal perinatal osteogenesis imperfecta. DOI:10.1016/s0021-9258(18)61213-x | 1987 | this review only | not stated | not extracted yet |
| Bateman 1988 Biochemical Heterogeneity of Type I Collagen Mutations in Osteogenesis Imperfecta<sup>a</sup> DOI:10.1111/j.1749-6632.1988.tb55321.x | 1988 | this review only | not stated | not extracted yet |
| Bateman 1991 Characterization of a type I collagen α 2(I) glycine-586 to valine substitution in osteogenesis imperfecta type IV. Detection of the… DOI:10.1042/bj2760765 | 1991 | this review only | not stated | not extracted yet |
| Bateman 1992 Lethal perinatal osteogenesis imperfecta due to a type I collagen α2(I) gly to arg substitution detected by chemical cleavage of an… DOI:10.1002/humu.1380010109 | 1992 | this review only | not stated | not extracted yet |
| Bleckmann 1971 Glykosaminoglykan- und Kollagenanalysen bei Osteogenesis imperfecta DOI:10.1007/bf00446347 | 1971 | this review only | Hydroxylysine (HYL) percentage in collagen-I; Hydroxyproline (HYP) percentage in collagen-I; Ratio of hydroxylysine to hydroxyproline (HYL/HYP) in collagen-I | not extracted yet |
| Brenner 1988 Biochemical Analysis of Bone Compacta in Osteogenesis Imperfecta DOI:10.1111/j.1749-6632.1988.tb55322.x | 1988 | this review only | Ratio of hydroxylysine to hydroxyproline (HYL/HYP) in collagen-I | not extracted yet |
| Brenner 1989 Biochemical analysis of callus tissue in osteogenesis imperfecta type IV. Evidence for transient overmodification in collagen types I and… DOI:10.1172/jci114253 | 1989 | this review only | Ratio of hydroxylysine to hydroxyproline (HYL/HYP) in collagen-I | not extracted yet |
| Brenner 1993 Defective collagen fibril formation and mineralization in osteogenesis imperfecta with congenital joint contractures (Bruck syndrome) DOI:10.1007/bf01955060 | 1993 | this review only | Ratio of hydroxylysine to hydroxyproline (HYL/HYP) in collagen-I | not extracted yet |
| Byers 1988 A novel mutation causes a perinatal lethal form of osteogenesis imperfecta. An insertion in one alpha 1(I) collagen allele (COL1A1). DOI:10.1016/s0021-9258(18)68576-x | 1988 | this review only | not stated | not extracted yet |
| Cabral 2003 Type I Collagen Triplet Duplication Mutation in Lethal Osteogenesis Imperfecta Shifts Register of α Chains throughout the Helix and… DOI:10.1074/jbc.m212523200 | 2003 | this review only | not stated | not extracted yet |
| Cetta 1983 Biochemical Investigations of Different Forms of Osteogenesis Imperfecta. Evaluation of 44 Cases DOI:10.3109/03008208309004847 | 1983 | this review only | Glycosylation ratio (diglycosylated/monoglycosylated hydroxylysine, GGHYL/GHYL) in collagen-I | not extracted yet |
| Constantinos 1989 Lethal osteogenesis imperfecta resulting from a single nucleotide change in one human pro alpha 1(I) collagen allele. DOI:10.1073/pnas.83.16.6045 | 1986 | this review only | not stated | not extracted yet |
| De 1986 The molecular defect in an autosomal dominant form of osteogenesis imperfecta. Synthesis of type I procollagen containing cysteine in the… DOI:10.1016/s0021-9258(19)84487-3 | 1986 | this review only | not stated | not extracted yet |
| Deak 1985 Altered Helical Structure of a Homotrimer of α1(I)Chains Synthesized by Fibroblasts from a Variant of Osteogenesis Imperfecta DOI:10.1016/s0174-173x(85)80020-0 | 1985 | this review only | Hydroxylysine (HYL) percentage in collagen-I; Hydroxyproline (HYP) percentage in collagen-I; Ratio of hydroxylysine to hydroxyproline (HYL/HYP) in collagen-I | not extracted yet |
| Eastoe 1973 The amino-acid composition of human hard tissue collagens in osteogenesis imperfecta and dentinogenesis imperfecta DOI:10.1007/bf02013724 | 1973 | this review only | Hydroxylysine (HYL) percentage in collagen-I; Hydroxyproline (HYP) percentage in collagen-I; Ratio of hydroxylysine to hydroxyproline (HYL/HYP) in collagen-I | not extracted yet |
| Fertala 1993 Two cysteine substitutions in procollagen I: a glycine replacement near the N-terminus of α1(I) chain causes lethal osteogenesis… DOI:10.1042/bj2890195 | 1993 | this review only | not stated | not extracted yet |
| Gage 1988 Abnormal Amino Acid Analyses Obtained from Osteogenesis Imperfecta Dentin DOI:10.1177/00220345880670080701 | 1988 | this review only | Hydroxylysine (HYL) percentage in collagen-I; Hydroxyproline (HYP) percentage in collagen-I | not extracted yet |
| Grange 1990 Analysis Of cultured chorionic villi in a case of osteogenesis imperfecta type II: Implications for prenatal diagnosis DOI:10.1002/ajmg.1320360223 | 1990 | this review only | not stated | not extracted yet |
| Hawkins 1991 matched by author and year (probable) | NR | this review only | not stated | not extracted yet |
| Herbage 1982 Composition, cross-linking and thermal stability of bone and skin collagens in patients with osteogenesis imperfecta DOI:10.1016/0221-8747(82)90022-4 | 1982 | this review only | Hydroxylysine (HYL) percentage in collagen-I; Ratio of hydroxylysine to hydroxyproline (HYL/HYP) in collagen-I | not extracted yet |
| Kirsch 1981 Disorder of collagen metabolism in a patient with osteogenesis imperfecta (lethal type): increased degree of hydroxylation of lysine in… DOI:10.1111/j.1365-2362.1981.tb01763.x | 1981 | this review only | Hydroxylysine (HYL) percentage in collagen-I; Hydroxyproline (HYP) percentage in collagen-I; Ratio of hydroxylysine to hydroxyproline (HYL/HYP) in collagen-I | not extracted yet |
| Kirsch 1983 Analysis of cyanogen bromide peptides of type I collagen from a patient with lethal osteogenesis imperfecta. Overhydroxylation of lysine… DOI:10.1042/bj2110599 | 1983 | this review only | Hydroxylysine (HYL) percentage in collagen-I; Hydroxyproline (HYP) percentage in collagen-I; Ratio of hydroxylysine to hydroxyproline (HYL/HYP) in collagen-I | not extracted yet |
| Kirsch 1987 Compositional analysis of collagen from patients with diverse forms of osteogenesis imperfecta DOI:10.1007/bf02555125 | 1987 | this review only | Hydroxylysine (HYL) percentage in collagen-I | not extracted yet |
| Lehmann 1995 Hydroxylation of collagen type I: evidence that both lysyl and prolyl residues are overhydroxylated in osteogenesis imperfecta DOI:10.1111/j.1365-2362.1995.tb01706.x | 1995 | this review only | Hydroxylysine (HYL) percentage in collagen-I; Hydroxyproline (HYP) percentage in collagen-I | not extracted yet |
| Lightfoot 1994 Substitution of serine for glycine 883 in the triple helix of the pro alpha 1 (I) chain of type I procollagen produces osteogenesis… DOI:10.1016/s0021-9258(18)43820-3 | 1994 | this review only | not stated | not extracted yet |
| Makareeva 2018 Molecular Mechanism of α1(I)-Osteogenesis Imperfecta/Ehlers-Danlos Syndrome DOI:10.1074/jbc.m511830200 | 2006 | this review only | Hydroxylysine (HYL) percentage in collagen-I | not extracted yet |
| Marini 1989 Osteogenesis imperfecta type IV DOI:10.1016/s0021-9258(18)80150-8 | 1989 | this review only | not stated | not extracted yet |
| Marini 1993 Serine for glycine substitutions in type I collagen in two cases of type IV osteogenesis imperfecta (OI). Additional evidence for a… DOI:10.1016/s0021-9258(18)53826-6 | 1993 | this review only | not stated | not extracted yet |
| Maroteaux 1988 Clinical and Genetical Heterogeneity of Osteogenesis Imperfecta DOI:10.1111/j.1749-6632.1988.tb55312.x | 1988 | this review only | Hydroxylysine (HYL) percentage in collagen-I; Hydroxyproline (HYP) percentage in collagen-I; Glycosylation ratio (diglycosylated/monoglycosylated hydroxylysine, GGHYL/GHYL) in collagen-I | not extracted yet |
| Meigel 1975 Disturbance in the Regulation of the Type of Collagen Synthesized in a Form of Osteogenesis Imperfecta DOI:10.1111/j.1432-1033.1975.tb02429.x | 1975 | this review only | Hydroxyproline (HYP) percentage in collagen-I | not extracted yet |
| Nicholls 1991 Substitution of cysteine for glycine at residue 415 of one allele of the alpha 1(I) chain of type I procollagen in type III/IV… DOI:10.1136/jmg.28.11.757 | 1991 | this review only | not stated | not extracted yet |
| Pace 2001 Deletions and duplications of Gly-Xaa-Yaa triplet repeats in the triple helical domains of type I collagen chains disrupt helix formation… DOI:10.1002/humu.1193 | 2001 | this review only | not stated | not extracted yet |
| Pace 2001 Disruption of one intra-chain disulphide bond in the carboxyl-terminal propeptide of the proα1(I) chain of type I procollagen permits slow… DOI:10.1136/jmg.38.7.443 | 2001 | this review only | not stated | not extracted yet |
| Pace 2002 A single amino acid substitution (D1441Y) in the carboxyl-terminal propeptide of the proα1(I) chain of type I collagen results in a lethal… DOI:10.1136/jmg.39.1.23 | 2002 | this review only | not stated | not extracted yet |
| Rao 1989 Decreased Thermal Denaturation Temperature of Osteogenesis Imperfecta Mutant Collagen is Independent of Post-translational… DOI:10.1016/s0021-9258(18)94257-2 | 1989 | this review only | Hydroxylysine (HYL) percentage in collagen-I; Hydroxyproline (HYP) percentage in collagen-I | not extracted yet |
| Sarafova 1998 Three novel type I collagen mutations in osteogenesis imperfecta type IV probands are associated with discrepancies between… DOI:10.1002/(sici)1098-1004(1998)11:5<395::aid-humu7>3.0.co;2-4 | 1998 | this review only | not stated | not extracted yet |
| Sippola 1984 A heterozygous defect for structurally altered pro-alpha 2 chain of type I procollagen in a mild variant of osteogenesis imperfecta. The… DOI:10.1016/s0021-9258(18)89861-1 | 1984 | this review only | not stated | not extracted yet |
| Starman 1989 Osteogenesis imperfecta. The position of substitution for glycine by cysteine in the triple helical domain of the pro alpha 1(I) chains of… DOI:10.1172/jci114286 | 1989 | this review only | not stated | not extracted yet |
| Steinmann 1984 Clinical variability of osteogenesis imperfecta reflecting molecular heterogeneity: cysteine substitutions in the alpha 1(I) collagen… DOI:10.1016/s0021-9258(19)84475-7 | 1986 | this review only | Hydroxylysine (HYL) percentage in collagen-I; Hydroxyproline (HYP) percentage in collagen-I; Glycosylation ratio (diglycosylated/monoglycosylated hydroxylysine, GGHYL/GHYL) in collagen-I | not extracted yet |
| Stoss 1986 Heterogeneity of osteogenesis imperfecta. Biochemical and morphological findings in a case of type III according to Sillence DOI:10.1007/bf00441849 | 1986 | this review only | Hydroxylysine (HYL) percentage in collagen-I; Hydroxyproline (HYP) percentage in collagen-I; Ratio of hydroxylysine to hydroxyproline (HYL/HYP) in collagen-I | not extracted yet |
| Superti-Furga 1988 Delayed Triple‐Helix Formation of Abnormal Type I Collagen Is Corrected by Reduced Temperature DOI:10.1111/j.1749-6632.1988.tb55319.x | 1988 | this review only | not stated | not extracted yet |
| Taga 2013 Site-specific Quantitative Analysis of Overglycosylation of Collagen in Osteogenesis Imperfecta Using Hydrazide Chemistry and SILAC DOI:10.1021/pr400079d | 2013 | this review only | not stated | not extracted yet |
| Tajima 1994 Production of Overmodified Type I Procollagen in a Case of Osteogenesis Imperfecta DOI:10.1111/j.1346-8138.1994.tb01726.x | 1994 | this review only | Hydroxylysine (HYL) percentage in collagen-I; Hydroxyproline (HYP) percentage in collagen-I; Glycosylation ratio (diglycosylated/monoglycosylated hydroxylysine, GGHYL/GHYL) in collagen-I | not extracted yet |
| Takagi 1980 Dentinogenesis imperfecta: evidence of qualitative alteration in the organic dentin matrix DOI:10.1111/j.1600-0714.1980.tb00378.x | 1980 | this review only | Hydroxylysine (HYL) percentage in collagen-I; Hydroxyproline (HYP) percentage in collagen-I | not extracted yet |
| Takeyari 2020 4-Phenylbutyric acid enhances the mineralization of osteogenesis imperfecta iPSC-derived osteoblasts DOI:10.1074/jbc.ra120.014709 | 2021 | this review only | not stated | not extracted yet |
| Tenni 1988 Type I procollagen in the severe non-lethal form of osteogenesis imperfecta DOI:10.1007/bf00366245 | 1988 | this review only | Hydroxylysine (HYL) percentage in collagen-I; Hydroxyproline (HYP) percentage in collagen-I; Glycosylation ratio (diglycosylated/monoglycosylated hydroxylysine, GGHYL/GHYL) in collagen-I | not extracted yet |
| Tenni 1988 Severe Nonlethal Osteogenesis Imperfecta: Biochemical Heterogeneity<sup>a</sup> DOI:10.1111/j.1749-6632.1988.tb55317.x | 1988 | this review only | not stated | not extracted yet |
| Tenni 1991 Phenotypic variability and abnormal type I collagen unstable at body temperature in a family with mild dominant osteogenesis imperfecta DOI:10.1007/bf01800591 | 1990 | this review only | not stated | not extracted yet |
| Trelstad 1977 matched by author and year (probable) | NR | this review only | Hydroxylysine (HYL) percentage in collagen-I | not extracted yet |
| Valli 1990 Moderately Severe Osteogenesis Imperfecta: Biochemical Studies Showing Variable Defect Localization in the Triple-Helical Domain of Type I… DOI:10.1016/s0934-8832(11)80169-1 | 1990 | this review only | not stated | not extracted yet |
| Valli 1993 Osteogenesis imprefecta and type‐I collagen mutations DOI:10.1111/j.1432-1033.1993.tb17565.x | 1993 | this review only | not stated | not extracted yet |
| Wallis 1990 Substitution of arginine for glycine at position 847 in the triple-helical domain of the alpha 1 (I) chain of type I collagen produces… DOI:10.1016/s0021-9258(17)44798-3 | 1990 | this review only | not stated | not extracted yet |
| Wallis 1992 A tripeptide deletion in the triple-helical domain of the pro alpha 1(I) chain of type I procollagen in a patient with lethal osteogenesis… DOI:10.1016/s0021-9258(19)74072-1 | 1992 | this review only | not stated | not extracted yet |
| Wenstrup 1986 Osteogenesis imperfecta type IV: evidence of abnormal triple helical structure of type I collagen DOI:10.1007/bf00278784 | 1986 | this review only | not stated | not extracted yet |
| Wenstrup 1986 Osteogenesis imperfecta type IV. Biochemical confirmation of genetic linkage to the pro alpha 2(I) gene of type I collagen. DOI:10.1172/jci112735 | 1986 | this review only | not stated | not extracted yet |
| Wenstrup 1988 Arginine for glycine substitution in the triple-helical domain of the products of one alpha 2(I) collagen allele (COL1A2) produces the… DOI:10.1016/s0021-9258(18)68560-6 | 1988 | this review only | not stated | not extracted yet |
| Willing 1988 Heterozygosity for a large deletion in the alpha 2(I) collagen gene has a dramatic effect on type I collagen secretion and produces… DOI:10.1016/s0021-9258(18)68491-1 | 1988 | this review only | not stated | not extracted yet |
Review question
| Element | Planned (methods) | Found (results) |
|---|---|---|
| Population | Patients with osteogenesis imperfecta due to collagen-I mutations; animal studies and non collagen-I OI types excluded | OI patients (269 patients in 70 studies; 150 in HYL, 141 in HYP and 17 in GLY meta-analyses) |
| Intervention | Collagen-I from OI patients (bone, fibroblast, dentine) assessed for post-translational modifications | OI collagen-I from bone, fibroblast or dentine (n=25 meta-analysis studies) |
| Comparison | Healthy control collagen-I | Internal healthy controls |
| Outcomes | Hydroxylysine (HYL), hydroxyproline (HYP), glycosylation (GLY); association with OI severity | HYL (20 datasets), HYP (17), HYL/HYP ratio (10), GLY ratio (5); 36 qualitative studies all reported overmodified collagen-I |
| Study designs | Experimental studies (case reports, case series, cohort studies) assessing collagen-I post-translational modifications | 36 qualitative, 9 quantitative not pooled, 25 quantitative pooled (13 case reports, 4 case series, 8 cohort studies) |
| Timing | Not specified | Not specified |