AAOS Now

Published 7/1/2016
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Amber Blake

Making Old Bones Young Again

Researchers at the University of Toronto have been studying mice in the hopes of gaining a better understanding of how bone ages. According to their most recent study, presented at the 2016 Orthopaedic Research Society (ORS) annual meeting, old mice retain the capacity for bone repair when they are exposed to a circulation of youthful blood. This research may have implications for elderly human patients, in whom fractures are typically slower to heal or may not heal at all, resulting in significant mobility impairments.

"Bone is a remarkable organ in that it has the capacity to regenerate itself," explained Linda Vi, the team's lead researcher. "It is a highly dynamic structure, laying down new bone and removing old bone, in response to changes on the forces applied to them."

The study involved young (age 3 to 4 months) and old (age 18 to 20 months) mice. Old bone marrow—with fractions of young bone marrow cells—had been transplanted into the old mice. Tibia fractures were subsequently produced in all donor mice. Engraftment of young F4/80-postive monocytes/macrophages was shown to improve fracture healing and osteoblast differentiation in the old mice.

"Our study identified that these improvements in fracture repair are derived from a type of immune cell called a macrophage," said Ms. Vi. "We show that different subtypes of macrophages are present within the healing bones of young and old mice and that these young macrophages produce 'youthful factors' that are greatly diminished in the old macrophage population. When old mice were given just these young macrophages, they showed remarkable improvements in both the pace and quality of fracture repair."

Ms. Vi and her team have already begun testing some of the youthful factors identified in their study to learn more about their ability to promote fracture healing in old mice. "The long-term goal of our work," she explained, "is to be able to develop these youthful factors into a potential therapy in the treatment of fracture healing for older individuals."

Ms. Vi's coauthors of "Macrophage Secreted Factors Rejuvenate Fracture Repair" are Gurpreet S. Baht, PhD; Heather Whetstone, MSc; Raymond Poon; Qingxia Wei1; Puvi Nadesan; and Benjamin A. Alman, MD.

Amber Blake is the ORS communications manager. She can be reached at blake@ors.org