Interview with Dr. Winnie Liu, Oregon Health and Science University (OHSU), Portland, Oregon, USA

Winnie LiuDr. Winnie Liu is an adult endocrinologist and takes care of patients at Oregon Health and Science University (OHSU) located in Portland, Oregon. Her clinical and research interests are metabolic bone disease with a focus on OI after joining the BBDC (Brittle Bone Disease Consortium) as a co-principal investigator.

Who was behind the project and which methods were used?

We are a close-knit team at OHSU including Eric Orwoll, MD, Lindsey Nicol, MD, Melanie Abrahamson-Sommer and Riley Johnson. We also received input from other experts in the OI field. We conducted a thorough PubMed search of studies involving osteo-protective medications in adults with OI.

What was your research project about?

As an adult endocrinologist, I was motivated to understand fracture risks and the effectiveness of bone protective medications in adults with OI. Thus, in this review, we highlighted the elevated fracture risk in adult patients with OI and summarized current knowledge on pharmacologic treatment options for reducing fractures. Based on available data, we provided clinical frameworks for the timing of therapy initiation, medication options and assessment of therapeutic responses. Lastly, we noted significant gaps in knowledge and opportunities for future studies.

What are the existing therapeutic options for fracture risk reduction in adults with OI?

All the medications we currently use to reduce fracture risk in OI individuals were initially developed to treat osteoporosis. There are no FDA-approved bone strengthening medications for OI patients. Oral and intravenous bisphosphonates have been shown to improve BMD in adults with OI and are the most commonly used therapeutic agents; however, conclusive data confirming fracture protection are lacking. Teriparatide, a PTH-analog, appears to increase BMD, but thus far, robust increase in BMD seems to be limited to those with type I OI and fracture risk reduction remains unknown. We also touched on newer agents such as anti-sclerostin antibodies and TGF-beta inhibitors. More research is definitely needed, to further our understanding of these medications.

What is known about side effects (ONJ, atypical femur fractures etc)?

Osteonecrosis of the jaw (ONJ) and atypical fracture of the femur (AFF) are rare but serious complications of bisphosphonate therapy. The true incidence of bisphosphonate-related ONJ in OI adults is unknown, but based on available data, it is unlikely to be significantly higher than that of adults treated with bisphosphonate for osteoporosis. The link between bisphosphate treatment and AFF is difficult to established because AFF that develop in adult and pediatric patients with OI during bisphosphonate treatments may be due to inherent abnormality in bone quality due to OI rather than to bisphosphonate exposure.

What were your most interesting findings?

Our main conclusion is that bisphosphonate remains the mainstay of treatment but there are some promising data on PTH-analogs (teriparatide/abaloparatide). At the same time, it is important to note that bisphosphonates increase BMD, but we don’t necessarily know that an increase in BMD translates into a decrease in fracture risk in adults with OI. We were surprised by the paucity of published data on the use of denosumab in adults with OI. Thus, further research is definitely needed. Additional trials are needed to examine the effectiveness of therapies in reducing fracture risk.

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

The timing and duration of osteo-protective treatment should be individualized and we should pay special attention to older OI adults and postmenopausal OI patients. We should particularly consider treatment when there is a decline in BMD or new fractures. Bisphosphonates remain the mainstay of treatment, but teriparatide and abaloparatide can be considered for patients with type I OI who are intolerant or had inadequate response to bisphosphonate therapy.

How can we achieve more research in adults with OI?

Increasing knowledge of the gap in research involving adult OI is necessary. Close collaboration among clinicians and scientists who study OI are important to direct our research efforts and resources to the most pressing issues identified by individuals living with OI. I also encourage adults with OI to participate in research studies.

Were patients/patient organizations involved in this review? How?

We included a clinical vignette of an OI patient seen in our clinic to illustrate the importance of the questions that our patients have brought to us.

The whole article can be read here (open access).