On the 17th of November 2023, OIFE hosted the second Virtual OIFE Investigator Meeting for the OI research community. 273 people from 48 countries signed up and more than 160 individuals attended the online event. Attendees were a mix of health professionals, scientists, OI clinicians and a lower number of representatives from industry and patient groups.

The meeting’s objectives included highlighting recent advances in OI research, providing a collaborative space for researchers in Europe and beyond, attracting fresh talent to European OI research, and offering support to the younger generation of OI researchers. With a focus on fostering a spirit of cooperation and innovation, this meeting aimed to contribute to the growth and development of OI research globally.

European Rare Disease Research Collaboration

Dr. Luca Sangiorgi (ERN BOND coordinator) from Bologna, Italy gave a presentation on possibilities and challenges of European research collaboration. The ERICA (European Rare Disease Research Coordination and Support Action) initiative seeks to enhance collaboration among European Reference Networks (ERNs) for rare diseases. It focuses on improving the quality and impact of clinical trials. One of the tools mentioned was the ERICA PROMs repository.

Challenges include the diverse geographical distribution of Health Care Providers (HCPs) and varying national regulations, for which ERICA has organized webinars that offer insights and tools for clinical trial activities. The last part of the talk was dedicated to the European Rare Diseases Research Alliance (ERDERA) will replace the European Joint Programme for Rare Diseases (EJP RD).

News from basic science 

Screenshot of a male OI-researchers smiling. He is bald and wearing glasses with black rim and a dark shirt.
Roy Morello

Advances in Osteogenesis Imperfecta (OI) research include the development of a new conditional knock-in mouse model for COL1A1, which is tissue-specific. Current mouse models express mutations globally (i.e. in all tissues). This new model will help understand the effect of mutations in one tissue i.e., by only expressing the mutation in the lung (instead of all tissues) it is easier to isolate the impact of the mutation on the lung versus the effects of the mutation on the skeleton.

Screenshot of a woman with curly brown hair and glases wearing earplugs. Background is a photo from Pavia university with arches and statues.
Antonella Forlino

Furthermore, a new potential therapeutic target is endoplasmic reticulum (ER) stress. The endoplasmic reticulum (ER) is important for the proper folding and processing of type I collagen, which is impaired in OI due to the COL1A1/COL1A2 mutation. Targeting the ER stress response through chemical chaperones is thought to improve collagen processing and bone properties in OI mouse models and eventually patients. 4-phenylbutyric acid (4PBA) is a chemical chaperone that is currently being investigated. It is hypothesized to reduce ER stress and improve cell homeostasis.

Techniques to assess bone density, structure, strength, and mobility in OI                                                                   

Profile picture of Enrico SchileoHigh-Resolution Peripheral Quantitative Computed Tomography (HR-pQCT) was introduced as an imaging method that gives information on the bone’s structure and mineral density in the arms and legs. It helps medical professionals estimate the bone’s strength and ability to resist fractures.

The presenter Enrico Schileo from Italy (photo) leads a working group around the use of HR-pQCT OI. If you are interested in participating, please contact him on email enrico.schileo@ior.it

Motion analysis in osteogenesis imperfecta (OI) is a valuable tool for improving clinical decision-making, particularly the assessment and treatment of gait issues. The evaluation of individuals with OI by means of motion analysis and selected functional assessments, along with an accurate biomechanical model of the lower and upper extremities aims to better understand and predict OI disability and improve quality of life.

Bente Langdahl presented plans for a 10-year follow-up study to reassess bone status in adults with OI.

A Danish 10-year follow up study of adults with OI
Plans for a 10-year follow-up study to reassess bone status in adults with OI were announced by Bente Langdahl from Denmark. The planned study aims to reevaluate approximately 80-100 adults with OI, that participated in a clinical trial 10 years ago.

The methods to conduct skeletal studies, reevaluate bone health and identify fractures include: Dual-energy X-ray Absorptiometry (DXA) to measure areal BMD for lumbar spine, hip and the entire body, High-resolution peripheral quantitative computed tomography (HRpQCT) to measure volumetric BMD of the distal radius, distal tibia, and investigate bone architecture, and spine X-rays. Combining data from multiple assessment methods may help better understand fracture risk long-term.

Our new genetic landscape explained by Dimitra Micha in the session about Classification of OI types.

Nosology & Classification – Categorization of OI types

The purpose of nosology (classification of diseases) is to create a common naming system to facilitate diagnosis for the growing number and variety of skeletal phenotypes (clinical manifestations of a disease) with a genetic basis.

The dyadic naming system, which was recently adopted in the 11th revision of the “Nosology of genetic skeletal disorders” is a classification system used in osteogenesis imperfecta (OI) that incorporates both genotype (the underlying genetic mutation) and phenotype (clinical manifestations).

The session started with 3 introductory talks from Valérie Cormier Daire (France), Joan Marini (USA) and Dimitra Micha (The Netherlands) who gave their their thoughts on how a classification system of OI should look like – and whether the genetic mutation or the clinical picture should come first in a dyadic system.

This was followed by a panel debate, where Fleur van Dijk and Lena Lande Wekre joined. There was no consensus reached during this meeting, but all the participant agreed that this is an important discussion and that our goal should be to find a classification system that both clinicians, researchers and people with OI can live with.

Read the whole programme of the 2023 meeting here.