Research topic: Investigating the effects of bisphenol A (BPA) exposure on skeletal repair
Research results: Understanding of whether BPA exposure leads to abnormal bone formation and calluses during fracture healing, resulting in delayed unions and inferior biomechanical function
Patient care application of results: Methods to screen, diagnose, and treat bony non-unions and possibly pseudoarthritis resulting from BPA exposure, as well an understanding of safe BPA exposure levels
Simplified patient care application: Better treatment methods for fracture patients who have been exposed to BPA, and new preventive health measures that contribute to better bone health for everyone
Does environmental BPA exposure affect fracture healing?
Three-time OREF grant recipient undertakes a novel investigation
Baby bottles, water bottles, canned goods, plastic food containers, compact discs, water supply pipes. These are some of the many ways humans and animals around the globe are exposed to bisphenol A, or BPA, used to manufacture polycarbonate plastics and epoxy resins.
Questions about the health risks of BPA exposure have been surfacing in environmental and mainstream media as well as with research scientists in a range of medical specialties for years. Now, with support from an Orthopaedic Research and Education Foundation (OREF) Resident Clinician Scientist Training Grant, his third OREF grant, Alexander A. Theologis, MD, a fifth-year research resident at the University of California, San Francisco, is pursuing what appears to be a unique study to determine whether exposure to BPA affects skeletal repair. The grant was made possible by the Musculoskeletal Transplant Foundation.
Why BPA matters
BPA is an endocrine-disrupting chemical (EDC). If that sounds serious, it is.
“EDCs alter the physiologic functions of endogenous hormones, particularly estrogen,” explained Dr. Theologis, “They have the potential to affect the development and homeostasis of any organ system regulated by the endocrine system.”
Among scientists, EDCs in general and BPA in particular have raised red flags in both in vitro and in vivo studies of cartilage and bone. Respectively, they have been implicated in altered chondrocyte and osteoblast function, and in abnormal changes in the size and shape of bones in animals.
Virtually everyone could be affected
The potential threat is broad, encompassing people of many races and ethnicities and all ages. BPA exposure starts in the womb and is highest for people in urban communities, and those who live near or work in agricultural and industrialized facilities. In addition, elevated BPA levels have been found in individuals who are economically and educationally disadvantaged.
“Endocrine-disrupting chemicals, particularly BPA, are ubiquitous in our environment and they alter the normal physiologic function of estrogen, which plays an important role in fracture healing,” Dr. Theologis said.
Potential progress on a stubborn front
Despite decades of research, bony non-unions remain challenging for surgeons, patients, and due to their expense, the health care system. Dr. Theologis hopes his study will provide some long-awaited answers.
Endogenous changes in the endocrine system have been established as risk factors for bony non-unions. But how exogenous factors, including endocrine-disrupting chemicals, such as BPA, might contribute remains largely unexplored.
Specifically, Dr. Theologis’ study will evaluate the effects of BPA on skeletal regeneration in a mouse model. The study builds on Dr. Theologis’ previous research on the molecular mechanisms of estrogen in growth plate biology.
Dr. Theologis hypothesizes that subject mice exposed to BPA will exhibit abnormal bone formation following tibial fractures, and will develop fracture calluses that will result in delayed unions and inferior biomechanical function. Results will be compared for three test groups: high, low, and no (control) doses of BPA.
Dr. Theologis and his research team are currently confirming their preliminary results. They believe their study could yield results that lead to the development of methods to screen, diagnose, and treat bony non-unions and possibly pseudoarthritis as well.
Further, findings from this study could result in a new understanding of “safe” BPA exposure levels. Applied narrowly, such an understanding could set new protocols for preparing for surgery following bone fractures. Applied broadly, a redefinition of acceptable BPA exposure might lead to new preventive health measures contributing to better bone health for people of all ages around the globe.
Specialty-wide, the implications are considerable. Patients who have sustained a wide range of orthopaedic trauma as well as osteotomies and fusions throughout the skeletal system stand to benefit, as do their care teams.
OREF funding made it possible
In spite of its promise, without external funding, this potentially groundbreaking study may not have gotten off the ground.
“The focus in the lab in which I work has been on the intrinsic biology of fracture healing, in terms of inflammation and blood supply. Little work has been done on exogenous exposure to chemicals,” Dr. Theologis explained. “Without this grant, I probably would not have been able to start this research.”
As a result of applying for—and securing—three OREF grants, the first while in medical school, Dr. Theologis said each required more of him, and helped advance his training as well as his specialty. “OREF, because of all the different grant opportunities it offers, allows researchers to answer the big questions, the big unknowns in the field of orthopaedics. That’s worth supporting.”