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成骨不全

Osteogenesis imperfecta

ORPHA:666疾病中国目录 第1批 · 86

定义 英文原文（暂无中文）

A rare, genetic, primary bone dysplasias characterized by increased bone fragility, low bone mass, and susceptibility to bone fractures. The clinical severity is heterogeneous.

别名

Porak和Durante病

基本事实

遗传方式
常染色体显性、常染色体隐性、X 连锁隐性
发病年龄
各年龄段
患病率
1-5 / 10 000

相关基因 28来自下位疾病

Orphanet 未在本条目上直接标注致病基因。下表由本组所属的下位疾病汇总而来，「来源条目」列给出基因实际标注在哪一个 ORPHA 条目上。

基因名称来源条目
ANO5anoctamin 5ORPHA:53697
ATP6V0A2ATPase H+ transporting V0 subunit a2ORPHA:2834
BMP1bone morphogenetic protein 1ORPHA:314029
COL1A1collagen type I alpha 1 chainORPHA:314029
COL1A2collagen type I alpha 2 chainORPHA:314029
CREB3L1cAMP responsive element binding protein 3 like 1ORPHA:216812
CRTAPcartilage associated proteinORPHA:216804
FKBP10FKBP prolyl isomerase 10ORPHA:216820
GORABgolgin, RAB6 interactingORPHA:2078
IFITM5interferon induced transmembrane protein 5ORPHA:216828
LRP5LDL receptor related protein 5ORPHA:2788
MBTPS2membrane bound transcription factor peptidase, site 2ORPHA:216796
MESDmesoderm development LRP chaperoneORPHA:216804
NBASNBAS subunit of NRZ tethering complexORPHA:391677
P3H1prolyl 3-hydroxylase 1ORPHA:216804
P4HBprolyl 4-hydroxylase subunit betaORPHA:216796
POLR3ARNA polymerase III subunit AORPHA:3455
PPIBpeptidylprolyl isomerase BORPHA:216804
PYCR1pyrroline-5-carboxylate reductase 1ORPHA:2078
SEC24DSEC24 homolog D, COPII componentORPHA:216796
SERPINF1serpin family F member 1ORPHA:216820
SERPINH1serpin family H member 1ORPHA:216812
SP7Sp7 transcription factorORPHA:216820
SPARCsecreted protein acidic and cysteine richORPHA:216820
TENT5Aterminal nucleotidyltransferase 5AORPHA:216812
TMEM38Btransmembrane protein 38BORPHA:216820
WNT1Wnt family member 1ORPHA:216820
XYLT2xylosyltransferase 2ORPHA:85194

临床表型 114

极常见 99–80%19

  • 干骺端形态异常 HP:0000944
  • 肋骨形态异常 HP:0000772
  • 牙齿颜色异常 HP:0011073
  • 牙釉质形态异常 HP:0000682
  • 胫骨形态异常 HP:0002992
  • 短头畸形 HP:0000248
  • 龋齿 HP:0000670
  • 凸鼻嵴 HP:0000444
  • 颅骨骨化减少 HP:0004331
  • 骨干发育不全 HP:0005019
  • 步态异常 HP:0001288
  • 听力受损 HP:0000365
  • 胎儿宫内发育迟缓 HP:0001511
  • 巨头畸形 HP:0000256
  • 小下颌 HP:0000347
  • 混合性听力受损 HP:0000410
  • 鸡胸 HP:0000768
  • 枕骨突出 HP:0000269
  • 瘦小肋骨 HP:0000883

常见 79–30%40

  • 心血管系统形态异常 HP:0030680
  • 皮质骨形态异常 HP:0003103
  • 椎体形态异常 HP:0003312
  • 股骨形态异常 HP:0002823
  • 长骨形态异常 HP:0011314
  • 牙列异常 HP:0000164
  • 髋骨形态异常 HP:0003272
  • 焦虑 HP:0000739
  • 双凹椎体 HP:0004586
  • 蓝巩膜 HP:0000592
  • 骨痛 HP:0002653
  • 角膜混浊 HP:0007957
  • 皮肤松弛症 HP:0000973
  • 牙齿错位咬合 HP:0000689
  • 牙本质发育不全 HP:0000703
  • 椎弓膨大 HP:0004621
  • 运动不耐受 HP:0003546
  • 疲乏 HP:0012378
  • 股骨弯曲 HP:0002980
  • 复发性长骨骨折 HP:0003084
  • 膝外翻 HP:0002857
  • 青光眼 HP:0000501
  • 高钙尿症 HP:0002150
  • 多汗症 HP:0000975
  • 骨折易感性增加 HP:0002659
  • 关节过度活动 HP:0001382
  • 关节过度活动 HP:0001382
  • 大囟门 HP:0000239
  • 丧失行走能力 HP:0002505
  • 多发性肋骨骨折 HP:0006640
  • 窄胸 HP:0000774
  • 骨质减少 HP:0000938
  • 骨质疏松 HP:0000939
  • 渐进性听力受损 HP:0001730
  • 复发性骨折 HP:0002757
  • 骨密度降低 HP:0004349
  • 身材矮小 HP:0004322
  • 长骨修长 HP:0003100
  • 椎体压缩性骨折 HP:0002953
  • 视觉障碍 HP:0000505

偶见 29–5%33

  • 心内膜形态异常 HP:0004306
  • 关节疼痛 HP:0002829
  • 长骨弯曲 HP:0006487
  • 瘀斑易感性 HP:0000978
  • 前臂骨间膜钙化 HP:0030267
  • 便秘 HP:0002019
  • 牙齿萌出延迟 HP:0000684
  • 桡骨头脱位 HP:0003083
  • 吞咽困难 HP:0002015
  • 屈曲挛缩 HP:0001371
  • 生长延迟 HP:0001510
  • 增生性愈伤组织形成 HP:0030268
  • 腹股沟疝 HP:0000023
  • 肠梗阻 HP:0005214
  • 脊柱后凸畸形（驼背） HP:0002808
  • 短肢 HP:0002983
  • 中枢神经系统的形态异常 HP:0002011
  • 肾结石 HP:0000787
  • 骨关节炎 HP:0002758
  • 感觉异常 HP:0003401
  • 漏斗胸 HP:0000767
  • 髋臼内陷 HP:0003179
  • 相对大头畸形 HP:0004482
  • 脊柱侧弯 HP:0002650
  • 小于胎龄儿 HP:0001518
  • 躯体感觉异常 HP:0003474
  • 血小板减少症 HP:0001873
  • 三角脸 HP:0000325
  • 三叉神经痛 HP:0100661
  • 脐疝 HP:0001537
  • 巨脑室 HP:0002119
  • 内脏血管瘤病 HP:0100761
  • 缝间骨 HP:0002645

罕见 <4–1%22

  • 主动脉瘤 HP:0004942
  • 主动脉夹层 HP:0002647
  • 主动脉瓣反流 HP:0001659
  • 主动脉根部瘤 HP:0002616
  • 动脉夹层 HP:0005294
  • 共济失调 HP:0001251
  • 颅底凹陷 HP:0012366
  • 脑干受压 HP:0002512
  • 脑出血 HP:0001342
  • 颈椎后凸畸形 HP:0002947
  • 颅神经麻痹 HP:0006824
  • 头痛 HP:0002315
  • 脑积水 HP:0000238
  • 二尖瓣脱垂 HP:0001634
  • 新生儿呼吸窘迫 HP:0002643
  • 非交通性脑积水 HP:0010953
  • 眼球震颤 HP:0000639
  • 肺发育不良 HP:0002089
  • 肢体近端缩短 HP:0008905
  • 脊髓空洞症 HP:0003396
  • 四肢轻瘫 HP:0002273
  • 胸廓发育不全 HP:0005257

近两年的全球研究 2,036L2

2024/10 起在 Europe PMC 检索所得，按发表时间倒序显示最近 20 篇。标题未译成中文——自动翻译需要接入 LLM 服务，尚未引入。

  • 2026-10
    Interpreting romosozumab-associated BMD changes in osteogenesis imperfecta: design, densitometry, and multiplicity
    Osteoporosis international : a journal established as result of cooper · DOI · Europe PMC
  • 2026-10综述开放获取
    Two-Photon Fluorescence and Second-Harmonic Generation Microscopy: Principles and Biomedical Applications
    Journal of biophotonics · DOI · Europe PMC
  • 2026-10
    NonTobacco Nicotine Dependence Is Associated With Increased Fracture Risk in Adolescents and Young Adults
    Journal of orthopaedic trauma · DOI · Europe PMC
  • 2026-09综述
    Pathogenesis and precision management of osteogenesis imperfecta: from genetic mechanisms to novel therapies
    World journal of pediatrics : WJP · DOI · Europe PMC
  • 2026-09
    Evaluating dental developmental abnormalities in osteogenesis imperfecta: associations with timing and cumulative exposure to intravenous pamidronate- a pilot study
    Clinical oral investigations · DOI · Europe PMC
  • 2026-09综述
    Pediatric osteoporosis: a comprehensive imaging-based review of diagnosis, differential diagnosis, and etiology
    Skeletal radiology · DOI · Europe PMC
  • 2026-09开放获取
    Automated GenePy gene-burden computation via a reproducible Nextflow workflow integrated with the Genomics England (GEL) Lifebit platform
    NAR genomics and bioinformatics
  • 2026-09
    In vitro validation of a CRISPR/Cas9 guide RNA targeting COL1A1 gene by cleavage assay
    Methods (San Diego, Calif.) · DOI · Europe PMC
  • 2026-09
    Longitudinal change of bone microarchitecture and fracture risk in adults with osteogenesis imperfecta
    Bone · DOI · Europe PMC
  • 2026-09
    Erratum
    Molecular Syndromology
  • 2026-09
    Skeletal pathologies caused by PLS3 inactivation are predominantly associated with impaired cortical bone integrity
    Journal of bone and mineral research : the official journal of the Ame · DOI · Europe PMC
  • 2026-09综述
    Beyond Density: Fixation Strategies and Healing Paradoxes in Osteogenesis Imperfecta Fractures
    JBJS reviews · DOI · Europe PMC
  • 2026-09开放获取
    Parental needs and experiences with e-Health applications in chronic pediatric care - a scoping review
    BMC pediatrics · DOI · Europe PMC
  • 2026-09开放获取
    The German S3-level guideline for the diagnosis and management of rare dental disorders
    Clinical oral investigations · DOI · Europe PMC
  • 2026-09开放获取
    Pathogenic O-GlcNAc dyshomeostasis is associated with cortical malformations and hyperactivity
    eLife · DOI · Europe PMC
  • 2026-09综述开放获取
    Decoding Skeletal Biology Through Transcriptomics: Insights from Bulk, Single-Cell, Spatial, and Multi-Omics Approaches
    International journal of molecular sciences · DOI · Europe PMC
  • 2026-09开放获取
    Qualitative investigation evaluating Team USA Paralympic athletes: resources and recommendations for enhancing support systems
    BMJ open · DOI · Europe PMC
  • 2026-09开放获取
    Regeneration programs buffer genetic defects in animal development
    PLoS biology · DOI · Europe PMC
  • 2026-09开放获取
    Clinical and genetic spectrum of dual rare genetic diseases revealed by whole-exome sequencing in 14 pediatric patients
    Orphanet journal of rare diseases · DOI · Europe PMC
  • 2026-09开放获取
    BMI, Vitamin D Status, and Biochemical Markers of Mineralization in Children with Low-Energy Fractures: A Prospective Case-Control Study
    Children (Basel, Switzerland) · DOI · Europe PMC

境外已获批用于本病的药物 0L2

欧盟与美国均未检索到已获批用于本病的药物。

尚未获批的在研药物（16 项）

这些药已被欧盟或美国的监管机构认定为罕见病用药（英文 orphan drug designation，中文行业里通称「孤儿药资格」——「孤儿」说的是这类药市场太小、没有厂商愿意认领，不是在说病人）。但这只是一种监管身份：意味着监管机构给予研发上的激励，不代表这个药已被证明有效，也不代表将来一定能上市，绝大多数最终不会成药。列在这里是为了看清有哪些方向正在被尝试。

  • human allogeneic bone-marrow-derived osteoblastic cells欧盟2015-08-10
    Treatment of osteogenesis imperfecta
    官方记录
  • recombinant humanised monoclonal IgG2 lambda antibody against human sc欧盟2016-06-27
    Treatment of osteogenesis imperfecta
    官方记录
  • allogenic fetal mesenchymal stem cells欧盟2021-12-10
    Treatment of osteogenesis imperfecta
    官方记录
  • losartan欧盟2022-06-21
    Treatment of osteogenesis imperfecta
    官方记录
  • Humanised IgG4 bispecific monoclonal antibody against sclerostin and d欧盟2025-06-20
    Treatment of osteogenesis imperfecta
    官方记录
  • cisatracurium besilate欧盟2026-07-28
    Treatment of osteogenesis imperfecta
    官方记录
  • human allogeneic bone marrow derived osteoblastic cells美国2015-11-09
    Treatment of osteogenesis imperfecta.
    官方记录
  • human monoclonal antibody targeting human sclerostin美国2016-02-29
    Treatment of osteogenesis imperfecta.
    官方记录
  • DNA, (Cm-Gm-Gm-Gm-G-T-G-T-G-G-G-T-T-C-G-T-C-G-T-T-A-G-C-T-T-G-A-T-T-T-美国2019-08-19
    Treatment of Osteogenesis Imperfecta
    官方记录
  • romosozumab美国2021-05-10
    Treatment of Osteogenesis Imperfecta
    官方记录
  • allogenic fetal mesenchymal stem cells美国2022-05-06
    Treatment of Osteogenesis Imperfecta
    官方记录
  • anti-human transforming growth factor beta (TGF-Beta) monoclonal antib美国2022-10-15
    Treatment of Osteogenesis Imperfecta
    官方记录
  • A Humanized Bispecific Antibody Neutralizing Both Sclerostin and Dickk美国2022-10-20
    Treatment of Osteogenesis imperfecta (OI)
    官方记录
  • anti-Siglec-15 monoclonal antibody on a human IgG1-Fc-silenced backbon美国2024-05-29
    treatment of osteogenesis imperfecta
    官方记录
  • N-[(2S)-1-[(3aS,6R,6aR)-6-Ethynyl-3-oxohexahydro-2H-furo[3,2-b]pyrrol-美国2025-11-25
    treatment of osteogenesis imperfecta
    官方记录
  • 4-(2-Methylanilidocarbamoyl)-phenylacetyl-L-Citrullyl-L-Glutamyl-L-Ser美国2026-09-21
    treatment of osteogenesis imperfecta
    官方记录

数据来自欧洲药品管理局（EMA）的药品与罕见病用药资格公开导出表，以及美国 FDA 的罕见病用药资格数据库（Orphan Drug Product Designation Database）。两边口径不同：欧盟一侧取的是当前状态仍为「已授权」的药品；美国一侧记录的是「曾获批准」这一事实，FDA 的公开表不追踪药物此后是否退市（例如 Relyvrio 于 2024 年撤市，表中仍记为已获批）。请以官方记录页为准。

在中国开展的临床试验 2L2

按病名在 ClinicalTrials.gov 检索、并校验研究中心含中国大陆而来。登记状态不等于现在真的能入组——务必按 NCT 号到原站核实，并与主治医生商量。

登记为可入组 1

  • 招募中NCT07557446
    A Dose REgimen-Finding Study of AGA2115 in Chinese Patients With Osteogenesis ImpeRfecta (EIR)
    II 期 · 干预性 · 2026/06Angitia Biopharmaceuticals Guangzhou Limited
    中国研究中心 4 个：Beijing、Shanghai、Shenzhen、Suzhou
其他状态的试验（1 项）
  • 进行中·不再招募NCT05972551
    Study to Evaluate Efficacy and Safety of Romosozumab Compared With Bisphosphonates in Children and Adolescents With Osteogenesis Imperfecta
    III 期 · 干预性 · 2024/04/22Amgen
    中国研究中心 8 个：Beijing、Changchun、Chengdu、Jinan、Shanghai、Shenzhen 等 8 地

中国境外的在招试验 18L2

这些试验在中国没有研究中心，通常无法直接报名——入组一般要求在当地居住并接受随访。列在这里是因为它另有用处：看清楚全世界正在试哪些药、做到了哪一期、由谁在做。把药名和 NCT 编号记下来去问主治医生，或据此进一步查该药是否已在境外获批、是否有拓展性用药（expanded access）通道。

法国4美国4意大利4比利时2加拿大2德国1日本1阿根廷1澳大利亚1丹麦1荷兰1英国1

CT.gov 报告命中 18 项，此处取回并展示最近的 15 项。

  • 尚未开始招募NCT05559801
    Mesenchymal Cell Therapy in Osteogenesis Imperfecta (OI)
    I 期、II 期 · 干预性 · 2027/01Emory University
  • 尚未开始招募NCT07666269
    Morphology in Oral Rare Syndromes & Artificial Intelligence for Clinical Diagnosis
    不适用 · 干预性 · 2026/09/01University Hospital, Bordeaux
    法国
  • 尚未开始招募NCT07594639
    GRACE II (General Retrospective Analysis of Commercial Experience With AGN1 LOEP)
    观察性 · 2026/06/01AgNovos Healthcare, LLC
    比利时
  • 招募中NCT07366086
    Pediatric Safety Follow-up Study of Prior Treatment With Romosozumab for Osteogenesis Imperfecta
    III 期 · 干预性 · 2026/03/18Amgen
    德国、日本、美国
  • 招募中NCT07062588
    Osteogenesis Imperfecta Trial of AGA2115 for ADUlts With COL1A1 and/or COL1A2 GeNetic Variations (IDUN)
    II 期 · 干预性 · 2025/12/12Angitia Incorporated Limited
    阿根廷、澳大利亚、加拿大、丹麦、法国、荷兰、英国、美国
  • 招募中NCT07412782
    REMS25: Study on the Use of REMS Technology in Diseases Commonly Associated With Reduced Bone Mineral Density (BMD)
    不适用 · 干预性 · 2025/12/04Meyer Children's Hospital IRCCS
    意大利
  • 尚未开始招募NCT06874166
    Social Cognition in Dystrophinopathies and Neurodevelopmental Disorders
    观察性 · 2025/09IRCCS Eugenio Medea
  • 尚未开始招募NCT07173010
    Pediatric Arthropathy Beyond Inflammation: Clinical Spectrum and Diagnostic Approach at Assiut University Children Hospital
    观察性 · 2025/09Assiut University
  • 招募中NCT07478224
    An Interventional Study to Evaluate the Impact of Blood Flow Restriction Training on Muscle, Bone, and Quality of Life in Adults With Osteogenesis Imperfecta Type I
    不适用 · 干预性 · 2025/08/19University Hospital, Ghent
    比利时
  • 招募中NCT07287241
    Prospective Observational Cohort Study of Cardiac Structure and Function in Children and Adults With Osteogenesis Imperfecta
    观察性 · 2025/06/10Istituto Ortopedico Rizzoli
    意大利
  • 招募中NCT05927389
    Adapted Physical Activity Program (APA) for Effort Rehabilitation of Children and Teenagers With Osteogenesis Imperfecta
    不适用 · 干预性 · 2024/02/26University Hospital, Toulouse
    法国
  • 尚未开始招募NCT05258019
    Site Preservation After Tooth Extraction
    观察性 · 2023/11/01Nanfang Hospital, Southern Medical University
  • 招募中NCT05419960
    Audio-vestibular Evaluation of Children and Young Adults With Osteogenesis Imperfecta
    观察性 · 2022/12/22Assistance Publique - Hôpitaux de Paris
    法国
  • 招募中NCT05464498
    Evaluation of Collagen-based Medical Device Treatment Combined With Physiotherapy in Subjects With Achilles Tendinopathy.
    不适用 · 干预性 · 2022/06/13Guna S.p.a
    意大利
  • 招募中NCT04152551
    Effects of Bisphosphonates on OI-Related Hearing Loss
    IV 期 · 干预性 · 2019/11/02Hospital for Special Surgery, New York
    美国

外部标识与链接

OrphanetOMIM:166200OMIM:166210OMIM:166220MONDO:0019019GARD:1017ICD-10 Q78.0ICD-11 LD24.K0ClinicalTrials.gov 检索

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本页数据来源

  • 疾病定义、同义词、基因、表型、流行病学：Orphanet（CC BY 4.0）
  • 中文病名：Orphanet 中文包，冻结于 2020-06-01
  • 表型中文标签：HPO 简体中文翻译（CHPO 上游成果）