OREF grant recipient undertakes a novel investigation


Published 2/1/2017
Sharon Johnson

Does Environmental BPA Exposure Affect Fracture Healing?

For years, research scientists in a range of medical specialties have raised questions about the health risks of human and animal exposure to bisphenol A (BPA), a chemical used to manufacture polycarbonate plastics and epoxy resins for products such as water bottles, plastic food containers, and water supply pipes. In response, 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.

Why BPA matters
BPA is an endocrine-disrupting chemical (EDC). These chemicals are ubiquitous in our environment, according to Dr. Theologis.

"[EDCs] alter the normal physiologic function of estrogen, which plays an important role in fracture healing," he explained. "They have the potential to affect the development and homeostasis of any organ system regulated by the endocrine system."

EDCs in general, and BPA in particular, have raised red flags in both in vitro and in vivo studies of cartilage and bone. They have been implicated in altered chondrocyte and osteoblast function, and in abnormalities in the size and shape of bones in animals.

The potential threat is broad, encompassing people of all ethnicities and 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.

Potential progress on a stubborn front
Despite decades of research, bony nonunions remain challenging for surgeons, patients, and, due to their expense, the healthcare system. Endogenous changes in the endocrine system have been established as risk factors for bony nonunions. But how exogenous factors, including EDCs 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 his 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.

Broad implications
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 nonunions and possibly pseudoarthroses 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.

Dr. Theologis' work is supported by an Orthopaedic Research and Education Foundation (OREF) Resident Clinician Scientist Training Grant funded by the Musculoskeletal Transplant Foundation.

"The intrinsic biology of fracture healing, in terms of inflammation and blood supply, has been the focus of the lab in which I work," Dr. Theologis explained. "Little work has been done on exogenous exposure to chemicals. Without this grant, I probably would not have been able to start this research."

Sharon Johnson is a contributing writer for OREF. She can be reached at communications@oref.org