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Osteogenesis Imperfecta Type IV

Disease Pathophysiology Research Report

2026-02-04
Falcon MONDO:0008148 Model: Edison Scientific Literature 28 citations

Disease Pathophysiology Research Report

Target Disease - Disease Name: Osteogenesis Imperfecta Type IV (OI type IV) - MONDO ID: Not definitively identified in the evidence retrieved here; OI is a Mendelian collagen type I disorder predominantly due to COL1A1/COL1A2 variants (classification updates noted below). (sillence2024adyadicnosology pages 8-9) - Category: Mendelian

Plan (concise) - Define scope and taxonomy (OI type IV within Sillence/ISDS dyadic nosology). (sillence2024adyadicnosology pages 8-9) - Synthesize core molecular/cellular pathophysiology and dysregulated pathways. (claeys2021collagentransportand pages 1-2, yu2023pathogenicmechanismsof pages 1-2) - Enumerate key molecular players (genes/proteins, cell types, tissues; chemicals relevant to management). (claeys2021collagentransportand pages 1-2, kresnadi2024theroleof pages 2-5, sillence2024adyadicnosology pages 8-9) - Map biological processes and cellular components (GO-aligned). (claeys2021collagentransportand pages 1-2, yu2023pathogenicmechanismsof pages 1-2) - Outline disease progression from mutation to phenotype with representative HPO-style phenotypes. (yu2023pathogenicmechanismsof pages 1-2, khan2024beyondbrittlebones pages 2-3) - Summarize 2023–2024 developments (nosology updates, management evidence, dentition data). (sillence2024adyadicnosology pages 8-9, kresnadi2024theroleof pages 2-5, ventura2024dentalabnormalitiesin pages 1-2) - Assemble evidence with URLs and dates.

Pathophysiology description - Core concept: OI type IV sits in the classical Sillence I–IV spectrum, typically caused by autosomal dominant COL1A1 or COL1A2 variants that either reduce type I collagen quantity (haploinsufficiency) or alter collagen structure (dominant-negative glycine substitutions in the Gly-X-Y repeats), impairing extracellular matrix assembly and bone material quality. “Qualitative and quantitative defects in type I collagen polypeptides were postulated to account for the genetic heterogeneity in OI,” and type 4 historically reflects a moderate severity phenotype in this spectrum. (sillence2024adyadicnosology pages 8-9) - Molecular mechanisms: Mechanistic classes relevant to type IV include defects in type I collagen synthesis, post-translational modification, folding, and cross-linking; bone mineralization defects; and osteoblast differentiation/function abnormalities. The review explicitly proposes mechanistic classification across these axes for OI, with COL1A1/COL1A2 in the collagen-defect class underpinning classical types including type IV. (yu2023pathogenicmechanismsof pages 1-2) - Cellular and pathway dysregulation: The collagen I lifecycle spans ER synthesis and folding, chaperone-assisted post-translational modification, ER–Golgi transport, extracellular processing, and fibrillogenesis. Disruptions at any stage weaken the ECM. Emerging contributors include retrograde ER–Golgi transport components and WNT signaling, with osteoblast and osteocyte signaling networks broadly altered. (claeys2021collagentransportand pages 1-2) - Bone remodeling signaling: Recent reviews emphasize TGF-β/SMAD signaling in OI pathogenesis and its interplay with osteoblast/osteoclast balance; WNT pathway perturbations (e.g., sclerostin/DKK1) modulate osteogenesis and are therapeutic targets. (yu2023pathogenicmechanismsof pages 1-2, sillence2024adyadicnosology pages 8-9)

Key molecular players and affected biology - Genes/Proteins (HGNC): - COL1A1 (HGNC:2197) and COL1A2 (HGNC:2198) encode the type I collagen chains; missense glycine substitutions often cause structural defects (dominant-negative), while nonsense/frameshift/splice variants usually cause haploinsufficiency. Type IV commonly arises from these mechanisms. (claeys2021collagentransportand pages 1-2, yu2023pathogenicmechanismsof pages 1-2, sillence2024adyadicnosology pages 8-9) - Locus heterogeneity and modifiers: ISDS/2024 nosology recognizes >24 OI/bone fragility entities, with additional AD/AR/X-linked loci and reports of digenic contributions (e.g., variants affecting WNT signaling), which may influence expressivity in “type 4-like” phenotypes. (sillence2024adyadicnosology pages 8-9) - Variant classes typical for type IV and consequences: - Glycine substitutions in the collagen triple helix (qualitative defects) lead to delayed triple-helix folding, overmodification, ER stress, abnormal fibrillogenesis, and brittle matrix—consistent with moderate severity type IV phenotypes. (claeys2021collagentransportand pages 1-2, yu2023pathogenicmechanismsof pages 1-2) - Quantitative defects (COL1A1 LOF) more often produce type I; however, phenotypic overlap between types I and IV is common, and intrafamilial variability is recognized. (sillence2024adyadicnosology pages 8-9) - Cell types (CL): Osteoblasts (matrix production), osteocytes (mechanosensing; transcriptome dysregulation), and osteoclasts (resorption). In dentition, odontoblasts are affected, explaining DI. (claeys2021collagentransportand pages 1-2, yu2023pathogenicmechanismsof pages 1-2, ventura2024dentalabnormalitiesin pages 1-2) - Tissues/organs (UBERON): Bone element (skeleton) is primary; teeth/dentin and periodontal ligament, sclera, and auditory structures (cochlea/ossicles) can be involved, reflecting type I collagen distribution. (claeys2021collagentransportand pages 1-2, khan2024beyondbrittlebones pages 2-3, ventura2024dentalabnormalitiesin pages 1-2) - Chemical entities (CHEBI) relevant to management: Bisphosphonates (e.g., pamidronate, zoledronic acid) and anabolic teriparatide are commonly discussed in OI care and trials. (kresnadi2024theroleof pages 2-5, hasegawa2025osteogenesisimperfectapathogenesis pages 1-2)

Biological processes (for GO annotation) and cellular components - Processes: extracellular matrix organization; collagen fibril organization; bone mineralization; TGF-β signaling pathway; WNT signaling pathway; osteoblast differentiation and osteoclast regulation. These processes capture the major axes of dysregulation in OI type IV. (claeys2021collagentransportand pages 1-2, yu2023pathogenicmechanismsof pages 1-2, sillence2024adyadicnosology pages 8-9) - Cellular components: endoplasmic reticulum (collagen synthesis/folding), Golgi apparatus (procollagen processing/trafficking), and extracellular matrix (mature fibrils). (claeys2021collagentransportand pages 1-2, yu2023pathogenicmechanismsof pages 1-2)

Ontology-mapped summary (embed) | Category | Entity | Ontology ID | Role / Relevance | Representative sources | |---|---|---:|---|---| | Gene / Protein | COL1A1 (pro-alpha1(I)) | HGNC:2197 | Encodes type I collagen α1 chain; dominant glycine substitutions or haploinsufficiency underlie many OI type IV cases and disrupt triple-helix formation. | (claeys2021collagentransportand pages 1-2, yu2023pathogenicmechanismsof pages 1-2, sillence2024adyadicnosology pages 8-9) | | Gene / Protein | COL1A2 (pro-alpha2(I)) | HGNC:2198 | Encodes type I collagen α2 chain; variants (glycine substitutions) frequently cause structural collagen defects and associate with DI in some cases. | (claeys2021collagentransportand pages 1-2, yu2023pathogenicmechanismsof pages 1-2, sillence2024adyadicnosology pages 8-9, ventura2024dentalabnormalitiesin pages 1-2) | | Biological Process | Extracellular matrix organization | GO:0030198 | Disrupted ECM assembly and collagen deposition reduce bone matrix integrity and increase fragility. | (claeys2021collagentransportand pages 1-2, yu2023pathogenicmechanismsof pages 1-2) | | Biological Process | Collagen fibril organization | GO:0030199 | Abnormal fibrillogenesis from mutant collagen (glycine substitutions) alters fibril structure and mechanical properties. | (claeys2021collagentransportand pages 1-2, yu2023pathogenicmechanismsof pages 1-2, sillence2024adyadicnosology pages 8-9) | | Biological Process | Bone mineralization | GO:0030282 | Impaired mineral deposition and matrix mineralization contribute to low BMD and fractures in OI. | (yu2023pathogenicmechanismsof pages 1-2, ventura2024dentalabnormalitiesin pages 1-2) | | Biological Process | TGF‑beta signaling pathway | GO:0007179 | Upregulated TGF‑β signaling implicated in altered bone turnover, osteoblast/osteoclast imbalance and skeletal deformities. | (yu2023pathogenicmechanismsof pages 1-2, sillence2024adyadicnosology pages 8-9, kresnadi2024theroleof pages 2-5) | | Biological Process | Wnt signaling pathway | GO:0016055 | Regulates osteoblast activity; pathway targeted by sclerostin/DKK1 modulators under investigation for OI. | (claeys2021collagentransportand pages 1-2, sillence2024adyadicnosology pages 8-9, dinulescu2024newperspectivesof pages 1-2) | | Cellular Component | Endoplasmic reticulum | GO:0005783 | Site of collagen chain synthesis and folding; mutant collagen causes ER stress and chaperone pathway involvement. | (claeys2021collagentransportand pages 1-2, yu2023pathogenicmechanismsof pages 1-2) | | Cellular Component | Golgi apparatus | GO:0005794 | Procollagen processing and trafficking; transport defects (ER‑Golgi) can contribute to OI pathogenesis. | (claeys2021collagentransportand pages 1-2) | | Cellular Component | Extracellular matrix | GO:0031012 | Location of mature type I collagen fibrils; structural defects here directly weaken bone and dentin. | (claeys2021collagentransportand pages 1-2, yu2023pathogenicmechanismsof pages 1-2) | | Cell Type | Osteoblast | CL:0000062 | Collagen‑producing bone‑forming cells; impaired secretion/function leads to defective matrix formation. | (claeys2021collagentransportand pages 1-2, yu2023pathogenicmechanismsof pages 1-2) | | Cell Type | Osteocyte | CL:0000138 | Long‑lived mechanosensors; transcriptome dysregulation in OI models indicates altered signaling and bone homeostasis. | (claeys2021collagentransportand pages 2-4, yu2023pathogenicmechanismsof pages 1-2) | | Cell Type | Osteoclast | CL:0000092 | Bone‑resorbing cells; activity modulated by RANK/RANKL and TGF‑β—contributes to turnover imbalance in OI. | (yu2023pathogenicmechanismsof pages 1-2, kresnadi2024theroleof pages 2-5) | | Cell Type | Odontoblast | CL:0000067 | Dentin‑forming cells affected by collagen I defects, producing dentinogenesis imperfecta (DI) phenotypes. | (ventura2024dentalabnormalitiesin pages 1-2) | | Anatomical Location | Bone element | UBERON:0001474 | Primary organ system affected: low bone mass, fractures, deformity. | (claeys2021collagentransportand pages 1-2, sillence2024adyadicnosology pages 8-9) | | Anatomical Location | Dentin | UBERON:0001752 | Tissue with high collagen I content; explains DI prevalence in OI (approx. 20–48% reported). | (ventura2024dentalabnormalitiesin pages 1-2) | | Anatomical Location | Sclera | UBERON:0001772 | Altered collagen in sclera produces blue/gray sclerae in many OI patients (variable by subtype). | (khan2024beyondbrittlebones pages 2-3, sillence2024adyadicnosology pages 8-9) | | Anatomical Location | Cochlea | UBERON:0002247 | Auditory structures can be affected leading to hearing impairment in OI. | (khan2024beyondbrittlebones pages 2-3) | | Chemical Entity | Zoledronic acid | CHEBI:101277 | Intravenous bisphosphonate antiresorptive used in OI management to increase BMD and reduce bone pain/fractures. | (hasegawa2025osteogenesisimperfectapathogenesis pages 1-2, kresnadi2024theroleof pages 2-5) | | Chemical Entity | Pamidronate | CHEBI:8069 | Pediatric bisphosphonate commonly used off‑label to treat children with OI. | (hasegawa2025osteogenesisimperfectapathogenesis pages 1-2, kresnadi2024theroleof pages 2-5) | | Chemical Entity | Teriparatide | CHEBI:38763 | PTH(1‑34) anabolic agent under investigation (adult OI trials) as a bone‑forming therapy. | (dinulescu2024newperspectivesof pages 1-2, kresnadi2024theroleof pages 2-5) |

Table: Compact ontology‑mapped summary of key genes, processes, components, cell types, anatomical sites and management chemicals relevant to Osteogenesis Imperfecta Type IV, with representative supporting sources (pqac IDs). This table is useful for integrating mechanistic annotations into knowledge bases and for rapid literature-linked reference.

Disease progression and sequence of events - Initiating trigger: Pathogenic variants in COL1A1 or COL1A2 (often glycine substitutions) impair triple-helix formation and/or reduce collagen I quantity. (claeys2021collagentransportand pages 1-2, yu2023pathogenicmechanismsof pages 1-2, sillence2024adyadicnosology pages 8-9) - Intracellular consequences: Delayed folding and overmodification of procollagen chains in the ER, increased chaperone engagement, ER stress; impaired ER–Golgi trafficking; abnormal secretion. (claeys2021collagentransportand pages 1-2, yu2023pathogenicmechanismsof pages 1-2) - Extracellular consequences: Disordered fibrillogenesis and aberrant collagen cross-linking; altered mineralization; compromised microarchitecture. (claeys2021collagentransportand pages 1-2, yu2023pathogenicmechanismsof pages 1-2) - Tissue-level remodeling: Dysregulated TGF-β and WNT signaling in bone remodeling skews osteoblast/osteoclast coupling, compounding fragility and deformity. (yu2023pathogenicmechanismsof pages 1-2, sillence2024adyadicnosology pages 8-9) - Clinical manifestations: Moderately severe bone fragility with recurrent long-bone fractures, variable deformities, short stature, scoliosis/kyphosis, and variable extraskeletal features (teeth, sclerae, hearing). Type IV often has normal or gray sclerae and can present with DI; phenotypic overlap with types I/III exists and intrafamilial variability is common. (sillence2024adyadicnosology pages 8-9, khan2024beyondbrittlebones pages 2-3, ventura2024dentalabnormalitiesin pages 1-2)

Phenotypic manifestations (HPO-style, representative) - Fragile bones/recurrent fractures; skeletal deformities (e.g., scoliosis/kyphosis); short stature; dentinogenesis imperfecta type I (variable, 20–48% across OI collectively; more frequent in severe skeletal types including III/IV); hearing impairment in some. “Those with a more severe skeletal phenotype (OI type III/IV) exhibited more dental abnormalities than those with a milder skeletal phenotype (OI type I).” (ventura2024dentalabnormalitiesin pages 1-2)

Recent developments and latest research (prioritizing 2023–2024) - Nosology update (ISDS-informed, 2024): The “dyadic nosology” links genomic co-descriptors to Sillence phenotypes, acknowledging >24 loci and significant heterogeneity and overlap; it emphasizes integrating clinical severity with genotype for entities such as “type 4” and warns about historical misinterpretations of Sillence categories. (sillence2024adyadicnosology pages 8-9) - Management in children (2024 expert review): Bisphosphonates remain widely used off-label in pediatric OI, but meta-analyses show equivocal anti-fracture efficacy; standardized dosing and long-term outcome data are needed. Targeted antibody therapies developed for osteoporosis (e.g., anti-sclerostin, anti-RANKL) are under investigation in OI and may gain approvals in the coming years. (stasek2025osteogenesisimperfectashifting pages 1-2) - Adult/pediatric management overview (2024 review): Denosumab and bisphosphonates modulate bone turnover; literature suggests improvements in BMD and symptoms, but long-term safety/efficacy and fracture outcomes require further study; optimization of dosing/timing remains under evaluation. (kresnadi2024theroleof pages 2-5) - Mechanism-focused classification (2023): A framework aligning genetic defects to pathogenic mechanisms—collagen defects, mineralization disorders, and osteoblast differentiation/function—provides a scientific basis to stratify OI, including classical type IV within collagen-defect mechanisms. (yu2023pathogenicmechanismsof pages 1-2) - Dental phenotype epidemiology (2024 systematic review): Among OI patients, DI prevalence ~20–48%; occlusal anomalies and missing/unerupted teeth are common, especially in type III/IV; OI type V generally lacks DI. This supports dental surveillance and genotype-informed risk stratification. (ventura2024dentalabnormalitiesin pages 1-2)

Expert opinions and authoritative analyses - Sillence (2024) emphasizes the utility of dyadic nosology that pairs phenotype labels (e.g., type IV) with genomic co-descriptors, reflects extensive allelic heterogeneity at COL1A1/COL1A2 and beyond, and notes variable expressivity and intrafamilial variability in type IV families. (sillence2024adyadicnosology pages 8-9) - Pediatric care perspective (2025 review with 2024 evidence): The field is shifting toward targeted biologics while recognizing that bisphosphonates remain common practice and that fracture-prevention evidence must be strengthened; TGF-β and WNT pathways are repeatedly highlighted as rational targets. (stasek2025osteogenesisimperfectashifting pages 1-2)

Relevant statistics and data - Genetic attribution: ~85–90% of OI cases from COL1A1/COL1A2 variants; type IV is commonly linked to qualitative glycine substitutions but overlaps with other classes. (claeys2021collagentransportand pages 1-2, yu2023pathogenicmechanismsof pages 1-2, sillence2024adyadicnosology pages 8-9) - Dental abnormalities: DI in OI overall ~20–48%; occlusion classes vary widely, with Class III malocclusion unusually frequent; more anomalies in type III/IV than type I. (ventura2024dentalabnormalitiesin pages 1-2)

Direct quotes (selected) - “Qualitative and quantitative defects in type I collagen polypeptides were postulated to account for the genetic heterogeneity in OI…” (Sillence 2024). (sillence2024adyadicnosology pages 8-9) - “We summarize… molecular pathogenic mechanisms of OI from the perspectives of type I collagen defects… bone mineralization disorders, osteoblast differentiation and functional defects.” (Yu 2023). (yu2023pathogenicmechanismsof pages 1-2) - “The included studies confirmed that dental abnormalities are prevalent in OI, with DI prevalence ranging from approximately 20 to 48%… those with a more severe skeletal phenotype (OI type III/IV) exhibited more dental abnormalities…” (Ventura 2024). (ventura2024dentalabnormalitiesin pages 1-2) - “There are no licensed treatments for children with osteogenesis imperfecta… Meta-analyses suggest that anti-fracture efficacy… is equivocal. New therapies are undergoing clinical trials…” (Arundel & Bishop 2024). (stasek2025osteogenesisimperfectashifting pages 1-2)

Applications and real-world implementations - Off-label antiresorptives (pamidronate, zoledronic acid) widely used in pediatric OI care; systematic expert reviews call for harmonized dosing and robust long-term outcomes data. (stasek2025osteogenesisimperfectashifting pages 1-2, hasegawa2025osteogenesisimperfectapathogenesis pages 1-2) - Adult programs increasingly evaluate anabolic/antiresorptive sequences (e.g., teriparatide followed by antiresorptives in broader OI literature), though fracture-reduction evidence remains limited and is an active trial focus (outside the specific sources cited here). (kresnadi2024theroleof pages 2-5) - Multidisciplinary monitoring for dental abnormalities is warranted given high prevalence of DI and malocclusion, particularly in type III/IV cohorts. (ventura2024dentalabnormalitiesin pages 1-2)

Gene/protein annotations with ontology terms - COL1A1 (HGNC:2197); COL1A2 (HGNC:2198). Processes: extracellular matrix organization (GO:0030198); collagen fibril organization (GO:0030199); bone mineralization (GO:0030282); TGF-β signaling pathway (GO:0007179); WNT signaling pathway (GO:0016055). Components: endoplasmic reticulum (GO:0005783); Golgi apparatus (GO:0005794); extracellular matrix (GO:0031012). (claeys2021collagentransportand pages 1-2, yu2023pathogenicmechanismsof pages 1-2, sillence2024adyadicnosology pages 8-9)

Phenotype associations (HPO terms, descriptive) - Recurrent fractures; skeletal deformities including scoliosis/kyphosis; short stature; dentinogenesis imperfecta type I; variable hearing loss; normal/gray sclerae in many type IV patients. (sillence2024adyadicnosology pages 8-9, khan2024beyondbrittlebones pages 2-3, ventura2024dentalabnormalitiesin pages 1-2)

Cell type involvement (CL terms) - Osteoblasts (CL:0000062), osteocytes (CL:0000138), osteoclasts (CL:0000092), odontoblasts (CL:0000067). (claeys2021collagentransportand pages 1-2, yu2023pathogenicmechanismsof pages 1-2, ventura2024dentalabnormalitiesin pages 1-2)

Anatomical locations (UBERON terms) - Bone element (UBERON:0001474); dentin (UBERON:0001752); sclera (UBERON:0001772); cochlea (UBERON:0002247). (claeys2021collagentransportand pages 1-2, khan2024beyondbrittlebones pages 2-3, ventura2024dentalabnormalitiesin pages 1-2)

Chemical entities (CHEBI terms) - Zoledronic acid (CHEBI:101277); Pamidronate (CHEBI:8069); Teriparatide (CHEBI:38763). (kresnadi2024theroleof pages 2-5, hasegawa2025osteogenesisimperfectapathogenesis pages 1-2)

Limitations of the current evidence set - While multiple 2023–2024 sources were integrated (nosology, dental epidemiology, management reviews, mechanism classification), some highly relevant 2024 bench/clinical studies on TGF-β modulation (e.g., losartan models) and WNT modulators (e.g., sclerostin/DKK1-targeted agents) were identified in searches but not retrievable as citable evidence items in this session; claims regarding these specific agents are therefore framed at the pathway level using authoritative reviews. (yu2023pathogenicmechanismsof pages 1-2, sillence2024adyadicnosology pages 8-9)

Evidence items with PMIDs/DOIs, URLs, publication dates - Sillence DO. A dyadic nosology for Osteogenesis Imperfecta and Bone Fragility Syndromes 2024. Calcif Tissue Int. 2024 Jun;115:873–890. doi:10.1007/s00223-024-01248-7. URL: https://doi.org/10.1007/s00223-024-01248-7 (sillence2024adyadicnosology pages 8-9) - Yu H, et al. Pathogenic mechanisms of osteogenesis imperfecta, evidence for classification. Orphanet J Rare Dis. 2023 Aug. doi:10.1186/s13023-023-02849-5. URL: https://doi.org/10.1186/s13023-023-02849-5 (yu2023pathogenicmechanismsof pages 1-2) - Claeys L, et al. Collagen transport and related pathways in Osteogenesis Imperfecta. Hum Genet. 2021 Jun;140:1121–1141. doi:10.1007/s00439-021-02302-2. URL: https://doi.org/10.1007/s00439-021-02302-2 (claeys2021collagentransportand pages 1-2) - Ventura L, et al. Dental Abnormalities in Osteogenesis Imperfecta: A Systematic Review. Calcif Tissue Int. 2024 Sep;115:461–479. doi:10.1007/s00223-024-01293-2. URL: https://doi.org/10.1007/s00223-024-01293-2 (ventura2024dentalabnormalitiesin pages 1-2) - Arundel P, Bishop N. Medical Management for Fracture Prevention in Children with OI. Calcif Tissue Int. 2024 Mar;115:812–827. doi:10.1007/s00223-024-01202-7. URL: https://doi.org/10.1007/s00223-024-01202-7 (stasek2025osteogenesisimperfectashifting pages 1-2) - Kresnadi A, et al. The Role of Denosumab and Bisphosphonate in OI: A Literature Review. Salud, Ciencia y Tecnología. 2024 Apr;4:894. doi:10.56294/saludcyt2024894. URL: https://doi.org/10.56294/saludcyt2024894 (kresnadi2024theroleof pages 2-5) - Hasegawa K. Osteogenesis imperfecta: pathogenesis, classification, and treatment. Clin Pediatr Endocrinol. 2025 Jan;34:152–161. doi:10.1297/cpe.2025-0009. URL: https://doi.org/10.1297/cpe.2025-0009 (hasegawa2025osteogenesisimperfectapathogenesis pages 1-2) - Khan H, et al. Beyond brittle bones: Genetic mechanisms underlying OI. World Acad Sci J. 2024 Oct. doi:10.3892/wasj.2024.284. URL: https://doi.org/10.3892/wasj.2024.284 (khan2024beyondbrittlebones pages 2-3) - Dinulescu A, et al. New Perspectives of Therapies in OI—A Literature Review. J Clin Med. 2024 Feb;13:1065. doi:10.3390/jcm13041065. URL: https://doi.org/10.3390/jcm13041065 (dinulescu2024newperspectivesof pages 1-2)

Overall synthesis - OI type IV reflects a moderate-severity collagen I matrix disorder centered on COL1A1/COL1A2 variants that disrupt collagen biosynthesis and extracellular assembly, with secondary dysregulation of TGF-β and WNT pathways affecting bone remodeling. Clinically, it features recurrent fractures, deformity, short stature, and variable DI/hearing/scleral involvement, with substantial overlap across classical Sillence types. 2023–2024 updates emphasize nosology integration of genotype and phenotype, caution about equivocal anti-fracture evidence for pediatric bisphosphonates, and growing interest in targeted pathway therapies; robust long-term fracture outcomes and standardized approaches remain priorities. (sillence2024adyadicnosology pages 8-9, yu2023pathogenicmechanismsof pages 1-2, stasek2025osteogenesisimperfectashifting pages 1-2, kresnadi2024theroleof pages 2-5, ventura2024dentalabnormalitiesin pages 1-2)

References

  1. (sillence2024adyadicnosology pages 8-9): David Owen Sillence. A dyadic nosology for osteogenesis imperfecta and bone fragility syndromes 2024. Calcified Tissue International, 115:873-890, Jun 2024. URL: https://doi.org/10.1007/s00223-024-01248-7, doi:10.1007/s00223-024-01248-7. This article has 29 citations and is from a peer-reviewed journal.

  2. (claeys2021collagentransportand pages 1-2): Lauria Claeys, Silvia Storoni, Marelise Eekhoff, Mariet Elting, Lisanne Wisse, Gerard Pals, Nathalie Bravenboer, Alessandra Maugeri, and Dimitra Micha. Collagen transport and related pathways in osteogenesis imperfecta. Human Genetics, 140:1121-1141, Jun 2021. URL: https://doi.org/10.1007/s00439-021-02302-2, doi:10.1007/s00439-021-02302-2. This article has 108 citations and is from a peer-reviewed journal.

  3. (yu2023pathogenicmechanismsof pages 1-2): Hongjie Yu, Changrong Li, Huixiao Wu, Weibo Xia, Yanzhou Wang, Jiajun Zhao, and Chao Xu. Pathogenic mechanisms of osteogenesis imperfecta, evidence for classification. Orphanet Journal of Rare Diseases, Aug 2023. URL: https://doi.org/10.1186/s13023-023-02849-5, doi:10.1186/s13023-023-02849-5. This article has 31 citations and is from a peer-reviewed journal.

  4. (kresnadi2024theroleof pages 2-5): Agus Kresnadi, Tri Wahyu Martanto, Arif Zulkarnain, and Hizbillah Yazid. The role of denosumab and bisphosphonate in osteogenesis imperfecta: a literature review. Salud, Ciencia y Tecnología, 4:894, Apr 2024. URL: https://doi.org/10.56294/saludcyt2024894, doi:10.56294/saludcyt2024894. This article has 1 citations.

  5. (khan2024beyondbrittlebones pages 2-3): Hammal Khan, Zaheer Ahmed, and Muhammad Umair. Beyond brittle bones: genetic mechanisms underlying osteogenesis imperfecta (review). World Academy of Sciences Journal, Oct 2024. URL: https://doi.org/10.3892/wasj.2024.284, doi:10.3892/wasj.2024.284. This article has 1 citations.

  6. (ventura2024dentalabnormalitiesin pages 1-2): Laura Ventura, Sara J. E. Verdonk, Lidiia Zhytnik, Angela Ridwan-Pramana, Marjolijn Gilijamse, Willem H. Schreuder, Kirsten A. van Gelderen-Ziesemer, Ton Schoenmaker, Dimitra Micha, and Elisabeth M. W. Eekhoff. Dental abnormalities in osteogenesis imperfecta: a systematic review. Calcified Tissue International, 115:461-479, Sep 2024. URL: https://doi.org/10.1007/s00223-024-01293-2, doi:10.1007/s00223-024-01293-2. This article has 14 citations and is from a peer-reviewed journal.

  7. (hasegawa2025osteogenesisimperfectapathogenesis pages 1-2): Kosei Hasegawa. Osteogenesis imperfecta: pathogenesis, classification, and treatment. Clinical Pediatric Endocrinology, 34:152-161, Jan 2025. URL: https://doi.org/10.1297/cpe.2025-0009, doi:10.1297/cpe.2025-0009. This article has 1 citations and is from a peer-reviewed journal.

  8. (dinulescu2024newperspectivesof pages 1-2): Alexandru Dinulescu, Alexandru-Sorin Păsărică, Mădălina Carp, Andrei Dușcă, Irina Dijmărescu, Mirela Luminița Pavelescu, Daniela Păcurar, and Alexandru Ulici. New perspectives of therapies in osteogenesis imperfecta—a literature review. Journal of Clinical Medicine, 13:1065, Feb 2024. URL: https://doi.org/10.3390/jcm13041065, doi:10.3390/jcm13041065. This article has 23 citations and is from a poor quality or predatory journal.

  9. (claeys2021collagentransportand pages 2-4): Lauria Claeys, Silvia Storoni, Marelise Eekhoff, Mariet Elting, Lisanne Wisse, Gerard Pals, Nathalie Bravenboer, Alessandra Maugeri, and Dimitra Micha. Collagen transport and related pathways in osteogenesis imperfecta. Human Genetics, 140:1121-1141, Jun 2021. URL: https://doi.org/10.1007/s00439-021-02302-2, doi:10.1007/s00439-021-02302-2. This article has 108 citations and is from a peer-reviewed journal.

  10. (stasek2025osteogenesisimperfectashifting pages 1-2): Stefanie Stasek, Frank Zaucke, Heike Hoyer-Kuhn, Julia Etich, Susanna Reincke, Isabell Arndt, Mirko Rehberg, and Oliver Semler. Osteogenesis imperfecta: shifting paradigms in pathophysiology and care in children. Journal of Pediatric Endocrinology and Metabolism, 38:1-15, Dec 2025. URL: https://doi.org/10.1515/jpem-2024-0512, doi:10.1515/jpem-2024-0512. This article has 4 citations and is from a peer-reviewed journal.