BBD Longitudinal Study of Osteogenesis Imperfecta

Rare Diseases Clinical Research Network Brittle Bone Disease Consortium Longitudinal Study of Osteogenesis Imperfecta

Osteogenesis Imperfecta (OI) is a rare disorder of increased bone fragility characterized by fractures with minimal or absent trauma, dentinogenesis imperfecta (DI), and, in adult years, hearing loss. It is seen in both genders and all races. The clinical features of OI represent a continuum varying from perinatal lethality to individuals with severe skeletal deformities, mobility impairments, and very short stature to nearly asymptomatic individuals with a mild predisposition to fractures, normal stature, and normal lifespan. Fractures can occur in any bone, but are most common in the extremities. These disorders can be devastating and progressive and result in deformity, chronic pain, impaired function and loss of quality of life.

The overall goal of this study is to answer specific question about the natural history of brittle bone diseases as defined by molecular etiology and to develop the foundation for prospective clinical studies.

Study Overview

• Status: Recruiting
• Conditions: Osteogenesis Imperfecta

Detailed Description

The purpose of this natural history study is to perform a long-term follow-up of a large group of people with osteogenesis imperfecta (OI). The research aims are:

1. To collect natural history data on all individuals enrolled in this longitudinal study. The cause of the brittle bone disease will be compared with things like severity, various features and response to treatments.
2. To determine how often people with type I OI have vertebral compression fractures of the spine.
3. To determine how often people with OI develop scoliosis (curvature of the spine).
4. To determine how often people with OI have problems with teeth alignment and how dental health impacts a person's quality of life.
5. To determine the effect of pregnancy in women with OI.

There will be a total of 1000 people with OI in this study. Participants will be asked to come in every year if 17Y and younger or every other year if 18Y and older for a total of five years.

The following information will be collected at the study visits:

Birth History and past surgical history, Current medical history, Scoliosis evaluation, Walking ability Questionnaire, Dental Quality of Life Questionnaire, Scoliosis and fractures Quality of Life Questionnaires, Physical development evaluation, Medications Use

The following tests will be performed:

Physical exam, dental exam, lung function test, hearing test, mobility test.

The following X-rays will be taken:

DEXA scan, X-ray of the spine, X-ray of the jaw.

Biospecimen (urine and blood) samples will be collected.

• Study Type: Observational
• Enrollment (Estimated): 1000

Contacts and Locations

• Study Contact: Name: Dianne Nguyen; Phone Number: 713.798.6694; Email: diannen@bcm.edu

Study Locations

• Canada
  • Quebec
    • Montreal, Quebec, Canada, H3G 1A6
      • Recruiting
      • Shriners Hospital for Children
      • Contact: Michaela Durigova; Phone Number: 514-282-7158; Email: mdurigova@shriners.mcgill.ca
      • Principal Investigator: Frank Rauch, MD
      • Sub-Investigator: Francis Glorieux, MD
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85016
      • Recruiting
      • Phoenix Children's Hospital
      • Contact: Isabella Wheeler; Email: iwheeler@phoenixchildrens.com
      • Principal Investigator: Pamela Smith, MD
  • California
    • Los Angeles, California, United States, 90095
      • Recruiting
      • University of California Los Angeles
      • Principal Investigator: Deborah Krakow, MD
      • Contact: Sarah Gaunt; Email: sgaunt@mednet.ucla.edu
  • Delaware
    • Wilmington, Delaware, United States, 19803
      • Recruiting
      • AI duPont Hospital for Children
      • Principal Investigator: Jeanne Franzone, MD
      • Contact: Katie Richard; Phone Number: 302.298.8367; Email: Katherine.Richard@nemours.org
  • District of Columbia
    • Washington, District of Columbia, United States, 21205
      • Recruiting
      • Children's National Medical Center
      • Principal Investigator: Laura Tosi, MD
      • Contact: Andrew Pennington; Phone Number: 202-476-5562; Email: apenningto@childrensnational.org
  • Florida
    • Tampa, Florida, United States, 33620
      • Recruiting
      • University of South Florida
      • Principal Investigator: Danielle Gomez, MD
      • Contact: Elaine Deval; Phone Number: 813-974-0104; Email: edeval@usf.edu
  • Maryland
    • Baltimore, Maryland, United States, 21205
      • Recruiting
      • Kennedy Krieger Institute / Hugo W. Moser Research Institute
      • Principal Investigator: Malinda Wu, MD
      • Contact: Libby Walker; Email: WalkerEl@kennedykrieger.org
  • Nebraska
    • Omaha, Nebraska, United States, 68198
      • Recruiting
      • University of Nebraska Medical Center
      • Principal Investigator: Danita Velasco, MD
      • Contact: Sarah O'Neill; Phone Number: (402) 616-0562; Email: sarah.oneill@unmc.edu
  • New York
    • New York, New York, United States, 10021
      • Recruiting
      • Hospital for Special Surgery
      • Principal Investigator: Cathleen Raggio, MD
      • Contact: Chloe DeRocher; Email: derocherc@hss.edu
  • Oregon
    • Portland, Oregon, United States, 97239
      • Recruiting
      • Oregon Health and Science University
      • Contact: Melanie Abrahamson; Email: abrahamm@ohsu.edu
      • Principal Investigator: Eric Orwoll, MD
  • Texas
    • Houston, Texas, United States, 77030
      • Recruiting
      • Baylor College of Medicine
      • Contact: Dianne Nguyen; Phone Number: 713-798-6694; Email: diannen@bcm.edu
      • Principal Investigator: V.Reid Sutton, MD
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53201
      • Recruiting
      • Shriners Hospital for Children, Chicago / Marquette University
      • Contact: Angela Caudill, MPT; Phone Number: 773-385-5868; Email: acaudill@shrinenet.org
      • Principal Investigator: Karen Kruger, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

Individuals with a diagnosis of Osteogenesis Imperfecta are eligible to enroll in the natural history study.

Description

Natural History Study:

Inclusion Criteria:

• Individuals with OI diagnosed by molecular (DNA) analysis OR
• Individuals whose clinical history and radiographs are highly suggestive of OI, but whose diagnosis has not been verified by biochemical or molecular studies

Exclusion criteria:

• Individuals who are unable to return for their scheduled follow up visits.
• Individuals with skeletal dysplasias other than OI
• Individuals with OI and a second genetic or syndromic diagnosis

Vertebral Compression Fractures component Inclusion criteria

• Patients with nonsense or frameshift mutations in COL1A1 or COL1A2 of any age and clinical features of OI type I.

Exclusion criteria

• Use of a bone-acting treatment agent such as bisphosphonates, calcitonin, calcitriol, fluoride, etc., within one year of enrollment.
• Conditions other than Osteogenesis Imperfecta-HaploInsufficiency (OI-HI) affecting muscle and/or bone development (i.e. cerebral palsy, rickets)
• Nonsense or frame shift mutations in the final coding exons of COL1A1 or COL1A2, as this may not lead to haploinsufficiency.

Scoliosis in OI component:

Inclusion Criteria

• All study participants between the ages of 3 to 17 years OR
• Study participants 18 years and older with scoliosis

Dental and Craniofacial Abnormalities in OI component:

Inclusion Criteria • All subjects aged 3 years and older enrolled in the Longitudinal Study Exclusion Criteria Subjects who refuse the dental examination

Pregnancy in OI component:

Inclusion criteria

• Females of reproductive age with mutations in any known gene causing OI, who are contemplating pregnancy within 5 years of enrollment in the Natural History Study OR Females who are pregnant with available pre-pregnancy BMD (within 5 years prior to the first pregnancy visit).

Exclusion criteria

• Males
• Females who are peri-menopausal or menopausal
• Females who had gestations associated with higher order multiples.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Natural History of OI	The molecular basis of the brittle bone disease will be correlated with phenotype, disease progression and response to current standard of care therapies.	10 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence and progression of scoliosis in OI	Incidence and progression of scoliosis in OI analyzed by subtype and Cobb Angle assessment	10 years
Number Vertebral compression fractures in OI HaploInsufficiency	Number and location of Vertebral compression fractures in OI-HI	10 years
Incidence of Oral and craniofacial anomalies	Incidence and progression of oral and craniofacial anomalies as captured by panorex and dental exam	10 years
Satisfaction of Oral Health 15Y+	Satisfaction of Oral health as measure by the OHIP 20	10 years
Satisfaction of Oral Health 11Y-14Y	Satisfaction of Oral health as measure by the Oral health QOL 11-14Yrs	10 years
Effect of pregnancy in women with OI	Change in Spine, Hip, and radius Bone Mineral Density in pregnant women with OI	10 years

Collaborators and Investigators

• Sponsor: Baylor College of Medicine
• Collaborators: University of South Florida; University of California, Los Angeles; Oregon Health and Science University; Hospital for Special Surgery, New York; Children's National Research Institute; Shriners Hospitals for Children; University of Nebraska; Phoenix Children's Hospital; Hugo W. Moser Research Institute at Kennedy Krieger, Inc.; Marquette University; Alfred I. duPont Hospital for Children
• Investigators: Study Chair: V. Reid Sutton, M.D., Baylor College of Medicine; Study Chair: Frank Rauch, M.D., McGill University

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2015
• Primary Completion (Estimated): August 31, 2030
• Study Completion (Estimated): December 31, 2031

Study Registration Dates

• First Submitted: April 29, 2015
• First Submitted That Met QC Criteria: April 29, 2015
• First Posted (Estimated): May 4, 2015

Study Record Updates

• Last Update Posted (Actual): August 13, 2025
• Last Update Submitted That Met QC Criteria: August 8, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Keywords: Osteogenesis Imperfecta; Collagen; Brittle Bone Disorder; Rare Disease Clinical Research Network; COL1A2
• Additional Relevant MeSH Terms: Bone Diseases; Musculoskeletal Diseases; Genetic Diseases, Inborn; Connective Tissue Diseases; Osteochondrodysplasias; Bone Diseases, Developmental; Collagen Diseases; Osteogenesis Imperfecta
• Other Study ID Numbers: H36165