July 13, 2016 — The FNIH Biomarkers Consortium recently released the first study results from the Bone Quality Project, which analyzed bone mineral density (BMD) as a biological marker (biomarker) for predicting hip fractures. These fractures are considered the most serious consequence of osteoporosis, a condition in which the bones weaken or easily break. More than 53 million people in the United States have or are at a high risk for osteoporosis, according to the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS).
The study findings showed that increased hip BMD may be a good indicator that a new drug can decrease an individual’s risk of hip fracture. Therefore, hip BMD might be useful as a biomarker in determining the effectiveness of treatments to reduce hip fractures in patients with osteoporosis.
Chaired by Gayle Lester, Ph.D., program director at NIAMS, the project team includes representation from the U.S. Food and Drug Administration (FDA), academic institutions, the pharmaceutical industry and not-for-profit sector. A main goal of the project is to track the progression of osteoporosis by identifying more precise biomarkers using data from existing academic and clinical trials to pave the way for more effective treatments.
The University of California - San Francisco (UCSF) is leading the research for the project. Principal Investigators include Dennis Black, Ph.D., and Doug Bauer, M.D., from UCSF and Mary Bouxsein, Ph.D., from Harvard Medical School.
In the following Q&A, Dr. Dennis Black discusses the significance of the Bone Quality Project’s first study results.
Q: What were the recent study results and their significance?
A: Our group performed an analysis on data from approximately 73,000 women in 14 clinical trials, where we examined the relationship between the change in total hip BMD and hip fracture. The preliminary analyses indicate that the magnitude of change in total hip BMD with treatment is closely related to hip fracture reduction. Even small increases in total hip BMD resulted in dramatic reduction in hip fracture.
Due to the relatively low rates of hip fracture, clinical trials have become large and expensive to conduct. Innovative solutions are now being created to fulfill the need for better osteoporotic treatments given that large clinical trials are no longer feasible to conduct. Among these solutions is the proposal of using a surrogate biomarker endpoint, such as change in hip BMD, in order to predict the decreased risk of hip fracture.
Q: What are the next steps for the further development of this biomarker?
A: The next steps will be to submit a letter of intent to the FDA to proceed with formal qualification of the biomarker. Once the letter is approved, our group will work on creating a package for submission to the FDA for development and regulatory acceptance, and qualification of BMD for use in drug development. This includes analyzing individual-level study data in hopes that they will strengthen our argument and create guidelines for use of this specific biomarker.
Q: How will the study results affect future clinical trials?
A: The ultimate goal of using a surrogate biomarker will be to decrease the need for hip fracture outcomes in future trials. The Bone Quality Project aims to help facilitate future drug development by having a surrogate measure that could be used to design more efficient randomized clinical trials.
Q: What is unique about the Bone Quality Project?
A: The Bone Quality Project is unique in that we are evaluating osteoporosis biomarkers that are obtained from randomized clinical trials across many different companies to qualify them for use in drug development and patient management. This type of collaboration among government organizations, industry and academia would not have been possible without the public-private partnership model fostered by the FNIH Biomarkers Consortium.
Additionally, no other studies have ever addressed the relationship between changes in BMD and hip fracture reduction.
Q: How do you envision the Bone Quality Project benefiting osteoporosis patients in the long-term?
A: Hip fractures are the most serious consequence of osteoporosis and it is critically important to develop new agents that can reduce their risk. Use of these markers directly addresses this hip fracture risk. Development and use of a surrogate will allow for clinical decision making prior to hip fracture, saving people from pain and suffering.