Interview with Josephine Tauer, PhD, Basic and translational researcher,
Johannes Kepler University in Linz, Austria

Tell us about you and your work related to OI!

I’m Josephine, a basic and translational researcher specializing in bone diseases. My academic journey began in biotechnology, followed by a PhD in Biomedicine from the Medical University in Dresden, Germany. There I investigated the impact of medical treatments for children with chronic myeloid leukemia on their bone health. After completing my PhD, I became interested in rare bone diseases driven by genetic mutations, leading me to postdoctoral research at the Shriners Hospital in Montreal, Canada.

Over several years, I worked with various mouse and zebrafish models of OI, collaborating with clinician-scientists and researchers who became like a second family to me. In January 2024, I joined Prof. Wolfgang Högler’s team at Johannes Kepler University in Linz, Austria, where I hold a tenure-track assistant professorship in the Department of Pediatrics and Adolescent Medicine. My current research centers on uncovering the mechanisms underlying rare diseases such as OI, hypophosphatasia, but also other rare conditions such as monogenetic epilepsy.

Tell us about the project “Intestinal Adaptation in OI”!

The project “Intestinal Adaptation in OI” began as a side discovery during my work at the Shriners Hospital with Prof. Svetlana Komarova. While studying the effects of a bone-derived hormone called Osteocalcin on metabolism in a specific mouse model of OI (Col1a1Jrt mouse) (Tauer et al. Mol Genet Metab 2021;133(2)), I noticed their intestines were very fragile, which seemed oddly specific to OI.

Searching the literature, I initially found very little information, aside from some general gastrointestinal (GI) complaints. Together with Prof. Komarova, we secured a small developmental grant from the Shriners of North America to explore this further and brought in Yuan K. (Karina) Zhang, at this time a master’s student in Nutrition at McGill University, to contribute. Her results were later presented at the online OIFE Investigator meeting, and Karina moved on to Cornell University for her PhD. However, as translating mouse findings to humans is always uncertain, I was encouraged when the Danish research group led by Lars Folkestad, recently published a study showing increased GI disease risk in people with OI, including peptic ulcers and constipation. They also suggested a link to certain medication use, such as NSAIDs and opioids (Anderesen et al. Calcif Tissue Int. 2025;116(1)).

What was your research project about?

This project examined intestinal characteristics in OI mice. We studied 4-, 8-, and 12-week-old mice on a standard diet, hypothesizing that collagen-I mutations could alter intestinal lining, cell organization, and gut microbiome (the community of bacteria in the intestines) function. We used two different OI mouse models: Col1a1Jrt (COL1A1 mutation) and oim (COL1A2 mutation). Since collagen-I consists of three protein strands originating from 2x COL1A1 gene and 1x COL1A2 gene, different mutations may impact intestinal integrity differently.

However, our study had limitations: we only analyzed young mice (up to 12 weeks), didn’t assess dietary effects or bisphosphonate treatment, focused on severe OI forms, and examined only COL1A1 and COL1A2 mutations, excluding other OI-related genes.

What were your most interesting findings?

Our study found that COL1A1 and COL1A2 mutations in OI impact the intestines in certain ways. While absolute intestinal length was comparable to healthy mice, the relative length (meaning normalized to body weight!) was longer in OI mice. Structurally, the OI intestines appeared similar to controls, but we observed potential functional differences, particularly in permeability, as well as shifts in gut microbiome diversity between the two OI models. These changes could affect nutrient digestion and energy supply. Although both models showed similar structural and bacterial alterations, their distinct microbial profiles may reflect different responses to collagen-I mutations. But further research is needed to determine if these findings apply to humans.

 

In the IMPACT survey gastrointestinal issues came out as the 10th most important issue for adults with OI (with fractures as nr. 13)?
What are your thoughts on this?

I found this result both unexpected and expected. Unexpected because GI issues ranked higher than fractures; yet expected because OI is a connective tissue disorder affecting the extracellular matrix (ECM) in multiple organs. Since collagen-I is present in bones, tendons, the cornea, skin, and intestines, it makes sense that OI impacts more than just the skeleton. Notably, OI mice also show respiratory system changes, suggesting that collagen-I mutations may influence various tissues throughout the body (Baglole et al., Pediatr Res 2018; Dimori et al., J Physiol 2023).

What GI issues can collagen issues (in OI) cause?

As mentioned before, a Danish nationwide register-based cohort study found that individuals with OI have a higher risk of peptic ulcer disease, constipation, hernias (in women), inflammatory bowel diseases, biliary and pancreatic disorders, appendicitis, and unspecified abdominal pain compared to the general population (Andersen et al., Calcif Tissue Int. 2025). These findings align with the role of the ECM in cell function and organ biomechanics, particularly in collagen-I-rich tissues like the intestines. Collagen-I mutations could affect ECM elasticity or intestinal biomechanics, potentially leading to constipation. This, in turn, might trigger local inflammation and alter gut bacteria behavior, contributing to further complications. However, factors such as scoliosis, a small and compressed chest, and reduced muscle strength in OI may also play a role in GI issues.

Can people with OI have lower calcium or D-vitamin due to GI issues? Could weight be affected?

Vitamin D deficiency is a global issue in children (Pilz et al., Nutrients 2022) and is also common in OI, with similar prevalence to the general pediatric population (Mohsenzade et al., BMC Pediatr 2021). Around half of OI patients have vitamin D insufficiency, though most with type I OI maintain adequate levels (Kadhim et al., Pediatr Therapeut 2011). However, we need to keep in mind that serum vitamin D levels are influenced by several factors like age, BMI, ethnicity, and diet (Wilsford et al., J Pediatr Orthop 2013). In our research, we examined gene expression related to vitamin D-dependent calcium absorption but haven’t confirmed our findings yet. While OI mice showed higher duodenal (a key area for nutrient absorption) rupture rates, their intestinal structure and overall absorption capacity appeared normal. Further studies are needed to assess nutrient absorption in OI.

We clearly need more research on GI and OI – but where should we start in your opinion?
We should start with patients and collect this kind of data through rare disease registries like the OI module of EuRRBone within ERN BOND. Understanding their experiences – when and under what conditions symptoms occur, is key. For example, tracking GI pain’s timing, type, and severity in relation to meal composition (e.g., high-fat vs. high-protein diets) and the microbiome could provide valuable insights. Additionally, gathering data on symptom frequency, severity, triggers, and relieving factors may help identify patterns and potential causes.

What is the most important take-home message for clinical work?

I believe we should expand our focus beyond bone health in OI and consider how collagen mutations affect other tissues, such as the intestines. A more comprehensive approach could help manage both skeletal and GI complications. Additionally, nutrition plays a key role in OI care. Personalized dietary recommendations, tailored to individual needs and GI sensitivities, could improve overall health and quality of life. Integrating nutritional strategies into clinical care may help alleviate GI discomfort and enhance treatment outcomes.

Did you have any kind of patient involvement?

As a basic and translational researcher, I don’t interact directly with patients, but I have always collaborated closely with clinician scientists, such as Prof. Frank Rauch in the past and now Prof. Wolfgang Högler and his clinical research team. Here in Linz, together, we support clinical studies that integrate laboratory research, focusing on the discovery of rare bone and growth disorders at the Centre of Growth and Osteology. I believe that for any rare disease, research should begin with deep phenotyping and rare disease registry studies to fully understand all features and morbidities associated with the condition.

Links

• Centre of Growth and Osteology
• JKU Research Lab
• OI module of EuRR Bone (now called EuRREB)

This article was first published in OIFE Magazine 2-2025.