Summary by Ingunn Westerheim, Dr Oliver Semler and Dr Lars Folkestad

The OIF investigator Meeting is normally held in Chicago, but took place online on April 15th 2021. OIF Investigator Meeting The program chair this year was Dr Deborah Krakow who is Professor and Chair of the Department of Obstetrics and Gynecology at UCLA. This year’s program had a clinical focus and not so much on basic research.

Topics included:

• Findings from the Brittle Bone Disorders Consortium (BBDC)
• Orthopedic research – non union fractures
• Cardiovascular and pulmonary health
• Biomarkers in OI-research
• Dental issues
• Mouse Models to study pain as disease outcome
• Patient Centered Outcomes Research (PCOR)

Impact of COVID on mental health

A first presentation was given by Misty Richards from Los Angeles about the impact of the Covid pandemic on mental health in OI. In general, the incidence of depression has increased during the last year. The rate of anxiety disorders tripled, and the prevalence of depressive disorders even quadrupled in the US population. A special problem is that many patients who had mental problems already before the pandemic have stopped their therapy due to lockdowns etc.

Chronic pain as risk factor for depression

Chronic pain is a risk factor for depression, and it was assumed that due to reduced availability of medical treatment and reduced possibilities for physiotherapy or physical training the pain level in persons with OI increased. Additional stressors like fear of fractures and insufficient medical care in case of injury aggravated the risk factors. Therefore there is a recommendation, which is also supported by the OIF to implement mental health strategies in the daily care of people with OI and to focus on additional goals like:

• Minimize fracture risk and especially chronic pain
• Realize and treat mental health co-morbidities early
• Stay in contact with other people in your community and with other OI people
• Prepare for a potential hospital stay and check with your doctor what needs to be “prepared” regarding the pandemic.

Non healing fractures

An orthopedic talk presented by Dr. Spencer focused on the issues of «Non-Union Fractures». Non-union is a failure of bone healing 6-9 months after a fracture or an osteotomy after surgery. Even in a well healing fracture an ongoing remodeling of the bone may take many years before the original structure is re-built by osteoblasts. To decide if a surgical treatment is necessary, it is important if non-union is only a radiographic finding, or if the patients is affected by pain and instability of the extremity. It was also emphasized not to stop bisphosphonate treatment in children due to a non-union, regardless of the reason being an osteotomy or fracture. To prevent non-unions, unstable fracture treatment should be avoided. During and after surgery a good blood supply in the area is required. In case of an asymptomatic non-union which is only detected on radiographs, no surgical intervention or other treatment is necessary. A surgical treatment is only required in cases of severe pain or impaired mobility due to the non-union. During the discussion after the talk, it was stated that very little experience in the use of bone morphogenic protein (BMP) to increase fracture healing in patients with OI is available.

Cardiovascular system

Prof. Judge from University of South Carolina gave a talk about the involvement of the cardiovascular system in OI. The most critical points are valve diseases, dilatations of the aortic root and aneurysms in combination with hypertension. In different studies and case series a moderate higher incidence of insufficiencies of the mitral valve has been detected in up to 7-10% of patients with OI. Therefore, it might be recommended to check cardiac function and aortic root in patients with OI specially when patients have a comorbidity of high blood pressure.

Respiratory study was presented

Preliminary data on a respiratory study was presented. The researchers wanted to investigate if respiratory impairments are directly associated with OI or if these problems are only consequences of scoliosis, chest deformities and impaired cardiac function. They included adults with genetically confirmed OI and performed lung function tests, chest CT, echocardiography, and tests to assess physical function of the probands. The first results strengthen the hypothesis that respiratory problems are intrinsic to OI and are not just a complication of other co-morbidities. The chest-CT showed a thickening of the bronchial wall which needs to be investigated further.

Covid-19 survey

Dr. Laura Tosi gave an update on the Patient Centers Outcome Research (PCOR), where the goal is to have community members active through the whole process from determining research questions, interpreting results and dissemination etc. She praised the OIF for reorganizing their services quickly and for organizing 12 videocalls connected to Covid-19 in 2020, which were shared with the worldwide OI-community on YouTube. She also presented some data from the OIF Covid-19 survey and one of the most worrisome facts was that 50% of people with OI who had Covid-19 reported symptoms longer than 4 weeks. People with OI had also become less active during the lockdown, but the vaccination rate is better in the OI-community than the average US population.

Join the OIF Registry!

Dr Tosi encouraged all people with OI to join the OIF Registry, to make it easier to recruit people to surveys and research. She also stressed that future surveys need to have more diversity and better distribution in age, sex and race. Click here to join: https://www.rarediseasesregistry.org/Registration/Registration/RegStart/9797

Lacks in Research, Knowledge in adults with OI, and treatment methods

The panel discussion at the end included three very different topics. Dr. Charlotte Philips asked if the OIF could play a role in saving the different mouse models of OI and raised the question if there should be OI-research in bigger animals like sheep and dogs.

Dr. Eric Rush was frustrated about the lack of knowledge on challenges of adults with OI after a certain age. There is also a lack of good treatment options to gastrointestinal problems, which he stated was surprisingly common. We also need more knowledge on pain and muscle weakness, which can cause functional limitations.

As the last introduction to a short debate, Dr. Frank Rauch emphasized that new treatment methods need to offer something more than what bisphosphonates can offer today. New drugs need to produce more bone and bone of better quality. And we need to develop better methods of measuring when a treatment is efficient or not.